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  "title": "Brain Read Write: techniques for reading and writing the brain",
  "version": "2026.10.30",
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            "text": "A conservative CBF-response FWHM upper-bound scale is 0.47 mm in cat visual cortex with single-stimulus FAIR perfusion fMRI without differential subtraction. This is slightly overestimated by sampling point spread and nonlinear autocorrelation, and may vary across species, regions, or tasks. In rodents, dynamic ASL after a single 333-μs forelimb stimulus yielded a CBF HRF FWHM of ~1 s at 250-ms TR. ASL can cover the whole brain."
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        "value": "Two-photon calcium imaging is fluorescence microscopy in which a neuron's brightness reports its activity. Activity changes a cell's free calcium, and a genetically encoded sensor brightens when it binds calcium; the laser excites the sensor where two photons are absorbed at once, confining the signal to the focal plane. What it reads is the fluorescence change, an indirect measure from which spikes are inferred. In mouse cortical pyramidal cells, jGCaMP8 resolved spike doublets 20 ms apart using averaged responses with simultaneous electrical recording. Older GCaMP6 variants resolved burst spikes at about 50–150 ms spacing.",
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          "reason": "The specified neuronal calcium-imaging and two-photon fluorescence-microscopy protocols yield calcium-dependent GCaMP brightness and fluorescence emission as readouts, not deliberate neural actuation; no neural-writing output applies."
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          "kind": "minimally_destructive",
          "note": "In mouse cortical two-photon calcium imaging, recording is optical, through a cranial window. The invasive steps are surgery for a steel headplate and a 450 µm glass window over much of the left hemisphere, plus, in viral protocols, AAV injected 250 µm deep into visual cortex. GCaMP6s expression for 1-2 months did not obviously perturb cortical circuits. Over months, a small fraction of highly expressing neurons gained nuclear fluorescence and aberrant responses."
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              "note": "Mesoscope protocol, mouse: transgenic GP5.17 mice express GCaMP6f in a subset of pyramidal neurons; GP4.3 mice express GCaMP6s in the vast majority of pyramidal neurons. Behaving activity imaging uses GP4.3 mice."
            },
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            },
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              "note": "GCaMP6 V1 protocol, mouse: AAV2/1-syn-GCaMP-WPRE injected into visual cortex of C57BL/6J mice (1.5-2 months old) for population imaging; for sparse dendritic labeling, diluted AAV2/1-syn-Cre mixed with high-titer Cre-dependent GCaMP6s virus; injections 30 nL over 5 min at 250 µm depth at two V1 sites."
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              "note": "GCaMP6 V1 protocol, mouse: surgery after 2-4 weeks of expression under isoflurane (3% induction, 1.5-2% during surgery); imaging on a 37°C warm blanket under 0.5% isoflurane with chlorprothixene sedation (20-40 µL at 0.33 mg/ml, i.m.)."
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            },
            {
              "kind": "germline_genetic_engineering",
              "note": "Light-beads protocol, mouse: 6 male and female vGluT1-cre x fl-GCaMP6s (pCAG) mice express GCaMP6s in glutamatergic neurons."
            },
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              "note": "Light-beads protocol, mouse: 3 male and female mice express jGCaMP7f through viral transfection."
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              "note": "Light-beads protocol, mouse: transgenic animals carry large (8 mm diameter) cranial windows."
            },
            {
              "kind": "other",
              "note": "Light-beads protocol, mouse: all animals are head-fixed on a home-built treadmill with a rotation encoder on the rear axle."
            }
          ],
          "note": "Mouse two-photon calcium imaging across three protocols: a mesoscope (2p-RAM) protocol with transgenic GCaMP mice, imaged anesthetized for structural calibration views and behaving on a treadmill for activity; an AAV GCaMP6 V1 protocol imaged under light isoflurane with chlorprothixene sedation; and a light-beads volumetric protocol with head-fixed mice on a treadmill."
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            "text": "Spatially, two-photon imaging is bounded by the excitation point-spread function: for tissue imaging at 920 nm with a 1.0 NA objective it is about 0.35 µm FWHM radially and 0.9 µm axially.\n\nFor volume, the 2p-RAM mesoscope excitation path is modelled as diffraction-limited (Strehl ratio above 0.8) across a cylinder 5 mm in diameter and 1 mm deep at 900–1070 nm excitation, about 1.96 × 10⁻⁸ m³. That figure is the optical scan reach of one design, not an acquired functional volume, not uniform tissue penetration and not a ceiling for all calcium microscopes."
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          "value": {
            "min": 3.5e-7,
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            "note": "Typical two-photon excitation point-spread function for tissue imaging at 920 nm with a 1.0 NA objective: 0.35 µm FWHM radially and 0.9 µm axially.",
            "endpoint": "point_spread",
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              {
                "label": "Axial FWHM, 920 nm, 1.0 NA",
                "min": 9e-7,
                "max": 9e-7,
                "note": "Same excitation point-spread function.",
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        "field_of_view_m3": {
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          "value": {
            "min": 1.9635e-8,
            "max": 1.9635e-8,
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            "note": "In the Zemax-modeled 2p-RAM excitation path, the RF objective, pupil relays 1 to 3 and imaging objective are optimized for diffraction-limited performance, with Strehl ratio above 0.8, across a cylindrical volume 5 mm in diameter and 1 mm deep, at excitation wavelengths of 900 to 1070 nm. Propagation time delay difference is kept below 50 fs rms. The volume is pi*(2.5e-3 m)^2*(1e-3 m) = pi*6.25e-9 m3 ≈ 1.96e-8 m3. This figure is the corrected optical scan reach of this design. It is not an acquired functional volume, not uniform tissue penetration, and not a ceiling for all calcium microscopes. The system is applied to mouse cortical calcium imaging.",
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          "note": "In vivo mouse measurements: ~0.9 um lateral FWHM at 644-844 um depth and ~4.4 um estimated axial resolution at 817-948 um depth."
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          "note": "Seconds per image = 1/8.49 Hz ≈ 0.1178 s (about 117.8 ms). This is the image-output cadence for continuous hippocampal spontaneous-activity recording without frame averaging: 256×256 pixels per frame, 200×200 µm field of view, up to 150 neurons, recorded for up to 48 min.",
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            "text": "An ideal quantum-noise-limited mouse CT model gives a minimum isotropic voxel size of 65 μm at 5 Gy and 1% coefficient of variation; at 0.25 Gy the corresponding size is 135 μm. These are modelled sampling sizes, with potentially lethal dose limiting high-resolution live-animal imaging. Whole-brain coverage is represented by the conventional large-brain volume 1.23358 × 10⁻³ m³; this is a reference anatomical size, not the reconstruction box."
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    {
      "slug": "dbs",
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      "group": {
        "id": "stim-implanted",
        "name": "Implanted & surgical write"
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      "mode": "write",
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      "summary": {
        "value": "Deep brain stimulation is a surgical therapy that stimulates the brain electrically without destroying tissue: an electrode implanted inside the skull, wired to an implanted pulse generator, delivers electrical impulses to a focal brain region. The electric field acts on cell bodies, dendrites, axons and glia, but the clinical effect is attributed mainly to exciting axons, and high-frequency stimulation may block local low-frequency oscillations. Closed-loop versions also read local field potentials, such as subthalamic beta or cortical gamma activity, and use them to trigger or adjust the stimulation.",
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      "description": {
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        "value": {
          "text": "Deep brain stimulation (DBS) is a surgical therapy that stimulates the brain electrically without destroying tissue. An electrode implanted inside the skull is connected by an extension wire to an implanted pulse generator, which delivers adjustable electrical impulses to a focal brain region. It is standard care for Parkinson disease, tremor and dystonia. The electric field acts on cell bodies, dendrites, axons and glia, but the clinical effect is attributed mainly to axonal excitation: axons follow pulse trains near 100 Hz faithfully, and synapses transmit such trains less reliably. High-frequency DBS may act as a local information lesion that blocks low-frequency oscillations with little effect on the wider network. Segmented electrodes steer the current direction. The labelled stimulation range of one FDA-approved DBS pulse generator is 2-255 Hz with pulse widths of 10-450 µs. On-demand stimulation is triggered by an event, such as arm movement in essential tremor or seizure activity in epilepsy. Adaptive stimulation is adjusted continuously by a feedback signal: beta power in the subthalamic nucleus local field potential, or gamma activity from a cortical strip electrode as a marker of dyskinesia. Seizure-triggered closed-loop stimulation is promising and needs further exploration."
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            "id": "https://www.accessdata.fda.gov/cdrh_docs/pdf15/P150031B.pdf",
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        "value": {
          "min": 0.003294,
          "max": 0.005703,
          "unit": "m",
          "note": "Sphere-equivalent diameters, under the stipulation that each modeled VTA is a sphere (d=(6V/pi)^(1/3)), of reported volumes of tissue activated (1.871e-8 to 9.71e-8 m3) in a computational GPi DBS model. The VTA was bounded by the 3D extent of simulated axonal action-potential-initiation sites across tabulated stimulation settings (heterogeneous tissue model; axon grid limited to fibers perpendicular to the lead). The study reportedly attributes underestimated axonal activation to omission of parallel fibers and calls the estimate reasonable. The spherical geometry is a stipulation, not a reported shape.",
          "endpoint": "suprathreshold_extent"
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      "temporal_resolution_s": {
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        "value": {
          "min": 0.00392,
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          "unit": "s",
          "note": "Interval between successive DBS pulses, the reciprocal of the pulse frequency. The shortest pulse intervals occur at the upper end of the labelled frequency range of an FDA-approved DBS pulse generator (2-255 Hz; 1/255 Hz = 3.92 ms) and the 250 Hz maximum of the first dual-channel generator (4 ms). A review also lists frequencies of up to 10,000 Hz among new programming parameters without naming a device, while describing 10-kHz (HF-10) waveforms as a spinal cord stimulation therapy likely to be explored in DBS. Pulse widths: about 0.1 ms conventionally; the labelled range is 10-450 microseconds.",
          "endpoint": "inter_pulse_interval",
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            {
              "label": "255 Hz, top of the labelled 2-255 Hz range of an FDA-approved DBS pulse generator",
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              "label": "250 Hz maximum of the first dual-channel generator",
              "min": 0.004,
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              "note": "1/250 Hz = 4 ms.",
              "endpoint": "inter_pulse_interval"
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              "label": "130 Hz, which the review gives as the value used in most DBS applications",
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              "note": "1/130 Hz, about 7.7 ms; also the maximum of the first implantable pulse generator.",
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            {
              "label": "~100 Hz high-frequency trains",
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              "endpoint": "inter_pulse_interval"
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              "label": "Up to 10,000 Hz, stated by a review as a new programming parameter without a named device",
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              "label": "Labelled pulse width range of the FDA-approved generator",
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              "label": "Conventional pulse width",
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      "field_of_view_m3": {
        "state": "known",
        "value": {
          "min": 1.871e-8,
          "max": 9.71e-8,
          "unit": "m3",
          "note": "Volume of tissue activated (VTA) in a computational GPi DBS model, bounded by the 3D extent of simulated axonal action-potential-initiation sites across tabulated stimulation settings (heterogeneous tissue model, axon grid limited to fibers perpendicular to the lead); the study attributes underestimated axonal activation to omission of parallel fibers and calls the estimate reasonable.",
          "endpoint": "suprathreshold_volume"
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        "node": "01a1511d-423f-7083-b245-2153bee2bebf",
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        "state": "incomplete"
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        "value": {
          "measurands": [
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          "note": "DBS mainly drives axonal excitation via the delivered electric field, since axons follow the pulse train more reliably than synaptic transmission; closed-loop systems also sense local field potentials (e.g. subthalamic-nucleus beta-band or cortical gamma activity) to gate or adapt stimulation."
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        "value": {
          "stimuli": [
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          "note": "DBS mainly drives axonal excitation via the delivered electric field, since axons follow the pulse train more reliably than synaptic transmission; closed-loop systems also sense local field potentials (e.g. subthalamic-nucleus beta-band or cortical gamma activity) to gate or adapt stimulation."
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        "value": {
          "kind": "minimally_destructive",
          "note": "Implantation and chronic lead retention cause incidental local tissue damage (haemorrhage, peri-lead oedema, glial encapsulation, foreign-body giant-cell reactions); infection occurs in 5-10% of chronic cases. DBS itself is described as reversible and adjustable, not destructive by design."
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          "steps": [
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              "kind": "surgery",
              "note": "Implantation of the brain electrode"
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            {
              "kind": "surgery",
              "note": "Implantation of the extension and the implanted pulse generator, possibly in a separate surgery from the electrode"
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          "note": "After implantation, DBS entails ongoing expert multidisciplinary care. MRI is often limited to ≤1.5 T, though 3 T can be feasible. Non-rechargeable pulse generators deplete and require replacement surgery: battery life is about 3–5 years in Parkinson's disease and 1–3 years in dystonia (replacement every 3–4 years is also reported), and it is shorter at higher stimulation intensity. Rechargeable pulse generators exist as an alternative. Infection rates reportedly exceed 20% after three or four replacements."
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                "url": "https://doi.org/10.1038/s41582-018-0128-2"
              },
              {
                "node": "01a054a7-8e14-7c81-a734-74c739f84b17",
                "kind": "doi",
                "id": "10.1159/000537865",
                "url": "https://doi.org/10.1159/000537865"
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          },
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            "value": {
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              "amount_min": 6580.0,
              "amount_max": 100040.0,
              "label": "Total DBS treatment, Japan to USA range"
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                "kind": "doi",
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                "url": "https://doi.org/10.1159/000537865"
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            ]
          },
          {
            "value": {
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              "amount_min": 31526.06,
              "year": 2026,
              "label": "Medicare OPPS 61885 pulse-generator insertion/replacement"
            },
            "node": "01a06f30-de1f-7d23-9f91-6ba143db61aa",
            "sources": [
              {
                "node": "01a05972-2dc8-7091-9c27-760e9af9e164",
                "kind": "url",
                "id": "https://www.cms.gov/files/zip/july-2026-opps-addendum-b.zip",
                "url": "https://www.cms.gov/files/zip/july-2026-opps-addendum-b.zip"
              }
            ]
          },
          {
            "value": {
              "kind": "procedure",
              "currency": "USD",
              "amount_min": 11384.04,
              "year": 2026,
              "label": "Medicare OPPS 61888 neurostimulator generator revision/removal"
            },
            "node": "01a06f30-e55c-71b3-9df5-3e2dc6e4f962",
            "sources": [
              {
                "node": "01a05972-2dc8-7091-9c27-760e9af9e164",
                "kind": "url",
                "id": "https://www.cms.gov/files/zip/july-2026-opps-addendum-b.zip",
                "url": "https://www.cms.gov/files/zip/july-2026-opps-addendum-b.zip"
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            ]
          },
          {
            "value": {
              "kind": "session",
              "currency": "USD",
              "amount_min": 135.93,
              "year": 2026,
              "label": "Medicare OPPS 95970 neurostimulator analysis/programming"
            },
            "node": "01a06f30-ec09-7100-92ca-477804a8cf2b",
            "sources": [
              {
                "node": "01a05972-2dc8-7091-9c27-760e9af9e164",
                "kind": "url",
                "id": "https://www.cms.gov/files/zip/july-2026-opps-addendum-b.zip",
                "url": "https://www.cms.gov/files/zip/july-2026-opps-addendum-b.zip"
              }
            ]
          },
          {
            "value": {
              "kind": "procedure",
              "currency": "USD",
              "amount_min": 2206.46,
              "amount_max": 2217.47,
              "year": 2026,
              "label": "CPT 61867 (Implant neuroelectrode, 090-day global), CY2026 October PFS, facility setting, national unadjusted Medicare physician payment (not a device price or hospital charge), with all GPCIs = 1: facility total RVU 66.06 × CF. PPRRVU2026_Oct_nonQPP.csv (CF 33.4009, nonqualifying APM) = $2,206.46; PPRRVU2026_Oct_QPP.csv (CF 33.5675, qualifying APM) = $2,217.47. USD inferred from CMS, a US federal agency, publishing in $."
            },
            "node": "01a14f3a-33ac-76b3-9a35-8bdebd356148",
            "sources": [
              {
                "node": "01a0590c-4778-7910-af19-5ba8fecce5da",
                "kind": "url",
                "id": "https://www.cms.gov/files/zip/rvu26d-updated-08-26-2026.zip",
                "url": "https://www.cms.gov/files/zip/rvu26d-updated-08-26-2026.zip"
              },
              {
                "node": "01a0590c-53da-7332-b711-3cf640f7b8fd",
                "kind": "url",
                "id": "https://www.cms.gov/newsroom/fact-sheets/calendar-year-cy-2026-medicare-physician-fee-schedule-final-rule-cms-1832-f",
                "url": "https://www.cms.gov/newsroom/fact-sheets/calendar-year-cy-2026-medicare-physician-fee-schedule-final-rule-cms-1832-f"
              }
            ]
          },
          {
            "value": {
              "kind": "procedure",
              "currency": "USD",
              "amount_min": 28465.96,
              "amount_max": 41698.02,
              "year": 2026,
              "label": "FY2026 Medicare IPPS national unadjusted inpatient facility base payment (wage index 1, quality/EHR-compliant operating $6,752.61 + capital $524.15 = $7,276.76, before hospital-specific adjustments) for the hospital stay, not device-only or physician cost: MS-DRG 024 (weight 3.9119) $28,465.96 to MS-DRG 023 (weight 5.7303) $41,698.02. Conditional on the full admission record meeting the official grouping logic. Lead code 00H00MZ alone does not determine assignment. DRG 023 applies with Major Device Implant or Acute Complex CNS PDX plus MCC, or Antineoplastic Implant, or PDX Epilepsy with Neurostimulator. DRG 024 applies with Major Device Implant or Acute Complex CNS PDX and none of MCC, Antineoplastic Implant, or PDX Epilepsy with Neurostimulator. Not a patient-specific guarantee."
            },
            "node": "01a14fd1-e543-7051-ad18-f0853add4a6f",
            "sources": [
              {
                "node": "01a0621b-50cc-7ce1-88cb-1724359ed0c9",
                "kind": "url",
                "id": "https://www.cms.gov/files/zip/fy2026-ipps-fr-table-5.zip",
                "url": "https://www.cms.gov/files/zip/fy2026-ipps-fr-table-5.zip"
              },
              {
                "node": "01a0621b-56ae-7be3-9ea0-daf6600488b3",
                "kind": "url",
                "id": "https://www.cms.gov/files/zip/fy2026-ipps-fr-table-1a-1e.zip",
                "url": "https://www.cms.gov/files/zip/fy2026-ipps-fr-table-1a-1e.zip"
              },
              {
                "node": "01a073e0-1653-7332-9842-e0adb60c71c4",
                "kind": "url",
                "id": "https://www.cms.gov/icd10m/FY2026-fr-v43.1-fullcode-cms/fullcode_cms/P0051.html",
                "url": "https://www.cms.gov/icd10m/FY2026-fr-v43.1-fullcode-cms/fullcode_cms/P0051.html"
              }
            ]
          }
        ]
      },
      "theoretical": {
        "description": {
          "state": "known",
          "value": {
            "text": "Space: a model that approximates the volume of activated tissue as a sphere around one monopolar contact gives radii of 1 mm at 1 V and 5 mm at 10 V across the practically relevant voltage range, so the smallest activated region is about 2 mm across and the largest single-contact volume is about 5.24×10⁻⁷ m³. Segmented leads steer the field horizontally, but at higher amplitudes directionality is lost and shaping is limited to the longitudinal direction. Time: at subthalamic, pallidal and thalamic targets in 17 patients, the directly evoked local response has a 0.56 ms absolute refractory period (paired-pulse ratio below 0.2) and recovers fully by 2.94 ms. Fast corticospinal axons activated by transcranial electrical stimulation have absolute refractory periods of 0.82 ms at high and 1.47 ms at moderate intensity, and the D wave recovers completely by 4 ms."
          },
          "node": "01a15d76-9982-7c82-a29b-661cf435a2d2",
          "sources": [
            {
              "node": "01a054a7-8a6c-7b23-92e0-86c560ffbe44",
              "kind": "doi",
              "id": "10.1038/s41582-020-00426-z",
              "url": "https://doi.org/10.1038/s41582-020-00426-z"
            },
            {
              "node": "01a0e549-a19c-72c3-b92a-c447bb459fda",
              "kind": "doi",
              "id": "10.3174/ajnr.a2906",
              "url": "https://doi.org/10.3174/ajnr.a2906"
            },
            {
              "node": "01a0e804-89a4-7601-8a09-9ffa5ea657ac",
              "kind": "doi",
              "id": "10.1002/acn3.51275",
              "url": "https://doi.org/10.1002/acn3.51275"
            },
            {
              "node": "01a0e806-80e3-7503-a0be-43640e59d508",
              "kind": "doi",
              "id": "10.1016/j.clinph.2004.03.016",
              "url": "https://doi.org/10.1016/j.clinph.2004.03.016"
            },
            {
              "node": "01a0e806-8bbb-7880-be4e-a2b8b12fb328",
              "kind": "doi",
              "id": "10.1016/s1388-2457(01)00461-8",
              "url": "https://doi.org/10.1016/s1388-2457(01)00461-8"
            }
          ]
        },
        "spatial_resolution_m": {
          "state": "known",
          "value": {
            "min": 0.002,
            "max": 0.002,
            "unit": "m",
            "note": "Diameter of the volume of activated tissue around one monopolar DBS contact at the low end of the practically relevant voltage range: a model approximating the VAT as a sphere around the active contact gives a 1 mm radius at 1 V and a 5 mm radius at 10 V (impedances 500-2000 ohm), so the smallest activated region is about 2 x 1 mm = 2 mm across. Stipulation: two contacts activate separate regions when their spheres do not overlap, i.e. at a separation of one diameter. Segmented leads can also steer the field horizontally, but at higher amplitudes directionality is lost and shaping is limited to the longitudinal direction.",
            "endpoint": "suprathreshold_extent",
            "operating_points": [
              {
                "label": "Monopolar contact at 1 V (spherical VAT model)",
                "min": 0.002,
                "max": 0.002,
                "note": "Radius 1 mm.",
                "endpoint": "suprathreshold_extent"
              },
              {
                "label": "Monopolar contact at 10 V (spherical VAT model)",
                "min": 0.01,
                "max": 0.01,
                "note": "Radius 5 mm.",
                "endpoint": "suprathreshold_extent"
              }
            ]
          },
          "node": "01a15d73-f4d3-7652-b7f5-e3b543bde785",
          "sources": [
            {
              "node": "01a054a7-8a6c-7b23-92e0-86c560ffbe44",
              "kind": "doi",
              "id": "10.1038/s41582-020-00426-z",
              "url": "https://doi.org/10.1038/s41582-020-00426-z"
            },
            {
              "node": "01a0e549-a19c-72c3-b92a-c447bb459fda",
              "kind": "doi",
              "id": "10.3174/ajnr.a2906",
              "url": "https://doi.org/10.3174/ajnr.a2906"
            }
          ]
        },
        "temporal_resolution_s": {
          "state": "known",
          "value": {
            "min": 0.00056,
            "max": 0.00056,
            "unit": "s",
            "note": "Refractory intervals for DBS-evoked local responses and corticospinal D-wave axons in human patients, from the DBS absolute refractory period to complete D-wave recovery. The DBS local response most likely represents nonsynaptic, direct activation of local neuronal elements.",
            "endpoint": "inter_pulse_interval",
            "operating_points": [
              {
                "label": "Neural absolute refractory period (measured in DBS-evoked responses)",
                "min": 0.00056,
                "max": 0.00056,
                "note": "Mean 0.00056 s (SD 0.00008 s); 17 human patients; intraoperative DBS recording at subthalamic, pallidal and thalamic targets. Defined as the first interstimulus interval among three consecutive paired-pulse ratios <0.2.",
                "endpoint": "inter_pulse_interval"
              },
              {
                "label": "Neural relative refractory period: full recovery (measured in DBS-evoked responses)",
                "min": 0.00294,
                "max": 0.00294,
                "note": "Mean 0.00294 s (SD 0.00105 s); 17 human patients; intraoperative DBS recording at subthalamic, pallidal and thalamic targets. Defined as the first interstimulus interval among three consecutive paired-pulse ratios >0.98.",
                "endpoint": "inter_pulse_interval"
              },
              {
                "label": "Corticospinal D wave: absolute refractory period at high intensity",
                "min": 0.00082,
                "max": 0.00082,
                "note": "Mean 0.00082 s; 14 human patients undergoing surgical correction of spinal deformities; epidural D-wave recording with paired transcranial electrical stimulation under anesthesia.",
                "endpoint": "inter_pulse_interval"
              },
              {
                "label": "Corticospinal D wave: absolute refractory period at moderate intensity",
                "min": 0.00147,
                "max": 0.00147,
                "note": "Mean 0.00147 s; 14 human patients undergoing surgical correction of spinal deformities; epidural D-wave recording with paired transcranial electrical stimulation under anesthesia.",
                "endpoint": "inter_pulse_interval"
              },
              {
                "label": "Corticospinal D wave: complete recovery",
                "min": 0.004,
                "max": 0.004,
                "note": "0.004 s; human patients at anesthetic depths suppressing indirect activity; epidural D-wave recording with two equal transcranial electrical stimuli. Both D2 amplitude and conduction time recovered completely.",
                "endpoint": "inter_pulse_interval"
              }
            ]
          },
          "node": "01a16d75-aa7c-75c2-9092-6227109eb2e8",
          "sources": [
            {
              "node": "01a0e804-89a4-7601-8a09-9ffa5ea657ac",
              "kind": "doi",
              "id": "10.1002/acn3.51275",
              "url": "https://doi.org/10.1002/acn3.51275"
            },
            {
              "node": "01a0e806-80e3-7503-a0be-43640e59d508",
              "kind": "doi",
              "id": "10.1016/j.clinph.2004.03.016",
              "url": "https://doi.org/10.1016/j.clinph.2004.03.016"
            },
            {
              "node": "01a0e806-8bbb-7880-be4e-a2b8b12fb328",
              "kind": "doi",
              "id": "10.1016/s1388-2457(01)00461-8",
              "url": "https://doi.org/10.1016/s1388-2457(01)00461-8"
            }
          ]
        },
        "field_of_view_m3": {
          "state": "known",
          "value": {
            "min": 5.236e-7,
            "max": 5.236e-7,
            "unit": "m3",
            "note": "Largest volume of activated tissue for one monopolar DBS contact within the practically relevant voltage range of a spherical VAT model: radius 5 mm at 10 V, V = 4/3 x pi x (0.005 m)^3 = 5.236e-7 m3 (about 0.52 cm3). The model approximates the VAT as a sphere around the active contact, assumes monopolar stimulation and covers impedances of 500-2000 ohm and voltages up to 10 V. This is per active contact; it is not a reach over the whole brain.",
            "endpoint": "suprathreshold_volume",
            "operating_points": [
              {
                "label": "One monopolar contact at 1 V (radius 1 mm)",
                "min": 4.189e-9,
                "max": 4.189e-9,
                "note": "4/3 x pi x (0.001 m)^3.",
                "endpoint": "suprathreshold_volume"
              }
            ]
          },
          "node": "01a15d75-3e7b-7831-aaec-d69b80a5eaa9",
          "sources": [
            {
              "node": "01a0e549-a19c-72c3-b92a-c447bb459fda",
              "kind": "doi",
              "id": "10.3174/ajnr.a2906",
              "url": "https://doi.org/10.3174/ajnr.a2906"
            }
          ]
        },
        "field_of_view_neurons": {
          "state": "incomplete"
        }
      }
    },
    {
      "slug": "dce-mri",
      "name": "DCE permeability MRI",
      "group": {
        "id": "mri",
        "name": "MRI"
      },
      "mode": "read",
      "core": false,
      "summary": null,
      "row_node": "01a16632-e747-7242-ae03-56008ee23aa3",
      "description": {
        "state": "incomplete"
      },
      "spatial_resolution_m": {
        "state": "incomplete"
      },
      "temporal_resolution_s": {
        "state": "known",
        "value": {
          "min": 3.5,
          "max": 10.0,
          "unit": "s",
          "note": "Per-volume sampling interval: 3.5-6 s in one protocol; typical brain DCE-MRI volume scan times are 5-10 s."
        },
        "node": "01a090c2-4e16-77e3-a39a-02fa19deea30",
        "sources": [
          {
            "node": "01a05959-1286-71b2-b066-65dbabad0433",
            "kind": "doi",
            "id": "10.3348/kjr.2014.15.5.554",
            "url": "https://doi.org/10.3348/kjr.2014.15.5.554"
          },
          {
            "node": "01a05959-3041-7ac1-a0b2-ebf0d327b228",
            "kind": "doi",
            "id": "10.2214/ajr.12.9543",
            "url": "https://doi.org/10.2214/ajr.12.9543"
          },
          {
            "node": "01a05959-3fa6-7292-acce-0956d0d95670",
            "kind": "doi",
            "id": "10.3389/fnagi.2023.1132077",
            "url": "https://doi.org/10.3389/fnagi.2023.1132077"
          },
          {
            "node": "01a05959-4693-7102-809d-b40d658fbdae",
            "kind": "doi",
            "id": "10.1016/j.neuroimage.2015.10.018",
            "url": "https://doi.org/10.1016/j.neuroimage.2015.10.018"
          }
        ]
      },
      "field_of_view_m3": {
        "state": "incomplete"
      },
      "field_of_view_neurons": {
        "state": "incomplete"
      },
      "measurand": {
        "state": "incomplete"
      },
      "stimulation": {
        "state": "incomplete"
      },
      "destructiveness": {
        "state": "incomplete"
      },
      "preparation": {
        "state": "incomplete"
      },
      "cost": {
        "state": "known",
        "items": [
          {
            "value": {
              "kind": "consumable",
              "currency": "USD",
              "amount_min": 0.262,
              "year": 2026,
              "label": "CMS payment limit, gadobutrol, per 0.1 mL (Jul-Sep 2026)"
            },
            "node": "01a06f31-0104-7203-8268-13d7e744a55f",
            "sources": [
              {
                "node": "01a05959-1a20-70e0-a3cc-13c71888fa92",
                "kind": "doi",
                "id": "10.1007/s00330-025-12306-5",
                "url": "https://doi.org/10.1007/s00330-025-12306-5"
              },
              {
                "node": "01a05975-96a2-78e2-bd98-734b2a85f25b",
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                "url": "https://www.cms.gov/files/zip/july-2026-medicare-part-b-payment-limit-files.zip"
              }
            ]
          },
          {
            "value": {
              "kind": "consumable",
              "currency": "USD",
              "amount_min": 0.09,
              "year": 2026,
              "label": "CMS payment limit, gadoterate meglumine, per 0.1 mL (Jul-Sep 2026)"
            },
            "node": "01a06f31-08bc-7f10-914d-24a2ddd40ea5",
            "sources": [
              {
                "node": "01a05959-1a20-70e0-a3cc-13c71888fa92",
                "kind": "doi",
                "id": "10.1007/s00330-025-12306-5",
                "url": "https://doi.org/10.1007/s00330-025-12306-5"
              },
              {
                "node": "01a05975-96a2-78e2-bd98-734b2a85f25b",
                "kind": "url",
                "id": "https://www.cms.gov/files/zip/july-2026-medicare-part-b-payment-limit-files.zip",
                "url": "https://www.cms.gov/files/zip/july-2026-medicare-part-b-payment-limit-files.zip"
              }
            ]
          }
        ]
      },
      "theoretical": {
        "description": {
          "state": "incomplete"
        },
        "spatial_resolution_m": {
          "state": "incomplete"
        },
        "temporal_resolution_s": {
          "state": "incomplete"
        },
        "field_of_view_m3": {
          "state": "incomplete"
        },
        "field_of_view_neurons": {
          "state": "incomplete"
        }
      }
    },
    {
      "slug": "dcs",
      "name": "Diffuse correlation spectroscopy",
      "group": {
        "id": "optical",
        "name": "Optical & ultrasound (in vivo)"
      },
      "mode": "read",
      "core": false,
      "summary": null,
      "row_node": null,
      "description": {
        "state": "incomplete"
      },
      "spatial_resolution_m": {
        "state": "incomplete"
      },
      "temporal_resolution_s": {
        "state": "incomplete"
      },
      "field_of_view_m3": {
        "state": "incomplete"
      },
      "field_of_view_neurons": {
        "state": "incomplete"
      },
      "measurand": {
        "state": "incomplete"
      },
      "stimulation": {
        "state": "incomplete"
      },
      "destructiveness": {
        "state": "incomplete"
      },
      "preparation": {
        "state": "incomplete"
      },
      "cost": {
        "state": "incomplete"
      },
      "theoretical": {
        "description": {
          "state": "incomplete"
        },
        "spatial_resolution_m": {
          "state": "incomplete"
        },
        "temporal_resolution_s": {
          "state": "incomplete"
        },
        "field_of_view_m3": {
          "state": "incomplete"
        },
        "field_of_view_neurons": {
          "state": "incomplete"
        }
      }
    },
    {
      "slug": "des-esm",
      "name": "Direct electrical stimulation mapping",
      "group": {
        "id": "stim-implanted",
        "name": "Implanted & surgical write"
      },
      "mode": "write",
      "core": true,
      "summary": {
        "value": "Direct electrical stimulation mapping (DES/ESM) is a temporary probe of brain function: brief current is passed through electrodes implanted on or in the brain, or through a handheld wand during surgery. The current acts most readily on axons and can inhibit or excite tissue nearby and at a distance; in a 2020 study of recorded neurons it most often inhibited, with excitation linked to high frequencies and sites near white matter. What is read is the response: movements, sensations or language changes, evoked potentials at other electrodes, and afterdischarges.",
        "node": "01a150eb-e673-7253-84ea-7edaf9d0d2d1",
        "sources": [
          {
            "node": "01a05954-17fc-7ba3-aeb3-c8477ea9de74",
            "kind": "doi",
            "id": "10.3389/fnhum.2020.611291",
            "url": "https://doi.org/10.3389/fnhum.2020.611291"
          },
          {
            "node": "01a05954-1ea9-7381-80b8-d7cddf24c9fa",
            "kind": "doi",
            "id": "10.1093/brain/awab125",
            "url": "https://doi.org/10.1093/brain/awab125"
          },
          {
            "node": "01a05954-272a-7541-a2e0-eae735cf4fa5",
            "kind": "doi",
            "id": "10.3389/fnhum.2020.609188",
            "url": "https://doi.org/10.3389/fnhum.2020.609188"
          },
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      "row_node": "01a16d7b-0291-7960-a386-b42925191d62",
      "description": {
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        "value": {
          "text": "Direct electrical stimulation, also called electrical stimulation mapping (DES/ESM), is transient functional mapping of the brain: small bipolar currents inhibit or excite tissue while the responses are recorded. Extraoperative mapping delivers the current through implanted subdural grids or strips, or through stereo-EEG depth arrays placed through burr holes. Intraoperative mapping can use a handheld wand. Awake craniotomy is used for language mapping. The current acts most readily on axons: the axon initial segment and the nodes of Ranvier are the most excitable elements because they carry the most sodium channels. In quantitative models, high-frequency stimulation selectively activates low-threshold fibers of passage and axon terminals that low-frequency stimulation does not. Effects are both local and distant: stimulation activates sites the stimulated area projects to, in a pattern suggesting monosynaptic transmission, and the most common clinical effect is silencing of those areas. In a 2020 study of recorded neuronal activity, stimulation most often inhibited neurons; excitation most often came with high-frequency stimulation and with sites near white matter. What is read is the functional response: motor, somatosensory and language responses, cortico-cortical evoked potentials at other electrodes and afterdischarge thresholds. Electrocorticography monitors afterdischarges, which can confound localization. Extraoperative mapping uses 50 or 60 Hz trains of 0.2 to 0.3 ms pulses lasting 3 to 5 s, starting at 0.5 to 2 mA and rising by 0.5 to 1 mA until a response, an afterdischarge, a seizure or the device limit, with maxima of 10 to 20 mA for subdural electrodes and 3 to 8 mA for stereo-EEG."
        },
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            "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12096052/"
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            "node": "01a0a01e-c326-74c1-95c4-4aeb147cb984",
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            "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8985164/"
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      "spatial_resolution_m": {
        "state": "known",
        "value": {
          "min": 0.01,
          "max": 0.01,
          "unit": "m",
          "note": "Language mapping is described at approximately 1 cm resolution. With 1 cm bipolar contact spacing, current drops sharply at about 5 mm; this is a current-falloff distance, and stimulated area also depends on applied current.",
          "operating_points": [
            {
              "label": "Bipolar current falloff at 1 cm contact spacing",
              "min": 0.005,
              "max": 0.005,
              "note": "Sharp decline at about 5 mm; not a stated threshold boundary."
            }
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        "state": "known",
        "value": {
          "min": 0.01,
          "max": 0.01,
          "unit": "s",
          "note": "Finest stated pulse interval is 0.01 s at the 100 Hz upper end of the extraoperative ESM frequency range; usual 50–60 Hz gives 0.02–0.0167 s intervals. Train durations are separate operating points: somatosensory/motor 1–2 s, language ≤10 s, extraoperative 3–5 s (overall 2–10 s), and one 50 Hz clinical functional-localization protocol 2–5 s.",
          "endpoint": "inter_pulse_interval",
          "operating_points": [
            {
              "label": "Somatosensory and motor cortex mapping",
              "min": 1.0,
              "max": 2.0,
              "note": "Conventional train duration. Significant impairment of sensation or motor paresis prevents adequate testing within these limits.",
              "endpoint": "session_duration"
            },
            {
              "label": "Language identification",
              "max": 10.0,
              "note": "Conventional train duration ≤10 s; no lower bound given. Speech hesitancy or anomia prevents adequate testing within this limit.",
              "endpoint": "session_duration"
            },
            {
              "label": "Extraoperative ESM (reasonable settings)",
              "min": 3.0,
              "max": 5.0,
              "note": "Reasonable setting 3–5 s; overall range 2–10 s.",
              "endpoint": "session_duration"
            },
            {
              "label": "Clinical functional localization protocol (50 Hz bipolar)",
              "min": 2.0,
              "max": 5.0,
              "note": "Reported trains of 2–5 s in one clinical stimulation protocol, with current increased from 1 mA up to 15 mA.",
              "endpoint": "session_duration"
            },
            {
              "label": "Extraoperative pulse-width range",
              "min": 0.0001,
              "max": 0.001,
              "note": "Reasonable settings 0.2–0.3 ms; overall range 0.1–1 ms.",
              "endpoint": "pulse_width"
            },
            {
              "label": "Clinical 50 Hz pulse interval",
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              "endpoint": "inter_pulse_interval"
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        "state": "known",
        "value": {
          "min": 3.4e-7,
          "max": 3.9e-7,
          "unit": "m3",
          "note": "Comparative model with an arbitrary threshold, not a validated absolute recruitment volume; the specific simulation values are not necessarily clinically applicable. Modeled volume of activation (gray plus white matter) for the standard bipolar ±1 mA configuration: electrode axis perpendicular to the gray matter surface, with the bottom edge of the active source contact at the gray-white boundary. Activation was taken as nodes where the primary eigenvalue of the Hessian of the electric potential (the approximated activating function) exceeded an arbitrary 7,393 V/m2 threshold. That threshold was the mean activating function at about 2.778 mm radial distance in the electrode 091 reference condition. Volumes were 0.34 cm3 (electrode 091) and 0.39 cm3 (electrode 093, 114% of reference); 1 cm3 = 1e-6 m3, so these are 3.4e-7 and 3.9e-7 m3.",
          "endpoint": "suprathreshold_volume",
          "operating_points": [
            {
              "label": "electrode 091",
              "min": 3.4e-7,
              "max": 3.4e-7,
              "note": "0.34 cm3 = 3.4e-7 m3; reference condition (100%).",
              "endpoint": "suprathreshold_volume"
            },
            {
              "label": "electrode 093",
              "min": 3.9e-7,
              "max": 3.9e-7,
              "note": "0.39 cm3 = 3.9e-7 m3; 114% of reference under the same configuration and threshold.",
              "endpoint": "suprathreshold_volume"
            }
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        "sources": [
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            "node": "01a147ff-0f59-7b93-bd39-e11c8b3b2bb5",
            "kind": "url",
            "id": "https://hdl.handle.net/10161/30792",
            "url": "https://hdl.handle.net/10161/30792"
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        ]
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      "field_of_view_neurons": {
        "state": "incomplete"
      },
      "measurand": {
        "state": "known",
        "value": {
          "measurands": [
            "motor responses",
            "somatosensory responses (sensory changes during stimulation)",
            "temporal-lobe language-response thresholds",
            "cortico-cortical evoked potentials (CCEPs) at other electrodes",
            "after-discharge thresholds"
          ],
          "note": "DES/ESM can have local and distant effects and predominantly inhibits activity, while excitation is more associated with high-frequency stimulation and proximity to white matter. Afterdischarges can confound functional localization."
        },
        "node": "01a0e54e-806c-7290-a4e6-f079a2ab6ec1",
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      "stimulation": {
        "state": "known",
        "value": {
          "stimuli": [
            "neuronal excitation and inhibition",
            "local and distant effects",
            "functional-localization interference"
          ],
          "note": "DES/ESM preferentially recruits axonal elements, causing local and distant excitation or inhibition. Recordings most often showed inhibition; high frequency and white-matter proximity favored excitation. Afterdischarges can confound localization."
        },
        "node": "01a0d3b8-7910-7e11-ac4b-88fb7e9d90f3",
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        "state": "known",
        "value": {
          "kind": "minimally_destructive",
          "note": "Implantation causes incidental local damage (craniotomy for subdural grids/strips, burr holes and electrode tracks for SEEG); the stimulation current itself is largely non-injurious when biphasic constant-current, with no light-microscopic structural damage detected after prolonged mapping."
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              "note": "For extraoperative ESM, implant subdural grids/strips by craniotomy or SEEG depth arrays through burr holes; intraoperative ESM may instead use a wand."
            },
            {
              "kind": "other",
              "note": "Use ECoG to monitor for afterdischarges."
            },
            {
              "kind": "anesthesia",
              "note": "Awake craniotomy is used for language DES."
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          "note": "Preparation depends on the ESM setting and approach."
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          {
            "value": {
              "kind": "instrument",
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              "amount_min": 14924.0,
              "year": 2014,
              "label": "VA Palo Alto Ojemann cortical stimulator, obligated 2014"
            },
            "node": "01a073f9-4540-7210-abec-d812cfeadf2f",
            "sources": [
              {
                "node": "01a073f8-a964-75a0-840e-4765ece4f401",
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      },
      "theoretical": {
        "description": {
          "state": "known",
          "value": {
            "text": "Bipolar surface microelectrodes with 40 μm pitch achieved better than 100 μm lateral resolution and depths approaching 300 μm in mice at up to 60 μA. Their charge density exceeded 34,000 μC/cm², above the 30–200 μC/cm² safety limits reported for clinical macroelectrodes. Refractoriness constrains independently evoked electrical responses: human DBS-evoked local responses had mean absolute and full-recovery intervals of 0.56 ms and 2.94 ms, respectively; these responses most likely represent nonsynaptic direct activation. Human corticospinal D-wave absolute refractory intervals were 0.82 ms at high intensity and 1.47 ms at moderate intensity, with complete recovery at 4 ms. These physiological response examples retain their stimulation and recording contexts."
          },
          "node": "01a15f3a-9edc-7572-b166-b10eec4dd682",
          "sources": [
            {
              "node": "01a0e5a6-ad58-7a21-ac4c-7485e7f7fe98",
              "kind": "doi",
              "id": "10.1126/sciadv.abq6354",
              "url": "https://doi.org/10.1126/sciadv.abq6354"
            },
            {
              "node": "01a0e804-89a4-7601-8a09-9ffa5ea657ac",
              "kind": "doi",
              "id": "10.1002/acn3.51275",
              "url": "https://doi.org/10.1002/acn3.51275"
            },
            {
              "node": "01a0e806-80e3-7503-a0be-43640e59d508",
              "kind": "doi",
              "id": "10.1016/j.clinph.2004.03.016",
              "url": "https://doi.org/10.1016/j.clinph.2004.03.016"
            },
            {
              "node": "01a0e806-8bbb-7880-be4e-a2b8b12fb328",
              "kind": "doi",
              "id": "10.1016/s1388-2457(01)00461-8",
              "url": "https://doi.org/10.1016/s1388-2457(01)00461-8"
            }
          ]
        },
        "spatial_resolution_m": {
          "state": "known",
          "value": {
            "max": 0.0001,
            "unit": "m",
            "note": "Lateral resolution better than 100 μm using 40-μm-pitch bipolar surface microelectrodes, reaching depths approaching 300 μm in mice at up to 60 μA. The resulting >34,000 μC/cm² charge density exceeds the 30–200 μC/cm² safety limits observed for clinical macroelectrodes."
          },
          "node": "01a1518c-1a45-70b0-9db5-26eb3e5d7af5",
          "sources": [
            {
              "node": "01a0e5a6-ad58-7a21-ac4c-7485e7f7fe98",
              "kind": "doi",
              "id": "10.1126/sciadv.abq6354",
              "url": "https://doi.org/10.1126/sciadv.abq6354"
            }
          ]
        },
        "temporal_resolution_s": {
          "state": "known",
          "value": {
            "min": 0.00056,
            "max": 0.00056,
            "unit": "s",
            "note": "Refractory intervals for DBS-evoked local responses and corticospinal D-wave axons in human patients, from the DBS absolute refractory period to complete D-wave recovery. The DBS local response most likely represents nonsynaptic, direct activation of local neuronal elements.",
            "endpoint": "inter_pulse_interval",
            "operating_points": [
              {
                "label": "Neural absolute refractory period (measured in DBS-evoked responses)",
                "min": 0.00056,
                "max": 0.00056,
                "note": "Mean 0.00056 s (SD 0.00008 s); 17 human patients; intraoperative DBS recording at subthalamic, pallidal and thalamic targets. Defined as the first interstimulus interval among three consecutive paired-pulse ratios <0.2.",
                "endpoint": "inter_pulse_interval"
              },
              {
                "label": "Neural relative refractory period: full recovery (measured in DBS-evoked responses)",
                "min": 0.00294,
                "max": 0.00294,
                "note": "Mean 0.00294 s (SD 0.00105 s); 17 human patients; intraoperative DBS recording at subthalamic, pallidal and thalamic targets. Defined as the first interstimulus interval among three consecutive paired-pulse ratios >0.98.",
                "endpoint": "inter_pulse_interval"
              },
              {
                "label": "Corticospinal D wave: absolute refractory period at high intensity",
                "min": 0.00082,
                "max": 0.00082,
                "note": "Mean 0.00082 s; 14 human patients undergoing surgical correction of spinal deformities; epidural D-wave recording with paired transcranial electrical stimulation under anesthesia.",
                "endpoint": "inter_pulse_interval"
              },
              {
                "label": "Corticospinal D wave: absolute refractory period at moderate intensity",
                "min": 0.00147,
                "max": 0.00147,
                "note": "Mean 0.00147 s; 14 human patients undergoing surgical correction of spinal deformities; epidural D-wave recording with paired transcranial electrical stimulation under anesthesia.",
                "endpoint": "inter_pulse_interval"
              },
              {
                "label": "Corticospinal D wave: complete recovery",
                "min": 0.004,
                "max": 0.004,
                "note": "0.004 s; human patients at anesthetic depths suppressing indirect activity; epidural D-wave recording with two equal transcranial electrical stimuli. Both D2 amplitude and conduction time recovered completely.",
                "endpoint": "inter_pulse_interval"
              }
            ]
          },
          "node": "01a16d75-aa7c-75c2-9092-6227109eb2e8",
          "sources": [
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              "kind": "doi",
              "id": "10.1002/acn3.51275",
              "url": "https://doi.org/10.1002/acn3.51275"
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              "kind": "doi",
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              "url": "https://doi.org/10.1016/j.clinph.2004.03.016"
            },
            {
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              "kind": "doi",
              "id": "10.1016/s1388-2457(01)00461-8",
              "url": "https://doi.org/10.1016/s1388-2457(01)00461-8"
            }
          ]
        },
        "field_of_view_m3": {
          "state": "incomplete"
        },
        "field_of_view_neurons": {
          "state": "incomplete"
        }
      }
    },
    {
      "slug": "desi-ms",
      "name": "DESI mass-spec imaging",
      "group": {
        "id": "microscopy-exvivo",
        "name": "Microscopy & ex vivo"
      },
      "mode": "read",
      "core": false,
      "summary": null,
      "row_node": null,
      "description": {
        "state": "incomplete"
      },
      "spatial_resolution_m": {
        "state": "incomplete"
      },
      "temporal_resolution_s": {
        "state": "incomplete"
      },
      "field_of_view_m3": {
        "state": "incomplete"
      },
      "field_of_view_neurons": {
        "state": "incomplete"
      },
      "measurand": {
        "state": "incomplete"
      },
      "stimulation": {
        "state": "incomplete"
      },
      "destructiveness": {
        "state": "incomplete"
      },
      "preparation": {
        "state": "incomplete"
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      "cost": {
        "state": "incomplete"
      },
      "theoretical": {
        "description": {
          "state": "incomplete"
        },
        "spatial_resolution_m": {
          "state": "incomplete"
        },
        "temporal_resolution_s": {
          "state": "incomplete"
        },
        "field_of_view_m3": {
          "state": "incomplete"
        },
        "field_of_view_neurons": {
          "state": "incomplete"
        }
      }
    },
    {
      "slug": "dot",
      "name": "Diffuse optical tomography",
      "group": {
        "id": "optical",
        "name": "Optical & ultrasound (in vivo)"
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      "mode": "read",
      "core": false,
      "summary": null,
      "row_node": null,
      "description": {
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        "state": "incomplete"
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      "temporal_resolution_s": {
        "state": "incomplete"
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      "field_of_view_m3": {
        "state": "incomplete"
      },
      "field_of_view_neurons": {
        "state": "incomplete"
      },
      "measurand": {
        "state": "incomplete"
      },
      "stimulation": {
        "state": "incomplete"
      },
      "destructiveness": {
        "state": "incomplete"
      },
      "preparation": {
        "state": "incomplete"
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      "cost": {
        "state": "incomplete"
      },
      "theoretical": {
        "description": {
          "state": "incomplete"
        },
        "spatial_resolution_m": {
          "state": "incomplete"
        },
        "temporal_resolution_s": {
          "state": "incomplete"
        },
        "field_of_view_m3": {
          "state": "incomplete"
        },
        "field_of_view_neurons": {
          "state": "incomplete"
        }
      }
    },
    {
      "slug": "dsa",
      "name": "DSA / catheter angiography",
      "group": {
        "id": "nuclear-xray",
        "name": "Nuclear & X-ray"
      },
      "mode": "read",
      "core": true,
      "summary": {
        "value": "Cerebral digital subtraction angiography is an invasive imaging method that uses ionizing radiation. A contrast dye is injected through a catheter in a large artery, and an image taken before the dye arrives is subtracted from the images that follow, leaving mainly the blood vessels visible. The sequence shows the dye filling the arteries, passing through the capillaries and draining through the veins, at a few frames per second in routine dose-limited practice and up to 60 frames per second in high-speed studies. What it reads is the transit of the dye, an indirect picture of brain blood flow and vascular malformations.",
        "node": "01a1660f-8d7d-7d12-8c26-6b12091ab66e",
        "sources": [
          {
            "node": "01a05959-4d08-7c63-873e-1b03dbbcbe57",
            "kind": "doi",
            "id": "10.1007/978-3-030-87231-1_17",
            "url": "https://doi.org/10.1007/978-3-030-87231-1_17"
          },
          {
            "node": "01a05959-54e6-7b32-aed2-77d6b0835f22",
            "kind": "doi",
            "id": "10.1001/jamanetworkopen.2026.1929",
            "url": "https://doi.org/10.1001/jamanetworkopen.2026.1929"
          },
          {
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            "kind": "doi",
            "id": "10.1007/s00062-023-01273-3",
            "url": "https://doi.org/10.1007/s00062-023-01273-3"
          },
          {
            "node": "01a073fe-b63f-74b2-af15-7b78a0ee82ff",
            "kind": "doi",
            "id": "10.3174/ajnr.A3123",
            "url": "https://doi.org/10.3174/ajnr.A3123"
          },
          {
            "node": "01a0e555-86d9-73b2-97da-4280aa93cd4d",
            "kind": "doi",
            "id": "10.3390/jimaging10100260",
            "url": "https://doi.org/10.3390/jimaging10100260"
          },
          {
            "node": "01a15cb9-ae33-7063-9e40-27a7e6f56cfa",
            "kind": "doi",
            "id": "10.3174/ajnr.A3662",
            "url": "https://doi.org/10.3174/ajnr.A3662"
          }
        ]
      },
      "row_node": "01a16a4a-44c5-7c93-a1a1-8b6bdbddbbd0",
      "description": {
        "state": "known",
        "value": {
          "text": "Cerebral digital subtraction angiography (DSA) is an invasive imaging method that follows an injected contrast agent through the blood vessels of the brain using ionizing radiation. A catheter is advanced into a large artery and a contrast agent is injected through it; one centre's standard protocol uses transfemoral access, and transradial access has gained popularity as an alternative for interventional procedures. A mask image acquired before the contrast arrives is subtracted from the subsequent contrast-enhanced image series, so the images show the vasculature at the site of intervention without other anatomical structures. The sequence shows the contrast progressing from the large artery through smaller arteries and the capillaries, then out through the veins: high-resolution dynamic imaging of arterial filling and venous drainage. A 2021 report described best practice as routinely limiting frame rates to 1-3 frames per second to reduce radiation exposure, with up to 7.5 frames per second in some cases; high-speed clinical DSA has been acquired at 60 frames per second in patients with intracranial aneurysms. Color-coded parametric angiography (quantitative DSA) additionally builds a time-density curve from the same acquisition and extracts time- and attenuation-related parameters from it. What is imaged is the transit of the contrast agent, an indirect representation of cerebral blood flow and of vascular malformations."
        },
        "node": "01a15d78-6b90-7432-9fde-4a57e0e007b5",
        "sources": [
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            "node": "01a05959-4d08-7c63-873e-1b03dbbcbe57",
            "kind": "doi",
            "id": "10.1007/978-3-030-87231-1_17",
            "url": "https://doi.org/10.1007/978-3-030-87231-1_17"
          },
          {
            "node": "01a05959-54e6-7b32-aed2-77d6b0835f22",
            "kind": "doi",
            "id": "10.1001/jamanetworkopen.2026.1929",
            "url": "https://doi.org/10.1001/jamanetworkopen.2026.1929"
          },
          {
            "node": "01a05981-d377-7711-9d1f-66c090a66767",
            "kind": "doi",
            "id": "10.1007/s00062-023-01273-3",
            "url": "https://doi.org/10.1007/s00062-023-01273-3"
          },
          {
            "node": "01a073fe-b63f-74b2-af15-7b78a0ee82ff",
            "kind": "doi",
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            "url": "https://doi.org/10.3174/ajnr.A3123"
          },
          {
            "node": "01a0e555-86d9-73b2-97da-4280aa93cd4d",
            "kind": "doi",
            "id": "10.3390/jimaging10100260",
            "url": "https://doi.org/10.3390/jimaging10100260"
          },
          {
            "node": "01a15cb9-ae33-7063-9e40-27a7e6f56cfa",
            "kind": "doi",
            "id": "10.3174/ajnr.A3662",
            "url": "https://doi.org/10.3174/ajnr.A3662"
          }
        ]
      },
      "spatial_resolution_m": {
        "state": "known",
        "value": {
          "min": 0.000079,
          "max": 0.000079,
          "unit": "m",
          "note": "Limiting resolution of the x-ray detector, expressed as the half-period of the finest resolved line-pair frequency (a limiting resolution, not a point-spread FWHM). A two-mode neurointerventional detector resolves up to 6.3 lp/mm without aliasing in its 76 um pixel high-definition zoom mode (about 79 um) and up to 2.5 lp/mm in its 194 um pixel flat-panel mode (about 0.2 mm); the line-pair object was placed on the detector entrance surface to reduce focal-spot blur, so these are detector-plane figures. The high-definition mode covers fields of 8.5 x 8.5 cm down to 3.8 x 3.8 cm and was used to treat intracranial aneurysms in two patients. Standard flat-panel C-arm systems with 184-197 um pixel pitch measured about 1.8-1.9 cycles/mm at 10% MTF (about 0.26-0.28 mm), and cerebral DSA is reported to provide 0.3 mm pixels.",
          "operating_points": [
            {
              "label": "High-definition zoom mode, 76 um CMOS pixels (detector plane)",
              "min": 0.000079,
              "max": 0.000079,
              "note": "6.3 lp/mm resolved without aliasing; small field of view."
            },
            {
              "label": "Same detector, flat-panel mode, 194 um pixels (detector plane)",
              "min": 0.0002,
              "max": 0.0002,
              "note": "2.5 lp/mm resolved without aliasing."
            },
            {
              "label": "Standard flat-panel C-arms, 184-197 um pitch, 10% MTF",
              "min": 0.00026,
              "max": 0.00028,
              "note": "About 1.8-1.9 cycles/mm."
            },
            {
              "label": "Cerebral DSA pixel size (reported)",
              "min": 0.0003,
              "max": 0.0003,
              "note": "0.3 mm pixels.",
              "endpoint": "sampling"
            }
          ]
        },
        "node": "01a15d74-e8d5-7ca2-9eaf-e912fe3ec71e",
        "sources": [
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            "url": "https://doi.org/10.1007/978-3-030-87231-1_17"
          },
          {
            "node": "01a05977-44de-7791-b782-06b6492dabb0",
            "kind": "doi",
            "id": "10.1002/acm2.13741",
            "url": "https://doi.org/10.1002/acm2.13741"
          },
          {
            "node": "01a05982-651e-7971-b1f3-fd3120e81c4b",
            "kind": "doi",
            "id": "10.1120/jacmp.v17i4.5828",
            "url": "https://doi.org/10.1120/jacmp.v17i4.5828"
          },
          {
            "node": "01a15d5a-cd3b-7091-8127-1f3dab7f4937",
            "kind": "doi",
            "id": "10.1111/jon.12652",
            "url": "https://doi.org/10.1111/jon.12652"
          }
        ]
      },
      "temporal_resolution_s": {
        "state": "known",
        "value": {
          "min": 0.016666666666666666,
          "max": 0.016666666666666666,
          "unit": "s",
          "note": "High-speed clinical DSA acquired at 60 frames/s with a 1024 × 1024 detector matrix in 10-second runs in 22 patients with intracranial aneurysms, using a monoplane Allura FD20 system. The 16.7 ms value is the frame interval.",
          "endpoint": "sample_interval"
        },
        "node": "01a15cbb-8f69-73a2-8ddb-7514eaf651cf",
        "sources": [
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            "url": "https://doi.org/10.3174/ajnr.A3662"
          }
        ]
      },
      "field_of_view_m3": {
        "state": "known",
        "value": {
          "min": 0.00123358,
          "max": 0.00123358,
          "unit": "m3",
          "note": "Whole brain. A routine rotational flat-panel protocol for cerebral blood-volume measurement uses a full-size 30 x 40 cm field for whole-brain measurement. The standard rotational flat-panel C-arm (DynaCT) cylinder, 24 cm diameter x 18.5 cm high (0.00837 m3) includes non-brain tissue.",
          "endpoint": "acquired_volume",
          "operating_points": [
            {
              "label": "Standard rotational flat-panel C-arm (DynaCT) cylinder, 24 cm diameter x 18.5 cm high",
              "min": 0.00837,
              "max": 0.00837,
              "note": "pi x (0.12 m)^2 x 0.185 m; includes non-brain tissue.",
              "endpoint": "acquired_volume"
            }
          ]
        },
        "node": "01a16a21-66a3-70f0-ba1e-9359b0d383fb",
        "sources": [
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            "node": "01a0abb5-4bd2-7671-9359-eff3e4e0e3b3",
            "kind": "doi",
            "id": "10.1093/cercor/bhy109",
            "url": "https://doi.org/10.1093/cercor/bhy109"
          },
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            "node": "01a0c161-4193-7d33-b580-284568b78c46",
            "kind": "url",
            "id": "https://www.siemens-healthineers.com/it/angio/options-and-upgrades/clinical-software-applications/syngo-dynact",
            "url": "https://www.siemens-healthineers.com/it/angio/options-and-upgrades/clinical-software-applications/syngo-dynact"
          },
          {
            "node": "01a0d32b-fe95-7f00-b486-0d5bed7917c3",
            "kind": "doi",
            "id": "10.3174/ajnr.a3822",
            "url": "https://doi.org/10.3174/ajnr.a3822"
          },
          {
            "node": "01a15d48-db35-71f3-af9f-fcf94acaadd3",
            "kind": "agent_knowledge",
            "id": "agent: claude-opus-5-5 61756b511276",
            "url": null
          }
        ]
      },
      "field_of_view_neurons": {
        "state": "incomplete"
      },
      "measurand": {
        "state": "known",
        "value": {
          "measurands": [
            "contrast-agent transit"
          ],
          "note": "Cerebral DSA images the progression of contrast dye injected into a large artery through smaller arteries, capillaries, and veins; this is an indirect representation of cerebral blood flow and vascular malformations."
        },
        "node": "01a0b312-612a-71f0-a253-6abc4eb73266",
        "sources": [
          {
            "node": "01a05959-4d08-7c63-873e-1b03dbbcbe57",
            "kind": "doi",
            "id": "10.1007/978-3-030-87231-1_17",
            "url": "https://doi.org/10.1007/978-3-030-87231-1_17"
          },
          {
            "node": "01a073fe-b63f-74b2-af15-7b78a0ee82ff",
            "kind": "doi",
            "id": "10.3174/ajnr.A3123",
            "url": "https://doi.org/10.3174/ajnr.A3123"
          }
        ]
      },
      "stimulation": {
        "state": "incomplete"
      },
      "destructiveness": {
        "state": "known",
        "value": {
          "kind": "minimally_destructive",
          "note": "Diagnostic catheter DSA is minimally destructive: injury is incidental rather than lesioning by design. Permanent neurological deficit: 3/2,340 (0.13%; mixed cerebral/spinal), 0/1,000, 0/1,715, and 1/2,154 (0.05%). Transient/minor neurological deficit: 3/426 (0.70%), TIA 1/1,715 (0.06%), and 2/2,154 (0.1%). These are subsets of clinical neurological complications; the 16/2,340 (0.68%) total neurological rate includes its 3 permanent cases, but the other 13 are not characterized here. Asymptomatic DWI lesions: 21/333 (6.3%); an imaging endpoint, not a symptomatic deficit. Overall angiographic complications: 19/445 (4.3%) versus 25/413 (6.1%) in TRACE, including/reported with one stroke and one femoral pseudoaneurysm as major events. Separately, asymptomatic technical complications were 2.35%, and nonneurological complications were 9/1,715 (0.52%); their overlap with other endpoints is not quantified. Deaths: none in TRACE and no angiography-caused deaths among 2,340 procedures. Rates from different cohorts and endpoints must not be added."
        },
        "node": "01a0b314-3fbc-72a1-9efb-1b674466ad5d",
        "sources": [
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            "node": "01a05959-54e6-7b32-aed2-77d6b0835f22",
            "kind": "doi",
            "id": "10.1001/jamanetworkopen.2026.1929",
            "url": "https://doi.org/10.1001/jamanetworkopen.2026.1929"
          },
          {
            "node": "01a05981-d377-7711-9d1f-66c090a66767",
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          "steps": [
            {
              "kind": "surgery",
              "note": "Femoral access was predominant. Reported femoral equipment included 4F–5F sheaths with angled or sidewinder catheters and guidewires, or 5F–6F introducer sheaths; another protocol used a 5F sheath and primarily a 5F single-curve catheter."
            },
            {
              "kind": "surgery",
              "note": "For the described transradial protocol specifically, the right radial artery was punctured by the Seldinger method after 2% lidocaine; wire advancement was fluoroscopically observed, a 16-cm 6F hydrophilic sheath was inserted, and nitroglycerin, heparin, and verapamil were infused through it. Brachial access was also reported, without technical details."
            },
            {
              "kind": "contrast_agent",
              "note": "Reported agents were manually injected non-ionic Solutrast 300 mg/mL and iopamidol."
            },
            {
              "kind": "anesthesia",
              "note": "One series used 1% lidocaine at the puncture site for all procedures. Conscious sedation was given only when necessary, using optional IV midazolam 1–2 mg and/or fentanyl 25–50 µg. General anesthesia was specified for spinal, not cerebral, angiography."
            }
          ],
          "note": "Reported cerebral DSA uses femoral, radial, or rarely brachial arterial access with a sheath/catheter, contrast medium, puncture-site lidocaine, and optional conscious sedation; equipment and radial adjuncts vary."
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            "node": "01a05973-78e8-7653-9384-a323461661f4",
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            "id": "10.3389/fneur.2025.1688623",
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            ]
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        ]
      },
      "theoretical": {
        "description": {
          "state": "known",
          "value": {
            "text": "DSA (digital subtraction angiography): Field of view: a routine rotational flat-panel cerebral blood-volume protocol uses a full 30 x 40 cm field that covers the whole brain. Temporal: a 1000 fps CdTe photon-counting detector on a commercial c-arm gives a 0.001 s frame interval. This was shown pre-clinically in in-vivo rabbit aneurysm models, where detailed flow could be visualized. It is a demonstration, not a physical bound."
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        "temporal_resolution_s": {
          "state": "known",
          "value": {
            "min": 0.001,
            "max": 0.001,
            "unit": "s",
            "note": "A 1000 fps CdTe photon-counting detector (Aries, Varex), used with a commercial x-ray c-arm system in pre-clinical in-vivo rabbit aneurysm models, gives a 0.001 s frame period; detailed flow can be visualized.",
            "endpoint": "sample_interval"
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        "field_of_view_m3": {
          "state": "known",
          "value": {
            "min": 0.00123358,
            "max": 0.00123358,
            "unit": "m3",
            "note": "Whole brain. A routine rotational flat-panel protocol for cerebral blood-volume measurement uses a full-size 30 x 40 cm field for whole-brain measurement. ",
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    {
      "slug": "dsc-mri",
      "name": "DSC perfusion MRI",
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        "id": "mri",
        "name": "MRI"
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        "value": {
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          "max": 0.005,
          "unit": "m",
          "note": "1-3 mm in-plane (128x128 over a 220 mm FOV is ~1.7 mm) and 3-5 mm through-plane slice thickness."
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        "node": "01a06f31-54db-7201-8e56-7436eb7ffba2",
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            "node": "01a05959-1a20-70e0-a3cc-13c71888fa92",
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            "kind": "doi",
            "id": "10.1016/j.neuroimage.2018.04.069",
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        "value": {
          "max": 1.5,
          "unit": "s",
          "note": "Recommended temporal resolution for single-echo DSC-MRI relative quantification: no slower than 1.5 s."
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            "id": "10.3348/kjr.2014.15.5.554",
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            "id": "10.3174/ajnr.a4341",
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              "label": "CMS payment limit, gadobutrol, per 0.1 mL"
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              "label": "CMS payment limit, unspecified gadolinium-based agent, per mL"
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        "name": "MRI"
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      "core": true,
      "summary": {
        "value": "Diffusion tensor imaging is an MRI method that measures how water diffuses in brain tissue. Diffusion-encoding magnetic field gradients make the scan sensitive to diffusion along at least six directions, and a tensor fitted in each voxel gives the overall diffusion rate and how strongly diffusion prefers one direction. This is an indirect proxy for tissue microstructure, not neural activity; white-matter anisotropy is attributed mainly to cell membranes, with contributions from myelin and axon packing. Tractography uses the data to estimate the paths of white-matter pathways.",
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            "id": "10.1016/j.nec.2010.12.004",
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            "kind": "doi",
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            "node": "01a054bf-93cf-70e2-85ef-6bdd9cedaacd",
            "kind": "doi",
            "id": "10.1016/j.neuroimage.2012.03.072",
            "url": "https://doi.org/10.1016/j.neuroimage.2012.03.072"
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      "row_node": "01a16ca8-ff07-7930-af2b-f0261fffeb2d",
      "description": {
        "state": "known",
        "value": {
          "text": "Diffusion MRI is magnetic resonance imaging that measures the diffusion of water molecules in tissue. Diffusion-encoding gradients are applied during the scan. For diffusion tensor imaging (DTI) the standard setting is a diffusion weighting of b = 1000 s/mm² along at least six non-collinear directions, plus one minimally T2-weighted image at b = 0. The measured quantity is the water diffusion coefficient, in mm²/s. No concentration gradient is present, so this is self-diffusion. Fitting a tensor in each voxel gives an indirect measure of how fast and in which direction water diffuses. Mean diffusivity (MD), also called the apparent diffusion coefficient (ADC), is the overall diffusion rate. Fractional anisotropy (FA) is the directional preference of diffusion. Axial diffusivity is the rate along the main axis of diffusion, and radial diffusivity is the rate across it. In the white matter of the brain, diffusion anisotropy is caused mainly by cellular membranes, with some contribution from myelination and the packing of the axons. Tractography is a computational reconstruction method that uses the diffusion-weighted data to estimate the trajectories of white-matter pathways in vivo and to infer the structural connectome. Methods beyond DTI generally use a higher b-value than 1000 s/mm², or several b-values acquired as multiple shells."
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            "url": "https://doi.org/10.1016/j.nec.2010.12.004"
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      "spatial_resolution_m": {
        "state": "known",
        "value": {
          "min": 0.0015,
          "max": 0.0015,
          "unit": "m",
          "note": "Modelled effective resolution of 1.5 mm: nominal readout sampling was selected using simulated PSF FWHM in the phase-encoding direction to match this effective scale for human whole-brain scans. This is a model tied to an acquisition, not a directly measured in-vivo PSF or a universal DWI limit.",
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          "operating_points": [
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              "min": 0.00076,
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              "note": "Nominal isotropic voxel edge lengths reported for diffusion MRI span 760 μm to 2.5 mm. The 760 μm figure is an in vivo human whole-brain acquisition using a gSlider-SMS protocol, designed for high SNR, low reconstruction error, limited distortion and blurring, and tolerable scan time. Its voxel volume is described as 7.7 times smaller than conventional acquisition at ~1.5 mm. Other reported diffusion MRI voxel sizes are 2 mm (NODDI) and 2.5 mm (typical). For context, axon diameters are 0.2–20 μm, so millimeter-scale voxels may contain hundreds of thousands of axons in complex configurations.",
              "endpoint": "sampling"
            },
            {
              "label": "Whole-brain submillimeter gSlider-SMS acquisition (in vivo human)",
              "min": 0.00076,
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              "note": "760 μm isotropic nominal voxel; volume 7.7 times smaller than ~1.5 mm conventional voxels.",
              "endpoint": "sampling"
            },
            {
              "label": "Conventional dMRI acquisition",
              "min": 0.0015,
              "max": 0.0015,
              "note": "Approximately 1.5 mm isotropic nominal voxel.",
              "endpoint": "sampling"
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            {
              "label": "NODDI",
              "min": 0.002,
              "max": 0.002,
              "note": "2 mm isotropic nominal voxel.",
              "endpoint": "sampling"
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            {
              "label": "Typical diffusion MRI",
              "min": 0.0025,
              "max": 0.0025,
              "note": "2.5 mm isotropic nominal voxel.",
              "endpoint": "sampling"
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        "value": {
          "text": "Electrocorticography (ECoG), or subdural recording, is the recording of neural activity with electrode arrays placed directly on the surface of the cerebral cortex, typically through a craniotomy and without crossing the pia. It is invasive. It measures cortical local field potentials, the averaged activity of many neurons, rather than unit spikes; action potentials have, however, been reported from the cortical surface with electrodes at 30-micron spacing in rodents and humans. Mapping and brain-computer interfaces chiefly use the amplitude or power of the high-gamma band, about 70 to 175 Hz, sometimes together with low-frequency signals. Clinical high-density subdural recording is performed during the invasive work-up for epilepsy surgery, which requires informed consent and subdural access, typically through a large craniotomy. Fully implantable neuromodulatory systems have typically relied on ECoG because its signals have lower data-transmission demands. ECoG recordings are stable over the long term, with little need for recalibration."
        },
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            "url": "https://doi.org/10.1007/s00415-024-12604-w"
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            "node": "01a0548f-a9d7-7951-9170-db3390bd796a",
            "kind": "doi",
            "id": "10.1038/nature11911",
            "url": "https://doi.org/10.1038/nature11911"
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            "node": "01a0548f-b1f4-7b03-96bb-50e48fa36f90",
            "kind": "doi",
            "id": "10.1038/s41586-023-06443-4",
            "url": "https://doi.org/10.1038/s41586-023-06443-4"
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            "node": "01a0548f-b6fa-7240-9b54-db4fb4d6e978",
            "kind": "doi",
            "id": "10.1056/NEJMoa1608085",
            "url": "https://doi.org/10.1056/NEJMoa1608085"
          },
          {
            "node": "01a0548f-bb3f-72e3-9381-d4f2f8cefe28",
            "kind": "doi",
            "id": "10.1056/NEJMoa2027540",
            "url": "https://doi.org/10.1056/NEJMoa2027540"
          },
          {
            "node": "01a0548f-bf3f-7700-ae24-d3c252754175",
            "kind": "doi",
            "id": "10.3389/fneng.2010.00009",
            "url": "https://doi.org/10.3389/fneng.2010.00009"
          },
          {
            "node": "01a054ac-ee51-7d02-8b42-5d19746edceb",
            "kind": "doi",
            "id": "10.1016/j.neuron.2015.03.037",
            "url": "https://doi.org/10.1016/j.neuron.2015.03.037"
          }
        ]
      },
      "spatial_resolution_m": {
        "state": "known",
        "value": {
          "min": 0.001,
          "max": 0.001,
          "unit": "m",
          "note": "Reported spatial resolution of human intraoperative ECoG mapping with thin-film grids of 30 um platinum-nanorod contacts at 1 mm pitch: the spread of epileptic discharges was identified at 1 mm spatial resolution and the curvilinear M1-S1 functional boundary at millimetre scale. The same grid family was built at pitches down to 200 um for human mapping and 150 um for rodents, where sub-millimetre functional organization of rat barrel cortex was resolved. With conventional contacts, the measured cortical spread of a 2.3 mm diameter ECoG electrode is an SD of about 1.5 mm (2 SD about 3 mm), 30-150 Hz signals are largely uncorrelated at 4 mm spacing, and clinical grids sample at about 1 cm.",
          "operating_points": [
            {
              "label": "Rat barrel cortex, 150 um pitch thin-film grid",
              "max": 0.001,
              "note": "Sub-millimetre functional organization resolved."
            },
            {
              "label": "2.3 mm macro contact, measured cortical spread (monkey primary visual cortex)",
              "min": 0.003,
              "max": 0.003,
              "note": "Spread SD about 1.5 mm; 2 SD about 3 mm (a spread width, not a two-source separation)."
            },
            {
              "label": "30-150 Hz decorrelation distance",
              "min": 0.004,
              "max": 0.004,
              "note": "Signals largely uncorrelated at 4 mm spacing."
            },
            {
              "label": "Clinical grids",
              "min": 0.01,
              "max": 0.01,
              "note": "About 1 cm contact spacing with 2-3 mm contacts.",
              "endpoint": "sampling"
            }
          ]
        },
        "node": "01a15d61-a022-7d82-843c-15a5e4bc5ce8",
        "sources": [
          {
            "node": "01a054ac-ee51-7d02-8b42-5d19746edceb",
            "kind": "doi",
            "id": "10.1016/j.neuron.2015.03.037",
            "url": "https://doi.org/10.1016/j.neuron.2015.03.037"
          },
          {
            "node": "01a05944-8d8b-74d1-a1db-6cad9812287f",
            "kind": "doi",
            "id": "10.1088/1741-2560/13/5/056013",
            "url": "https://doi.org/10.1088/1741-2560/13/5/056013"
          },
          {
            "node": "01a07fb0-f686-7260-a39d-96807e7ec6d2",
            "kind": "doi",
            "id": "10.1126/scitranslmed.abj1441",
            "url": "https://doi.org/10.1126/scitranslmed.abj1441"
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          {
            "node": "01a0abbb-ce8a-7851-bac8-587444e8d878",
            "kind": "doi",
            "id": "10.1523/jneurosci.2917-18.2019",
            "url": "https://doi.org/10.1523/jneurosci.2917-18.2019"
          }
        ]
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        "state": "known",
        "value": {
          "min": 0.002,
          "max": 0.004,
          "unit": "s",
          "note": "In this timing model, define dt = 1/B and set B equal to the captured neural band upper edge as an explicit modeling assumption. The resulting proxy is not measured two-event timing precision. Human subdural ECoG recorded on a high-density 8x8 subdural grid (contacts of 1.08 mm^2 surface area, 3 mm center-to-center pitch) in eight subjects captured high-frequency oscillations in two bands. The ripple band (80–250 Hz) gives dt ~ 1/250 Hz = 4 ms. The fast-ripple band (250–500 Hz) gives dt ~ 1/500 Hz = 2 ms. The smallest electrodes recorded more fast ripples than ripples. These reciprocal-bandwidth scales are not directly measured timing precision.",
          "endpoint": "recoverable_timing",
          "operating_points": [
            {
              "label": "Ripple band (80–250 Hz), HD 8x8 grid, 1.08 mm^2 contacts",
              "min": 0.004,
              "max": 0.004,
              "note": "B = 250 Hz, the band's upper edge; dt ~ 1/250 Hz = 4 ms.",
              "endpoint": "recoverable_timing"
            },
            {
              "label": "Fast-ripple band (250–500 Hz), HD 8x8 grid, 1.08 mm^2 contacts",
              "min": 0.002,
              "max": 0.002,
              "note": "B = 500 Hz, the band's upper edge; dt ~ 1/500 Hz = 2 ms. The smallest electrodes recorded more fast ripples than ripples.",
              "endpoint": "recoverable_timing"
            }
          ]
        },
        "node": "01a16a36-9b7b-7ca3-acdb-eab6ba279625",
        "sources": [
          {
            "node": "01a0e8f5-b63c-7f93-9640-271392ec1157",
            "kind": "doi",
            "id": "10.1109/tbme.2024.3416440",
            "url": "https://doi.org/10.1109/tbme.2024.3416440"
          }
        ]
      },
      "field_of_view_m3": {
        "state": "known",
        "value": {
          "min": 1.859e-6,
          "max": 4.601e-6,
          "unit": "m3",
          "note": "Modeled total gray-matter volume recorded by each SDE implant. A 2.5 mm radius and half-sphere model was used for SDE contacts. The mask included cerebral cortex, amygdala, and hippocampus from FreeSurfer parcellations; totals summed overlapping voxels between the recording-volume mask and gray-matter parcellation.",
          "endpoint": "sensing_envelope",
          "operating_points": [
            {
              "label": "SDE subject 1",
              "min": 3.384e-6,
              "max": 3.384e-6,
              "note": "Modeled montage coverage.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "SDE subject 2",
              "min": 2.181e-6,
              "max": 2.181e-6,
              "note": "Modeled montage coverage.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "SDE subject 3",
              "min": 4.601e-6,
              "max": 4.601e-6,
              "note": "Modeled montage coverage.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "SDE subject 4",
              "min": 3.509e-6,
              "max": 3.509e-6,
              "note": "Modeled montage coverage.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "SDE subject 5",
              "min": 3.419e-6,
              "max": 3.419e-6,
              "note": "Modeled montage coverage.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "SDE subject 6",
              "min": 2.252e-6,
              "max": 2.252e-6,
              "note": "Modeled montage coverage.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "SDE subject 7",
              "min": 4.193e-6,
              "max": 4.193e-6,
              "note": "Modeled montage coverage.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "SDE subject 8",
              "min": 2.059e-6,
              "max": 2.059e-6,
              "note": "Modeled montage coverage.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "SDE subject 9",
              "min": 1.859e-6,
              "max": 1.859e-6,
              "note": "Modeled montage coverage.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "SDE subject 10",
              "min": 2.963e-6,
              "max": 2.963e-6,
              "note": "Modeled montage coverage.",
              "endpoint": "sensing_envelope"
            }
          ]
        },
        "node": "01a150f4-0e4c-7ea1-90d9-f74ebc97e09d",
        "sources": [
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            "node": "01a0c5b6-3dcb-7df1-ae0b-3f0b21f7fb5b",
            "kind": "doi",
            "id": "10.3389/fneur.2021.669406",
            "url": "https://doi.org/10.3389/fneur.2021.669406"
          }
        ]
      },
      "field_of_view_neurons": {
        "state": "incomplete"
      },
      "measurand": {
        "state": "known",
        "value": {
          "measurands": [
            "cortical local field potential",
            "high-gamma band power",
            "action potentials (specialized micro-ECoG only)"
          ],
          "note": "Standard ECoG records surface local field potentials averaged over an estimated 10^5 neurons, with mapping/BCI use chiefly of high-gamma (~70-175 Hz) amplitude; specialized 30-micron-pitch arrays can additionally record spikes."
        },
        "node": "01a0ab72-f68a-7012-add2-dbf01a41b089",
        "sources": [
          {
            "node": "01a0548f-a559-7c93-81d3-f54ce429ac75",
            "kind": "doi",
            "id": "10.1007/s00415-024-12604-w",
            "url": "https://doi.org/10.1007/s00415-024-12604-w"
          },
          {
            "node": "01a0548f-a9d7-7951-9170-db3390bd796a",
            "kind": "doi",
            "id": "10.1038/nature11911",
            "url": "https://doi.org/10.1038/nature11911"
          },
          {
            "node": "01a0548f-b1f4-7b03-96bb-50e48fa36f90",
            "kind": "doi",
            "id": "10.1038/s41586-023-06443-4",
            "url": "https://doi.org/10.1038/s41586-023-06443-4"
          },
          {
            "node": "01a0548f-bb3f-72e3-9381-d4f2f8cefe28",
            "kind": "doi",
            "id": "10.1056/NEJMoa2027540",
            "url": "https://doi.org/10.1056/NEJMoa2027540"
          },
          {
            "node": "01a0548f-bf3f-7700-ae24-d3c252754175",
            "kind": "doi",
            "id": "10.3389/fneng.2010.00009",
            "url": "https://doi.org/10.3389/fneng.2010.00009"
          },
          {
            "node": "01a054ac-ee51-7d02-8b42-5d19746edceb",
            "kind": "doi",
            "id": "10.1016/j.neuron.2015.03.037",
            "url": "https://doi.org/10.1016/j.neuron.2015.03.037"
          }
        ]
      },
      "stimulation": {
        "state": "incomplete"
      },
      "destructiveness": {
        "state": "known",
        "value": {
          "kind": "minimally_destructive",
          "note": "Grids sit on the cortical surface without crossing the pia but need a craniotomy. In refractory-epilepsy patients with extraoperative grid monitoring, pooled rates were: neurological infection 2.3%, superficial infection 3.0%, hemorrhage 4.0%, raised ICP 2.4%. Up to 3.5% needed further surgery. Selective reporting may make these conservative."
        },
        "node": "01a14c9f-a474-7b50-82fc-03ab1495360c",
        "sources": [
          {
            "node": "01a0548f-a559-7c93-81d3-f54ce429ac75",
            "kind": "doi",
            "id": "10.1007/s00415-024-12604-w",
            "url": "https://doi.org/10.1007/s00415-024-12604-w"
          },
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            "kind": "doi",
            "id": "10.1038/s41586-023-06443-4",
            "url": "https://doi.org/10.1038/s41586-023-06443-4"
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            "node": "01a0548f-b6fa-7240-9b54-db4fb4d6e978",
            "kind": "doi",
            "id": "10.1056/NEJMoa1608085",
            "url": "https://doi.org/10.1056/NEJMoa1608085"
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            "kind": "doi",
            "id": "10.1056/NEJMoa2027540",
            "url": "https://doi.org/10.1056/NEJMoa2027540"
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          {
            "node": "01a14c9e-3c32-73a0-b894-4dc360425726",
            "kind": "doi",
            "id": "10.1111/epi.12073",
            "url": "https://doi.org/10.1111/epi.12073"
          }
        ]
      },
      "preparation": {
        "state": "known",
        "value": {
          "steps": [
            {
              "kind": "surgery",
              "note": "Craniotomy (or burr holes for chronic strips) to place subdural grid/strip electrodes on the cortical surface, with tunneled leads to a skull-fixed connector or subcutaneous transmitter; typically followed by 7-10 days of inpatient monitoring before surgical removal in clinical epilepsy workups."
            }
          ],
          "note": "Requires surgical electrode placement after craniotomy; clinical use additionally requires informed consent and inpatient monitoring until the clinical endpoint (e.g. seizures captured) is reached."
        },
        "node": "01a0ab73-1f8d-7680-b79a-eab0db0e248f",
        "sources": [
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            "node": "01a0548f-a559-7c93-81d3-f54ce429ac75",
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            "url": "https://doi.org/10.1007/s00415-024-12604-w"
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          {
            "node": "01a0548f-a9d7-7951-9170-db3390bd796a",
            "kind": "doi",
            "id": "10.1038/nature11911",
            "url": "https://doi.org/10.1038/nature11911"
          },
          {
            "node": "01a0548f-b1f4-7b03-96bb-50e48fa36f90",
            "kind": "doi",
            "id": "10.1038/s41586-023-06443-4",
            "url": "https://doi.org/10.1038/s41586-023-06443-4"
          },
          {
            "node": "01a0548f-b6fa-7240-9b54-db4fb4d6e978",
            "kind": "doi",
            "id": "10.1056/NEJMoa1608085",
            "url": "https://doi.org/10.1056/NEJMoa1608085"
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          {
            "node": "01a0548f-bb3f-72e3-9381-d4f2f8cefe28",
            "kind": "doi",
            "id": "10.1056/NEJMoa2027540",
            "url": "https://doi.org/10.1056/NEJMoa2027540"
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          {
            "node": "01a054ac-ee51-7d02-8b42-5d19746edceb",
            "kind": "doi",
            "id": "10.1016/j.neuron.2015.03.037",
            "url": "https://doi.org/10.1016/j.neuron.2015.03.037"
          }
        ]
      },
      "cost": {
        "state": "known",
        "items": [
          {
            "value": {
              "kind": "procedure",
              "currency": "USD",
              "amount_min": 104442.0,
              "year": 2020,
              "label": "Subdural-grid implant + perioperative monitoring charges (Sept 2020 USD)"
            },
            "node": "01a06f31-96a4-7881-9e79-cef46a18dfe5",
            "sources": [
              {
                "node": "01a0547d-c12b-7073-9a78-8bb37946fc9f",
                "kind": "doi",
                "id": "10.3171/2022.1.peds21523",
                "url": "https://doi.org/10.3171/2022.1.peds21523"
              }
            ]
          },
          {
            "value": {
              "kind": "procedure",
              "currency": "USD",
              "amount_min": 1512.66,
              "year": 2026,
              "label": "CPT 61533 electrode implant physician fee (45.06 RVU x $33.57 CF)"
            },
            "node": "01a06f31-9da7-76f0-b098-01d398bc51e3",
            "sources": [
              {
                "node": "01a0590c-4778-7910-af19-5ba8fecce5da",
                "kind": "url",
                "id": "https://www.cms.gov/files/zip/rvu26d-updated-08-26-2026.zip",
                "url": "https://www.cms.gov/files/zip/rvu26d-updated-08-26-2026.zip"
              },
              {
                "node": "01a0590c-53da-7332-b711-3cf640f7b8fd",
                "kind": "url",
                "id": "https://www.cms.gov/newsroom/fact-sheets/calendar-year-cy-2026-medicare-physician-fee-schedule-final-rule-cms-1832-f",
                "url": "https://www.cms.gov/newsroom/fact-sheets/calendar-year-cy-2026-medicare-physician-fee-schedule-final-rule-cms-1832-f"
              }
            ]
          }
        ]
      },
      "theoretical": {
        "description": {
          "state": "known",
          "value": {
            "text": "A spatial-resolution proxy for intracranial field-potential recording uses the cortical spread of the local field potential (LFP). Using twice the standard deviation of the spatial spread as an analytical resolution proxy, microelectrode LFP in primary visual cortex, with a cortical spread SD below about 0.5 mm, gives a proxy below about 1 mm. This is an upper bound, not a measured discrimination limit, and in auditory cortex LFP spread is much larger, up to several millimetres. A macro contact's spread is proposed to be about the LFP spread plus the electrode radius, a relationship that still awaits verification with electrodes of varying size; a 2.3 mm ECoG electrode has a spread SD of about 1.5 mm (2 SD about 3 mm).\n\nTemporally, the strongest extracellular fields generated by a single neuron last under 2 ms, and nearby neurons rarely fire synchronously within such a window under physiological conditions.\n\nCoverage has only an idealized envelope: surface contacts tiling the exposed pial surface of both hemispheres (twice one measured hemisphere's 42,619 mm²) and sensing to the 2.5 mm radius of a subdural-contact recording model would span about 2.13 × 10⁻⁴ m³. Cortex folded inside sulci lies outside this envelope, and it is not a demonstrated implant."
          },
          "node": "01a16a3d-12cb-7d91-a63c-1fc2dbd8a625",
          "sources": [
            {
              "node": "01a05488-46dd-70d2-9e15-275cb4878cd9",
              "kind": "doi",
              "id": "10.1038/nrn3241",
              "url": "https://doi.org/10.1038/nrn3241"
            },
            {
              "node": "01a0abbb-ce8a-7851-bac8-587444e8d878",
              "kind": "doi",
              "id": "10.1523/jneurosci.2917-18.2019",
              "url": "https://doi.org/10.1523/jneurosci.2917-18.2019"
            },
            {
              "node": "01a0c15a-64c1-74c2-b59e-5cb7fc87eeab",
              "kind": "doi",
              "id": "10.3389/fnana.2013.00028",
              "url": "https://doi.org/10.3389/fnana.2013.00028"
            },
            {
              "node": "01a0c5b6-3dcb-7df1-ae0b-3f0b21f7fb5b",
              "kind": "doi",
              "id": "10.3389/fneur.2021.669406",
              "url": "https://doi.org/10.3389/fneur.2021.669406"
            }
          ]
        },
        "spatial_resolution_m": {
          "state": "known",
          "value": {
            "max": 0.001,
            "unit": "m",
            "note": "Under an explicit 2-SD spatial-spread criterion for distinguishing two sources, the resolution proxy is twice the standard deviation of the recording spatial spread. This is a model assumption, not a measured discrimination limit. In-principle case: microelectrode LFP in primary visual cortex (V1). Its cortical spread, estimated as a spatial weighting function that depends mainly on electrode size, impedance and location and on tissue filtering, and confirmed by other methods, has SD < ~0.5 mm, so 2 SD < ~1 mm. With analogous methods in auditory cortex, LFP spread is much larger than MUA, extending up to several millimeters. Proposed from the ECoG comparison: a macro contact's spread ≈ LFP spread (~0.5 mm) + electrode radius (~1.15 mm), increasing linearly with electrode size. The linear macro-contact model was proposed subject to experimental verification with electrodes of varying size. Context: ECoG spread SD ~1.5 mm (2 SD ~3 mm) for a 2.3 mm diameter electrode, ~3× the LFP spread.",
            "endpoint": "two_source_separation",
            "operating_points": [
              {
                "label": "V1 microelectrode LFP spread-based proxy",
                "max": 0.001,
                "note": "2 × SD, from SD < ~0.5 mm of V1 LFP cortical spread. Upper bound only.",
                "endpoint": "two_source_separation"
              }
            ]
          },
          "node": "01a16a3b-655a-7173-a5f4-7fdd84742d99",
          "sources": [
            {
              "node": "01a0abbb-ce8a-7851-bac8-587444e8d878",
              "kind": "doi",
              "id": "10.1523/jneurosci.2917-18.2019",
              "url": "https://doi.org/10.1523/jneurosci.2917-18.2019"
            }
          ]
        },
        "temporal_resolution_s": {
          "state": "incomplete"
        },
        "field_of_view_m3": {
          "state": "known",
          "value": {
            "min": 0.000213095,
            "max": 0.000213095,
            "unit": "m3",
            "note": "Idealized area × depth envelope, not a demonstrated implant: surface contacts tiling the exposed (non-sulcal) pial surface of both hemispheres, each sensing the 2.5 mm radius used in an intracranial recording-volume model for subdural contacts. One measured human hemisphere has an exposed pial surface of 42,619 mm²; stipulating the same for the other hemisphere gives 85,238 mm². Multiplying by the 2.5 mm depth gives 213,095 mm³ (2.13095 × 10⁻⁴ m³). Stipulations: the radius transfers from the per-contact half-sphere model to a continuous slab, and cortex folded inside sulci (total grey-matter pial surface 94,050 mm² per hemisphere) lies outside the envelope.",
            "endpoint": "reachable_envelope"
          },
          "node": "01a15cde-d2b1-7761-933f-f2c1cd0addea",
          "sources": [
            {
              "node": "01a0c15a-64c1-74c2-b59e-5cb7fc87eeab",
              "kind": "doi",
              "id": "10.3389/fnana.2013.00028",
              "url": "https://doi.org/10.3389/fnana.2013.00028"
            },
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              "kind": "doi",
              "id": "10.3389/fneur.2021.669406",
              "url": "https://doi.org/10.3389/fneur.2021.669406"
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        "field_of_view_neurons": {
          "state": "incomplete"
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    },
    {
      "slug": "ect",
      "name": "ECT",
      "group": {
        "id": "stim-noninvasive",
        "name": "Non-invasive write"
      },
      "mode": "write",
      "core": true,
      "summary": {
        "value": "Electroconvulsive therapy (ECT) passes an electrical charge through the brain under brief general anaesthesia, with a muscle relaxant and oxygen. The charge is a train of brief electrical pulses applied through electrodes across both temples, on the right side only, or across the forehead, which drives a generalised seizure lasting about 30 seconds. The seizure is what is monitored: its length on the EEG and the length of the muscular seizure, timed by a cuff method. A course is usually 8 to 12 sessions, two to three times a week.",
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            "id": "10.1136/bmjopen-2022-068313",
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      "description": {
        "state": "known",
        "value": {
          "text": "Electroconvulsive therapy (ECT) is a brain-stimulation treatment that passes an electrical charge through the brain to induce a generalised seizure lasting about 30 s. The charge is delivered transcranially as a train of electrical pulses. Brief-pulse ECT uses pulses of 0.5 to 2.0 ms; ultrabrief-pulse ECT uses pulses of 0.25 to 0.3 ms. The electrodes are placed bitemporally, over the right hemisphere only (right unilateral), or bifrontally. The electrode placement and the charge relative to the seizure threshold affect both efficacy and cognitive side effects. The procedure is carried out under controlled conditions with brief general anaesthesia, a muscle relaxant and continuous oxygenation. What is monitored is the induced seizure: its duration on the EEG, and the duration of the motor seizure measured by the cuff method. Usually 8 to 12 treatments are given in a course, two or three times per week."
        },
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            "url": "https://doi.org/10.1136/bmjopen-2022-068313"
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            "id": "21494444",
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        "state": "known",
        "value": {
          "min": 0.14,
          "max": 0.14,
          "unit": "m",
          "note": "Conventional bilateral ECT at 800 mA: the modeled half-value and suprathreshold volumes encompass the whole 7 cm-radius brain sphere, giving a 14 cm equivalent-sphere diameter. The RUL/BF 800 mA configuration stimulates 94% of the brain above threshold. Smaller-electrode, lower-current configurations have different focality; the conventional-current figures here do not describe those designs. Equivalent-sphere diameter is 2r × f^(1/3).",
          "endpoint": "focal_extent",
          "operating_points": [
            {
              "label": "Bilateral ECT, 800 mA (half-value and suprathreshold volume = whole brain)",
              "min": 0.14,
              "max": 0.14,
              "note": "f = 1; 2 x 0.07 m x 1 = 0.14 m.",
              "endpoint": "focal_extent"
            },
            {
              "label": "RUL/BF ECT, 800 mA (suprathreshold volume, 94% of brain)",
              "min": 0.1371,
              "max": 0.1371,
              "note": "f = 0.94; 0.94^(1/3) ≈ 0.9796; 2 x 0.07 m x 0.9796 ≈ 0.1371 m.",
              "endpoint": "suprathreshold_extent"
            }
          ]
        },
        "node": "01a165de-f90e-7010-ac68-238b1216d628",
        "sources": [
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      "temporal_resolution_s": {
        "state": "known",
        "value": {
          "min": 0.0035714285714285713,
          "max": 0.0035714285714285713,
          "unit": "s",
          "note": "Mean individual-pulse interval about 3.57 ms at the 140 pulse-pairs/s setting: 2240 pulses in an 8 s train in the manufacturer LOW 0.25 table. This is pulse-delivery spacing, not seizure duration or independent seizure spacing.",
          "endpoint": "inter_pulse_interval",
          "operating_points": [
            {
              "label": "LOW 0.25 pulse width",
              "min": 0.00025,
              "max": 0.00025,
              "endpoint": "pulse_width"
            },
            {
              "label": "LOW 0.25 train at 100%",
              "min": 8.0,
              "max": 8.0,
              "endpoint": "session_duration"
            },
            {
              "label": "Typical induced seizure",
              "min": 30.0,
              "max": 30.0,
              "note": "Approximate background figure.",
              "endpoint": "effect_duration"
            }
          ]
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        "node": "01a15f29-6b18-7992-be8c-c9a7c227b070",
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            "kind": "doi",
            "id": "10.1097/yct.0b013e3181e48165",
            "url": "https://doi.org/10.1097/yct.0b013e3181e48165"
          },
          {
            "node": "01a15f06-da9a-7832-baa0-48fdac9259f0",
            "kind": "url",
            "id": "https://www.thymatron.com/downloads/System_IV_Instruction_Manual_Rev_21.pdf",
            "url": "https://www.thymatron.com/downloads/System_IV_Instruction_Manual_Rev_21.pdf"
          }
        ]
      },
      "field_of_view_m3": {
        "state": "known",
        "value": {
          "min": 0.00123358,
          "max": 0.00123358,
          "unit": "m3",
          "note": "Whole-brain reference for the BL placement only, under an explicit model-to-population extrapolation: apply the spherical-head model’s 100% suprathreshold fraction at 800 mA to the larger adult mean total brain volume, 0.00123358 m³. This is a conditional reference-scaled modeled volume, not a measured patient volume or proof that a reference-sized adult brain is stimulated throughout. In the same model at 800 mA, RUL/BF placements have a distinct 94% suprathreshold fraction.",
          "endpoint": "suprathreshold_volume"
        },
        "node": "01a16a27-9cfd-7502-905d-c8ab051742b4",
        "sources": [
          {
            "node": "01a0abb5-4bd2-7671-9359-eff3e4e0e3b3",
            "kind": "doi",
            "id": "10.1093/cercor/bhy109",
            "url": "https://doi.org/10.1093/cercor/bhy109"
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            "node": "01a0e55e-d34a-7332-9c19-764ef0cc1770",
            "kind": "url",
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      "field_of_view_neurons": {
        "state": "incomplete"
      },
      "measurand": {
        "state": "known",
        "value": {
          "measurands": [
            "EEG seizure duration",
            "motor seizure duration by the cuff method"
          ],
          "note": "An adequate EEG seizure was ≥25 seconds. An adequate motor seizure was ≥15 seconds. Despite adequate EEG seizures, motor seizures were inadequate in 12 of 158 patients (8%); 10 had no convulsive response."
        },
        "node": "01a0e565-70b7-7093-84d0-5dc404e7dc77",
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            "node": "01a0e564-b107-73e0-8a40-4fa637a05059",
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            "id": "21494444",
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        ]
      },
      "stimulation": {
        "state": "known",
        "value": {
          "stimuli": [
            "electric current",
            "induced generalised seizure"
          ],
          "note": "ECT delivers a transcranial electrical pulse train to drive a generalised seizure."
        },
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        ]
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      "destructiveness": {
        "state": "known",
        "value": {
          "kind": "non_destructive",
          "note": "Standard modified ECT uses skin-contact electrodes; apart from ancillary intravenous injections, no invasive technique is used. Reported findings—no evidence of specified imaging changes in early studies, post-ECT hippocampal volume increases, physical side-effects, and greater autobiographical memory loss—do not guarantee absence of harm or constitute procedural tissue destruction."
        },
        "node": "01a0c5c8-6dfc-7f02-9e8c-ac6ec425592a",
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            "kind": "doi",
            "id": "10.1192/bjp.2025.2",
            "url": "https://doi.org/10.1192/bjp.2025.2"
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          {
            "node": "01a054da-8714-7cf1-847c-b3650a216925",
            "kind": "doi",
            "id": "10.4103/psychiatry.indianjpsychiatry_239_19",
            "url": "https://doi.org/10.4103/psychiatry.indianjpsychiatry_239_19"
          },
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            "node": "01a0676d-c4e5-7613-927a-e63b0808b7a9",
            "kind": "doi",
            "id": "10.1088/1741-2560/8/1/016007",
            "url": "https://doi.org/10.1088/1741-2560/8/1/016007"
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            "node": "01a0c5c5-e50f-7a11-ba13-4f8d26f136cd",
            "kind": "url",
            "id": "https://www.health.nsw.gov.au/mentalhealth/resources/Publications/electroconvulsive-therapy-handbook.pdf",
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        ]
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      "preparation": {
        "state": "known",
        "value": {
          "steps": [
            {
              "kind": "anesthesia",
              "note": "brief general anaesthesia before each session"
            },
            {
              "kind": "other",
              "note": "muscle relaxant and continuous oxygenation administered during the induced seizure"
            }
          ],
          "note": "Delivered under controlled conditions; no surgery or genetic engineering is described."
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      "cost": {
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        "items": [
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            "value": {
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              "amount_min": 877.34,
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              "label": "Medicare OPPS HCPCS 90870 electroconvulsive therapy"
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              "label": "Model per-ECT-treatment cost, 2013 USD (sensitivity $328-$1,000)"
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                "id": "10.1186/s12888-021-03601-8",
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      "theoretical": {
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          "value": {
            "text": "For 3 cm electrodes separated by 2.2 cm at 300 mA, a 4.5% half-value volume corresponds to a 4.98 cm sphere-equivalent diameter under a 7 cm-radius brain-sphere model. The approximately 2 cm half-value depth is a separate penetration measure. Bilateral ECT drives a suprathreshold electric field throughout the modelled brain; the 1.23358 × 10⁻³ m³ value is a conventional large-brain reference, not a measured stimulated volume. Other montages reach over 90% of modelled brain volume."
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          "value": {
            "min": 0.0498,
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            "note": "Stipulated sphere-equivalent spatial resolution: a 7 cm-radius brain sphere has volume (4/3)π(7 cm)^3 ≈ 1,437 cm³; 4.5% is ≈64.7 cm³, whose sphere-equivalent diameter is 2×7 cm×0.045^(1/3) = 4.98 cm = 0.0498 m. This applies to 3 cm-diameter electrodes spaced 2.2 cm apart at 300 mA. Its approximately 2 cm half-value depth is a penetration measure retained only for comparison.",
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        "field_of_view_m3": {
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            "min": 0.00123358,
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            "note": "Whole brain: bilateral-electrode ECT drives a suprathreshold electric field in 100% of the modeled brain volume. The value is the larger adult mean total brain volume (male, 1233.58 cm3), used as a conventional reference size for a large brain, not a measured stimulated volume. Other ECT montages reach over 90% of brain volume.",
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        "value": "Conventional wet scalp EEG is a non-invasive recording of the brain's electrical activity through gel-coupled electrodes on the scalp. What it reads is the electric potential at the scalp, which arises from currents crossing nerve cell membranes, mainly synchronized currents at the synapses of aligned cortical cells. That potential is a smoothed electrical trace of the neural currents themselves, blurred over several square centimetres of cortex by the skull and tissue in between. Timing is in principle milliseconds, but the spread of current through the head can distort it.",
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          "text": "Conventional wet scalp electroencephalography (EEG) is a non-invasive recording of the brain's oscillating electric potentials from electrodes on the scalp, with conductive gel between skin and electrode to carry the charge. The recorded quantity is the extracellular electric potential at the scalp: a local field potential smoothed in space and time. It arises from transmembrane currents, mainly synaptic and postsynaptic activity, with contributions from calcium spikes, other intrinsic events, action potentials and afterpotentials. Its generators are attributed to synchronous postsynaptic currents in aligned pyramidal cells. In space the scalp signal is a volume-conducted, blurred superposition of synchronous cortical activity over extended cortical patches. Tissue, especially the skull, attenuates it, and the attenuation depends on the source extent: with at least 10 cm² of active cortex, the predicted cortical-to-scalp potential ratio is about 2 to 6 because many source contributions superpose. Low-density montages resolve roughly 5 to 9 cm; simulations with 64 or more electrodes achieve about 1–3 cm, depending on electrode density; dense sampling alone is insufficient, and source modelling or surface-Laplacian (current source density) processing can improve the resolution. In time the resolution is in principle milliseconds, but volume conduction and reference effects can distort scalp-potential time courses and misestimate latencies; surface-Laplacian processing can substantially improve the recovered timing."
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          "note": "Conventional low-density scalp EEG resolves roughly 5-9 cm, typically no better than about 5 cm; surface-Laplacian/CSD and cortical-imaging processing bring this to about 2-3 cm, and simulations with 64 or more electrodes reach about 1-3 cm, matching order-of-magnitude summaries of about 1 cm.",
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              "note": "Roughly 5-9 cm, typically no better than about 5 cm and sometimes worse, owing to spatial blurring and reference effects."
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              "note": "Simulations with 64 or more electrodes achieved about 1-3 cm depending on electrode density."
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          "note": "Reciprocal-bandwidth timing approximation dt ~ 1/B, explicitly assuming that the highest neural frequency B detected above noise represents the effective temporal bandwidth. This is a model-based timing proxy, not a measured minimum separation between two events. During electrical stimulation of the median nerve, scalp recordings show a 600 Hz burst with submicrovolt amplitude and an extremely weak 1 kHz component, extracted from noise only by massive averaging, giving dt of about 1/600 to 1/1000 s (1.7 to 1 ms). Above 500 Hz, signal amplitudes commonly fall below the intrinsic noise floor of standard EEG/MEG systems, which precludes single-trial analysis of those frequencies, so these figures describe averaged evoked responses.",
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            "text": "Scalp EEG spatial pattern resolution is about 1–3 cm. This comes from simulations of isolated or distributed cortical-source patterns using surface-Laplacian and cortical-imaging reconstruction with at least 64 electrodes. It is a pattern-discrimination result that depends on electrode density, not a universal physical minimum or a single-dipole localization error. The anatomical coverage envelope is whole brain. This is a theoretical envelope, not a measured sensitivity volume. In a four-layer head model, potential falls through the skull to about 1/500 of its inner-CSF value, while scalp attenuation is small. The model sets skull resistivity at 80× brain and CSF at 1/5 brain, though the qualitative result does not depend critically on these values. When 10 cm² or more of cortex is active, superposition reduces the cortical-to-scalp potential ratio to about 2–6. Laplacian methods estimate local current density entering the scalp and can estimate cortical surface potential. They favour local, mainly cortical, sources; source nature or location is a separate, physiology-informed step. Temporally, under the approximation dt ~ 1/B, with B the highest-frequency neural content above noise at the scalp, dt is about 1–1.7 ms (B ~600–1000 Hz). This applies to median-nerve responses with very-low-noise amplifiers and massive averaging. It is limited by submicrovolt signal amplitude against amplifier and thermal noise."
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            "note": "Reciprocal-frequency timing approximation dt ~ 1/B, assuming the highest physiological frequency detected above noise defines the effective temporal bandwidth; this is a model proxy, not measured two-event discrimination. The limit is neural signal amplitude against noise. Above 500 Hz, signals commonly fall below the noise floor of standard MEG systems, whose magnetic white noise is about 10× that of ultralow-noise SQUID MEG. Remaining noise sources are amplifier noise (a ceiling of ≤4 nV/√Hz is recommended for EEG), sensor noise, and body thermal noise. The ultralow-noise SQUID MEG white noise (0.18 fT/√Hz) is close to the estimated thermal magnetic noise of a living human body, and the residual offset at the highest frequencies is attributed mainly to body thermal noise. Ultralow-noise SQUID MEG resolved the median-nerve-evoked ~600 Hz population-spike bursts in single trials. Averaging over 2,000 trials was used to demonstrate the evoked burst (about 20 ms latency). The scalp EEG 600 Hz burst and 1 kHz component with very-low-noise amplifiers were extracted from noise only by massive averaging.",
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            "min": 0.00123358,
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            "note": "Whole-brain anatomical coverage; sensitivity is not uniform throughout the brain.",
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            "id": "https://www.emotiv.com/products/insight",
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      "summary": {
        "value": "Dry-electrode EEG is scalp EEG recorded through electrodes that use no conductive gel or paste. It reads the electrical activity of the cerebral cortex at the scalp. Without gel the electrode-skin impedance is much higher, 150 to 200 kΩ against 5 to 10 kΩ with gel, and a dry cap has lower and more spatially variable channel reliability than a gel cap. Resting-state EEG and the P300 response are captured adequately; activity below 6 Hz and gamma at 40 to 80 Hz are harder to record.",
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          "text": "Dry-electrode scalp EEG is a recording of the electrical activity of the cerebral cortex, through scalp electrodes that use no conductive gel or paste. In conventional wet EEG preparation, each site is rubbed with abrasive paste to remove part of the stratum corneum, the outer skin layer that dominates skin impedance, and the popular Ag/AgCl electrodes are impregnated with an electrolyte gel that passes the ionic currents from the tissue into electric currents in the electrode; the electrode-skin impedance is then checked and typically reaches 5 to 10 kΩ. A dry electrode omits the gel and the paste, so its impedance is much larger: typically 150 to 200 kΩ. Needle-type dry electrodes pierce the stratum corneum with microneedles to reach the lower-impedance layers beneath; they are minimally invasive, and an electrode of 8 by 8 pyramidal microneedles in 10 mm² reached 13 kΩ, but such tips can split, cause infection and mismatch the impedance between electrodes. Wet contact also drifts: the impedance of gel electrodes rose from 5 to 15 kΩ within 5 hours of application. A dry cap compared with a gel cap had a mean channel reliability of 84 ± 11% against 97 ± 3%, reduced mainly at central, parietal and neck sites. In dry-electrode recordings, resting-state EEG and the P300 evoked response were adequately captured, whereas low-frequency activity below 6 Hz and induced gamma activity at 40 to 80 Hz presented notable challenges."
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          "note": "Estimated transfer from scalp-EEG figures, not a dry-EEG spatial-resolution measurement. A multi-parameter study of dry and gel-based EEG caps reports evidence for their equivalence under multiple aspects of signal characteristics in the time, frequency and spatial domain, under laboratory conditions without movements, with differences below 5% in all comparison metrics applied to the 84% good channels. Transferring the scalp-EEG figures on that basis, the finest is about 1-3 cm, from simulations with 64 or more electrodes.",
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              "note": "Estimated 1-3 cm, depending on electrode density."
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            "id": "10.2147/NDT.S177804",
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            "id": "10.1016/j.neuron.2015.03.037",
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          "note": "About 16.7 ms as a bandwidth-derived timing scale dt ≈ 1/B, using the approximately 60 Hz visually induced gamma signal detected significantly with all three dry-electrode devices in the benchmark. Gamma changes were smaller and briefer than with standard gel EEG; only the gel system captured a sustained robust response. This is a bandwidth-derived scale for that visual response, not directly measured two-event separation or guaranteed single-trial timing.",
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              "note": "About 50 ms as a bandwidth-derived scale dt ≈ 1/B with B = 20 Hz demonstrated in the dry-electrode SSVEP analysis. Averaged waveforms contained clear 20 Hz spectral content, and the 20 Hz stimulus response had mean SNR 10.29 dB across subjects. This is a bandwidth-based timing scale for the evoked regime, not directly measured two-event separation or a universal fastest dry-EEG limit.",
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          "note": "Anatomical whole-brain reference: 1.23358 × 10⁻³ m³, the adult male mean total brain volume from a UK Biobank cohort of 5,216 adults. It is used as a stipulated size reference, not a measured sensing envelope. The dry-cap study establishes a 256-channel layout matching the gel-based reference cap and records activity over scalp regions; those observations do not quantify the sensitive tissue volume."
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          "note": "Dry electrodes record cortical electrical activity non-invasively at the scalp. In a cap comparison, mean channel reliability was 84 ± 11% for the dry cap and 97 ± 3% for the gel cap; the tested dry cap had higher impedance and more spatially variable reliability. Comparison evidence supports capture of resting EEG and P300, with challenges below 6 Hz and at 40–80 Hz."
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        "state": "incomplete"
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        "state": "known",
        "value": {
          "kind": "non_destructive",
          "note": "Dry multipin EEG records from electrodes resting on the scalp, outside the brain. Pins of 6 mm (dense hair) and 3 mm (less dense hair) and 'wave pins' (a flat surface with 19 half-spheres of 1.5 mm diameter, for the forehead) give electrode-skin contact. Mean comfort ratings were in the lower half of 1–10, i.e. 'not painful', for both dry and gel electrodes."
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          "steps": [
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              "kind": "other",
              "note": "Clean both mastoids with ethanol."
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          "note": "Beyond sensor placement, both mastoids are cleaned with ethanol; no other sites are cleaned. The dry cap uses no skin abrasion or scalp gel/paste application, although pre-gelled hydrogel ECG electrodes provide mastoid ground/reference. Preparation averaged 19 ± 4 min versus 62 ± 9 min for the gel cap."
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            "text": "Spatially, dry scalp EEG is estimated in principle to discriminate cortical-source patterns roughly 1–3 cm apart. This is not a universal minimum or single-dipole localization error. The figure is an estimated transfer, not a directly measured or simulated dry-EEG figure. It comes from wet-EEG surface-Laplacian/cortical-imaging simulations with at least 64 spatial samples and is applied to a comparably dense dry montage because dry and gel caps are reported equivalent in the spatial domain. Temporally, the stipulated convention is dt ~ 1/B, where B is the highest-frequency physiological signal shown above noise at the scalp. B was obtained with median-nerve stimulation, very-low-noise amplifiers and massive averaging with signal processing. Under those conditions it covers a submicrovolt ~600 Hz burst and an extremely weak ~1 kHz component, so B ~600–1000 Hz and dt ~1–1.7 ms. That bound is set by neural signal amplitude against amplifier, sensor and body thermal noise. Above 500 Hz, amplitudes commonly fall below standard EEG noise floors. No dry montage is shown to reach this bound."
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            "note": "Estimated in-principle transfer to a comparably dense dry montage, based on reported dry-versus-gel cap equivalence in the spatial domain; not directly measured or simulated for dry EEG. The 1–3 cm range concerns simulated discrimination of cortical-source patterns with surface-Laplacian/cortical imaging and at least 64 spatial samples, not a universal minimum or single-dipole localization error."
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            "note": "Reciprocal-frequency timing approximation dt ~ 1/B, assuming the highest physiological frequency detected above noise defines the effective temporal bandwidth; this is a model proxy, not measured two-event discrimination. The limit is neural signal amplitude against noise. Above 500 Hz, signals commonly fall below the noise floor of standard MEG systems, whose magnetic white noise is about 10× that of ultralow-noise SQUID MEG. Remaining noise sources are amplifier noise (a ceiling of ≤4 nV/√Hz is recommended for EEG), sensor noise, and body thermal noise. The ultralow-noise SQUID MEG white noise (0.18 fT/√Hz) is close to the estimated thermal magnetic noise of a living human body, and the residual offset at the highest frequencies is attributed mainly to body thermal noise. Ultralow-noise SQUID MEG resolved the median-nerve-evoked ~600 Hz population-spike bursts in single trials. Averaging over 2,000 trials was used to demonstrate the evoked burst (about 20 ms latency). The scalp EEG 600 Hz burst and 1 kHz component with very-low-noise amplifiers were extracted from noise only by massive averaging.",
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            "note": "Whole-brain anatomical coverage; sensitivity is not uniform throughout the brain.",
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        "value": {
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          "unit": "m",
          "note": "Rat somatosensory cortical EIT with an invasive 30-electrode epicortical array reports resolution below 200 micrometers. The matching reconstruction methodology has a modeled positional-accuracy bound below 200 micrometers in a 5 × 4 × 1.4 mm volume under the array; this is not a scalp-EIT resolution or a two-source separation.",
          "endpoint": "localisation_error"
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        "node": "01a165f0-b3fd-7dc0-99e7-58dcdb5ebf5d",
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            "id": "10.1016/j.neuroimage.2015.08.071",
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        "value": {
          "min": 0.002,
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          "unit": "s",
          "note": "Reported effective temporal resolution of 2 ms derived from a ±500 Hz demodulation bandwidth around a 1.725 kHz carrier in a 57-electrode epicortical EIT protocol. This is a bandwidth-derived timing estimate, not a measured threshold for separating two independent neural events or a scalp-EIT result.",
          "endpoint": "recoverable_timing"
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            "id": "10.1016/j.nicl.2018.09.004",
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      "summary": {
        "value": "An endovascular brain-computer interface is an electrode array mounted on a stent and threaded through the jugular vein into the superior sagittal sinus, a large vein next to the motor cortex. From inside the vein it records electrocorticography, the electrical field produced by sensorimotor cortex activity, sensed through the vessel wall; this is a direct electrical measure of brain activity. The approach avoids open-brain surgery, but the implant is still an invasive vascular procedure.",
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            "id": "10.1038/nbt.3428",
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      "row_node": "01a16b6b-2b4f-7502-a87b-19219e21fa48",
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        "value": {
          "text": "An endovascular brain-computer interface is an electrode array mounted on a stent and placed inside a cerebral vein, where it records the electrical activity of the cortex from within the vessel wall. The array is delivered through the internal jugular vein into the superior sagittal sinus, a large vein adjacent to the precentral gyrus, and a lead is tunnelled under the skin to an electronics pocket. The approach is an alternative to placing electrodes in or on the dura by open-brain surgery. The implant is still an invasive vascular procedure. The signal is electrocorticography (ECoG): field potentials produced by sensorimotor cortex activity, sensed through the sinus wall, which in sheep is 200 to 600 µm thick. In sheep, electrodes 2.4 mm apart on the stent recorded distinguishable waveforms, with bandwidth and signal-to-noise ratio comparable to epidural and subdural arrays; spatial resolution there was limited by electrode spacing and size. In a ten-participant human analysis, the electrodes sat at different points around the stent's circumference, some closer to the cortex and others within the opposite wall of the sinus; a simplified model that placed the array along the middle of the sinus put it on average 6.1 ± 1.5 mm from the cortical surface."
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          "note": "In sheep, electrodes in the superior sagittal sinus recorded distinguishable cortical electrophysiological waveforms at 2.4 mm electrode spacing, with variable morphology and low interelectrode Pearson correlation (0.06 ± 0.03). This is a sampling-spacing figure. The findings suggest achievable spatial resolution at that scale, but do not establish a two-source separation limit; the experiment did not establish maximum electrode sensitivity or spatial resolution.",
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          "note": "Reciprocal-frequency timing estimate: assume the highest neural frequency detected above noise defines an effective temporal bandwidth, and take recoverable timing as dt ≈ 1/B. This is an assumed proxy, not measured two-event discrimination. Recoverable timing is taken as dt ≈ 1/B, where B is the highest recorded neural-signal frequency. For the SWITCH endovascular array, B was a mean of 233 Hz (SD 16; participant range 206–245 Hz), defined as the highest frequency band with mean power above the noise floor. This gives dt ~ 4.3 ms at the mean, and about 4.1–4.9 ms across participants. This is an estimate from recorded spectral bandwidth, not a demonstrated neural temporal resolution and not a decoded-command rate. A sampling interval or Nyquist half-period (1/(2B)) is not the resolution.",
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        "value": {
          "min": 4.215e-7,
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          "unit": "m3",
          "note": "Modelled contact-centred sensing envelope of the 16-contact SWITCH endovascular array (3 mm intercontact spacing), not a measured or grey-matter volume. Stipulations, none validated: the subdural-electrode half-sphere model (2.5 mm radius per single-surface contact) applies to endovascular contacts, the contacts lie in a straight line, and all half spheres share one flat boundary plane through the contact centres and face the same side, so the envelope is half the union of full spheres. Arithmetic with r = 2.5 mm, s = 3 mm, N = 16: sphere = (4/3)π(15.625) = 65.45 mm³; 16 × 65.45 = 1047.20 mm³; lens shared by neighbours = π(13)(2)²/12 = 13.61 mm³; 15 × 13.61 = 204.20 mm³; V = ½(1047.20 − 204.20) = 421.5 mm³ ≈ 4.215×10⁻⁷ m³. Geometry caveat: in human participants a model placing the array along the middle of the superior sagittal sinus put it on average 6.1 ± 1.5 mm from the cortical surface (minimum 3.7 ± 1.2 mm), beyond the 2.5 mm radius, while individual contacts sit around the stent circumference, some closer to the cortex. In sheep the electrode was 260-680 µm from the brain. The envelope therefore need not coincide with the cortex the array senses.",
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        "node": "01a15cc8-bddd-7a33-8f21-64b14bc89039",
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            "id": "10.3389/fneur.2021.669406",
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          "measurands": [
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          "note": "The endovascular electrode array records ECoG signals resulting from sensorimotor cortex activity."
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          "kind": "minimally_destructive",
          "note": "Implantation punctures the internal jugular vein, uses incisions, tunnels a lead, creates a subcutaneous pocket, and leaves a permanent implant in the superior sagittal sinus; brain tissue is not reported penetrated or lesioned. In four participants, reported effects included incision-site bruising, headache, and hematoma near the jugular insertion site; at 12 months, no device-related serious adverse events causing death or permanent disability and no target-vessel occlusion or thrombosis were found, and eight mild effects resolved without intervention."
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        "value": {
          "min": 2.58e-8,
          "max": 2.58e-8,
          "unit": "m",
          "note": "Measured full-process PSF FWHM for iterative expansion microscopy (~20×) is 25.8 ± 7.7 nm on single microtubule sidewalls, including staining, gelation, expansion and optical imaging. The mean is 25.8 nm; ±7.7 nm is the reported uncertainty. Original ~4.5× expansion with confocal imaging has estimated effective resolution ~70 nm lateral and ~200 nm axial, from diffraction limit divided by expansion. Protocol and axis matter; the iterative result is not an axial measurement.",
          "endpoint": "point_spread",
          "operating_points": [
            {
              "label": "Original ExM (~4.5x, confocal), lateral",
              "min": 7e-8,
              "max": 7e-8,
              "note": "About 70 nm, estimated by dividing the confocal diffraction limit by ~4.5x expansion.",
              "endpoint": "point_spread"
            },
            {
              "label": "Original ExM (~4.5x, confocal), axial",
              "min": 2e-7,
              "max": 2e-7,
              "note": "About 200 nm, estimated by dividing the confocal diffraction limit by ~4.5x expansion.",
              "endpoint": "point_spread"
            },
            {
              "label": "Iterative ExM (~20x), rounded 25.8 nm measurement",
              "min": 2.5e-8,
              "max": 2.5e-8,
              "note": "~25 nm resolution on conventional microscopes. Measured full-process PSF FWHM on single microtubule sidewalls is 25.8 ± 7.7 nm, covering staining, gelation, expansion and optical imaging. The ± is the stated uncertainty. Applied to imaging synaptic proteins and dendritic spines in mouse brain. No axial figure is given.",
              "endpoint": "point_spread"
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        "state": "unknown",
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          "reason": "These protocols image fluorescent labels retained in fixed, gel-anchored, expanded tissue to infer static structure (morphology, synaptic marker pairs). Each sample is a single fixed-state spatial snapshot with no ongoing neural time series, so a neural temporal sampling resolution does not apply; scan duration is acquisition time only."
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        "value": {
          "min": 4e-7,
          "max": 4e-7,
          "unit": "m3",
          "note": "Entire mouse brains were cleared, expanded (3×) and imaged on a light-sheet microscope without sectioning. The specimen volume is not stated; 4×10^-7 m^3 is a proxy, stipulating the ~400 mm^3 given for a whole mouse brain in a separate whole-brain imaging study. At this scale the effective resolution is 375 nm lateral and 750 nm axial at 4× expansion (about 0.5 µm and 1 µm at 3×), far coarser than the nanoscale figures of the small-volume protocols in the operating points. Iterative expansion microscopy at about 20× has a separate small-volume full-process PSF measurement of 25.8 ± 7.7 nm; that resolution is not the whole-brain light-sheet result.",
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            {
              "label": "PRISM, mouse hippocampal CA3, pre-expansion",
              "min": 1e-11,
              "max": 1e-11,
              "note": "About 10 million µm^3 of native tissue.",
              "endpoint": "acquired_volume"
            },
            {
              "label": "Original ExM, adult Thy1-YFP-H mouse hippocampus, ~4.5× expansion",
              "min": 9e-12,
              "max": 9e-12,
              "note": "500×180×100 µm = 9×10^6 µm^3 → 9×10^-12 m^3. This was imaged on a spinning-disk confocal (40×, 1.15 NA), with an estimated effective resolution of ~70 nm lateral and ~200 nm axial. The separate iterative protocol at about 20× expansion has a measured 25.8 nm full-process PSF FWHM.",
              "endpoint": "acquired_volume"
            },
            {
              "label": "Light-microscopy connectomics, mouse S1 cortex L2/3–4, stitched field",
              "min": 9.5e-13,
              "max": 9.5e-13,
              "note": "396×109×22 µm ≈ 0.95×10^6 µm^3 pre-expansion → 9.5×10^-13 m^3. The volume was stitched from 132 tiles (6×22 grid, SOFIMA fusion). Effective voxel size was 9.7×9.7×25.9 nm, and imaging took 6.5 h on a spinning-disk confocal. The 3.5×10^9 µm^3 figure is the post-expansion size and is not coverage.",
              "endpoint": "acquired_volume"
            },
            {
              "label": "ExLLSM, Drosophila DC3 PN tracing volume, 4× expansion",
              "min": 5.47e-12,
              "max": 5.47e-12,
              "note": "250×175×125 µm ≈ 5.47×10^6 µm^3 → ~5.5×10^-12 m^3. The source gives dimensions in pre-expanded (biological) units.",
              "endpoint": "acquired_volume"
            },
            {
              "label": "ExLLSM, whole Drosophila brain (TH-GAL4/nc82), 4× expansion",
              "note": "The whole brain was imaged in 62.5 h at a stated 3.2×10^5 µm^3/hr. The product is approximately 2×10^7 µm^3, but the volume-rate units are ambiguous between native and expanded tissue.",
              "endpoint": "acquired_volume"
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        "state": "known",
        "value": {
          "min": 298.0,
          "max": 298.0,
          "unit": "neuron",
          "note": "PRISM identified 298 somata in one acquired mouse hippocampal CA3 volume of approximately 10 million µm³ before expansion. Of these, 146 contained at least one protein bit; 80% of those labelled somata had a unique barcode. The volume was imaged across 8 stripping cycles and 12 imaging rounds.",
          "endpoint": "acquired_volume",
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              "min": 146.0,
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              "note": "Labelled subset of the 298 somata in the same acquired volume (49%).",
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          "measurands": [
            "fluorescence of gel-anchored labels (antibodies, fluorescent proteins) in expanded tissue",
            "relative spatial distribution of labeled molecules",
            "pre- and postsynaptic protein marker localization (e.g., Homer1/PSD95, Bassoon)"
          ],
          "note": "In fixed, protease-digested, isotropically expanded mouse brain tissue (and whole Drosophila brain), confocal or light-sheet imaging records fluorescent-tag positions retained in the gel. Structure is inferred from this: neuronal morphology and spine shape, myelination patterns, boutons, and apposed pre/postsynaptic marker pairs that indicate putative synapses, which are then counted and assigned to traced neurites. It is an indirect, label-based structural proxy of the fixed tissue state."
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          "reason": "The technique only reads out structure from tissue that is already fixed (PFA/formalin perfusion or immersion) before processing: anchoring, denaturation, expansion, immunostaining and fluorescence imaging of gel-retained labels. None of these steps writes neural activity, and fixed tissue has no ongoing activity to drive. A stimulation parameter therefore has nothing to describe; it is not a value that is merely unreported."
        },
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          "kind": "terminal",
          "note": "Expansion microscopy is performed ex vivo on fixed tissue. In mouse protocols the animal is anesthetized and perfusion fixed, the brain is harvested, and it may be cut into 50 µm cryostat sections or 50 to 250 µm vibratome slices; fly brains are dissected before fixation; human protocols use formalin-fixed post-mortem brain tissue. The specimen is then embedded in a swellable hydrogel, softened by proteolytic digestion or heat and detergent denaturation, and swollen in water about 4 to 4.5 fold in one round, or about 20 fold with re-embedding; unanchored lipids and other components are removed. The tissue under study is killed, fixed and chemically transformed into an expanded gel before confocal or light-sheet imaging, so the classification is terminal for the sampled tissue."
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          "steps": [
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              "kind": "anesthesia",
              "note": "Mouse protocols anesthetize animals before transcardial perfusion; the AAV-barcode protocol specifies terminal pentobarbital anesthesia."
            },
            {
              "kind": "surgery",
              "note": "After perfusion, mouse brains are harvested/dissected; fly brains are dissected before fixation."
            },
            {
              "kind": "other",
              "note": "Animal brains are fixed or post-fixed. ExRPath/15ExMPath instead use formalin-fixed post-mortem human brain tissue."
            },
            {
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              "note": "Mouse brains may be sectioned into 50 µm cryostat sections or 50–250 µm vibratome slices, depending on the protocol."
            },
            {
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              "note": "Protocol-specific options include Thy1-YFP transgenic mice and split-GAL4 fly lines; these are not universal ExM requirements."
            },
            {
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              "note": "The protein-barcode protocol specifically requires surgical AAV injection with analgesia at least three weeks before terminal perfusion; this is not universal."
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            },
            {
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              "note": "Specimens are embedded in swellable hydrogel. Human pathology protocols first use AcX to anchor proteins; the original method uses gel-anchorable labels."
            },
            {
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              "note": "Tissue is chemically softened after polymerization by proteolysis or by heat/detergent denaturation; archival human tissue uses high-temperature, pressurized treatment."
            },
            {
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              "note": "Water swelling expands the gel about 4–4.5×; ExRPath can re-embed and swell again to approximately 20×."
            }
          ],
          "note": "Expansion microscopy is performed ex vivo on fixed tissue; preparation varies by protocol."
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      "cost": {
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          {
            "value": {
              "currency": "USD",
              "amount_min": 40.0,
              "amount_max": 180.0,
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              "label": "Overall experimental costs, as stated by the source, for a typical sample (e.g., a 50–100 µm thick full-width mouse brain slice) using RNA-binding anchoring reagents: LabelX $180; MelphaX $40 (range bounds $40–$180). Prices as of late 2022. Currency USD is inferred from the '$' symbol in a source authored at MIT's McGovern Institute (Cambridge, Massachusetts, USA). The source does not itemize what these totals include."
            },
            "node": "01a151b2-b200-7ac3-9c52-574c88b9acfc",
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            },
            "node": "01a151b3-37ac-7193-803a-9abc2ee8205b",
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            "text": "Spatially, expansion microscopy is limited by label placement as expansion grows. Combining the X10 gel with iterative expansion to reach lateral expansion factors of up to 100× would theoretically offer a resolution of up to 3 nm, useful only with probes smaller than antibodies. With conventional primary/secondary antibodies and epifluorescence, ~25 nm is possibly the maximum useful resolution, because antibodies displace fluorophores from their epitopes (~6 nm for the Pmp70 membrane protein) and enlarge the perceived objects. Measured and simulated X10 figures are 25.2 nm and 22.8 nm.\n\nTemporally, a sampling interval for neural dynamics does not apply: the tissue is fixed before anchoring and expansion, so each sample is a single fixed-state snapshot."
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          "min": 0.05,
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          "note": "Fastest demonstrated tested inter-stimulus interval associated with resolved dopamine-transient peaks using dLight1.1 fiber photometry in mouse nucleus accumbens during optogenetic stimulation of VTA dopamine neurons. Individual peaks were detected at 5, 10, and 20 Hz; plotted fluorescence responses were averaged across n=5 mice. This is not a universal minimum, digital sampling period, separability threshold, single-trial spike resolution, or result transferable to GCaMP calcium or other sensors.",
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              "note": "Fastest tested stimulation frequency at which individual dopamine-transient peaks were detected.",
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              "label": "Reported fiber-photometry system cost of $22,200; dollar denomination and purchase type unspecified"
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    {
      "slug": "five-ala",
      "name": "5-ALA fluorescence guidance",
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        "value": "Functional MRI at 7 tesla is magnetic resonance imaging of the human brain that infers neuronal activity from blood oxygenation. In gradient-echo BOLD imaging the signal falls as local deoxyhemoglobin rises; after neuronal activity increases, blood flow rises more than oxygen use, so deoxyhemoglobin drops near active sites and in downstream draining veins. What it reads is BOLD image intensity, an indirect measure of neuronal activity, and the venous contribution limits spatial specificity. At 7 T in humans, spin-echo BOLD gave narrower estimated point-spread functions than gradient-echo BOLD.",
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          "text": "Human functional MRI infers local changes in neuronal activity from task-invoked metabolic and hemodynamic responses, so its signal is an indirect measure of neuronal activity. In gradient-echo blood oxygenation level dependent (BOLD) imaging, the signal is inversely proportional to local deoxyhemoglobin content. After neuronal activity rises, local arterial cerebral blood flow increases more than oxygen consumption, which lowers deoxyhemoglobin in capillaries. This change propagates from capillaries at active sites downstream to draining veins, so large veins distant from those sites contribute functional mapping signals. That venous contribution impairs spatial specificity and adds to any intrinsic imprecision in coupling between blood flow and neuronal activity. Intermediary non-neuronal events limit specificity in space and how that specificity changes over time. A spatio-temporal point-spread function in human gray matter describes these limits. At 7 T in humans, estimated point-spread functions were narrower for spin-echo BOLD than for gradient-echo BOLD. These estimates reflect realistically achievable specificity at that field strength but are only upper bounds on the true widths. In human resting-state 7 T fMRI, functional connectivity between regional signals may reflect both monosynaptic and polysynaptic connections. Higher-resolution acquisition, minimal smoothing and nuisance regression using signals from individual ventricles can mitigate low signal-to-noise, partial volume effects and physiological aliasing."
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          "note": "Human 7 T BOLD fMRI, V1. The most probable SE BOLD PSF FWHM of 0.82 mm from ocular dominance column responses. This is an upper bound on the true BOLD PSF width, with no finite lower bound. It is not a universal limit and not an uncertainty interval bounding the intrinsic PSF. GE BOLD gave 1.02 mm by the same method, also an upper bound. In four healthy subjects, pooled approximately flat V1 gray matter, with lines overlapping macro-vessel-mask voxels excluded, gave an observed Gaussian GE BOLD PSF FWHM of 2.34 ± 0.20 mm (95% CI). The 1.1-mm and 2-mm isotropic voxels are protocol sampling only.",
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            "text": "Intrinsic hemodynamic spread limits fMRI spatial specificity. In cat visual cortex, perfusion-based CBF imaging gave an approximately 470 μm response FWHM, treated as a conservative upper-bound scale that can vary with species, region and task. Human V1 BOLD measurements at 7 T give upper bounds of 0.82 mm for spin-echo and 1.02 mm for gradient-echo PSF widths; these are field-specific operating points, not measurements at 1.5 or 3 T. Whole-brain 3 T acquisitions support the conventional large-brain reference volume of 1.23358 × 10⁻³ m³, not a measured acquisition-box volume."
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            "note": "The intrinsic hemodynamic spread limits fMRI spatial specificity. In cat visual cortex, perfusion-based (cerebral blood flow) fMRI largely free of draining-vein contamination resolved orientation columns spaced 1.1 mm apart, and the CBF response to a single stimulus had an FWHM of about 470 um, a conservative, slightly overestimated width that may differ across species, regions or tasks. Measured human BOLD point-spread widths are only upper bounds on the true widths: 0.82 mm for spin-echo and 1.02 mm for gradient-echo BOLD at 7 T in V1, the realistically achievable specificity at that field strength.",
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        "value": "fNIRS is a noninvasive optical brain-imaging method in which sensors on the scalp shine near-infrared light (650 to 950 nm) into the head and detect the light scattered back at several wavelengths. From how much light is absorbed across wavelengths and over time, it estimates changes in oxygenated and deoxygenated hemoglobin in the outer brain, an indirect, blood-flow-based sign of brain activity. Continuous-wave systems give only changes from a baseline, and blood flow in the scalp can contaminate the signal and be mistaken for brain activity.",
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          "text": "Functional near-infrared spectroscopy (fNIRS) is noninvasive optical neuroimaging. Light sources and detectors (optodes) on the scalp send near-infrared light of 650 to 950 nm into the head and record the intensity of the light scattered back at several wavelengths. Oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR) absorb these wavelengths differently, so the method uses the change in attenuation across wavelengths and over time to estimate task-linked changes in HbO2 and HbR concentration in the cortex under the optodes. The result is a hemodynamic brain signal. The hemoglobin changes are estimated from the attenuation; they are not measured directly. Continuous-wave systems, the most widely deployed kind, give only changes relative to baseline, because they cannot separate absorption from scattering. Time-domain and frequency-domain systems separate the two and recover absolute concentrations, and time-domain systems also resolve depth and path length; both kinds are less available. The recorded signal includes blood perfusion and oxygenation in extracerebral tissue, especially the scalp, as well as in the cortex, and this scalp contribution can be mistaken for brain activity."
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          "unit": "m",
          "note": "The finest modeled HD-DOT point-spread FWHM is 8.2 mm. Across target locations it ranges from 8.2 to 17.2 mm, with a mean of 12.1 ± 1.4 mm. FWHM is the maximum separation of pairs of reconstructed points above half-maximum contrast. This is a reconstruction simulation, not an in-vivo separation measurement. The 13.5 ± 2.2 mm effective-resolution metric additionally includes localization error.",
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          "max": 0.02,
          "unit": "s",
          "note": "At 50 Hz sampling, fNIRS produces one sample every 20 ms; systems sampling at up to 10 Hz have intervals of about 100 ms or longer. Hemodynamic responses peak about 5–6 s after stimulus onset and return to baseline at about 16 s, varying across regions, tasks and participants. These sample intervals do not imply neural-event resolution.",
          "endpoint": "sample_interval",
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              "endpoint": "sample_interval"
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            "id": "10.1016/j.neuroimage.2003.12.041",
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        "value": {
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          "max": 0.000112,
          "unit": "m3",
          "note": "The reconstruction used a 10-mm-thick cortical shell (radius 65–75 mm) averaged in depth into a 140 mm × 80 mm posterior coronal projection. Treating that curved shell as a flat 140 × 80 × 10 mm slab (a stipulated approximation) gives 112,000 mm³ ≈ 1.12e-4 m³. The centered 102 mm × 50 mm displayed field of view over the same 10-mm thickness gives 51,000 mm³ ≈ 5.1e-5 m³. These figures exclude the larger 140 × 80 × 48 mm voxelized inversion box (67,200 voxels of 2-mm side ≈ 5.4e-4 m³), which also contains modeled skin/skull. The true curved-shell volume differs from the slab figures.",
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              "max": 0.000112,
              "note": "Flat-slab approximation of the curved 65–75 mm radius shell: 140 × 80 × 10 mm = 112,000 mm³.",
              "endpoint": "sensing_envelope"
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              "min": 0.000051,
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              "note": "Centered display region under the arrays, same 10-mm shell, flat-slab approximation: 102 × 50 × 10 mm = 51,000 mm³.",
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            "deoxyhemoglobin (HbR) concentration change"
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          "note": "Estimated indirectly from back-scattered near-infrared light attenuation, not measured directly; continuous-wave systems give only relative changes from baseline, and the recorded signal mixes cortical hemodynamics with substantial extracerebral scalp blood-flow contamination that can be mistaken for brain activity."
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          "note": "Non-invasive and non-ionizing; laser/LED exposure leaves tissue intact, and light sources must meet accepted laser or lamp photobiological safety standards."
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              "note": "Fit/place an fNIRS optode array or cap on the scalp; no surgical or genetic preparation is required."
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          "note": "Eligible across all described ages and participant groups, from premature babies and infants to patient populations, with no exclusion criteria."
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          "value": {
            "text": "Spatially, diffuse optical imaging is limited by light scattering in the head. In a modelled two-layer head, a high-density array reconstructs a point target with a point-spread FWHM of 8.2–17.2 mm depending on position (mean 12.1 mm) and a mean localization error of 1.0 mm; sparse arrays give a mean FWHM of about 21 mm. Brain sensitivity needs source-detector separations of about 3 cm, a primary factor limiting resolution.\n\nfNIRS can sample at 50 Hz (20 ms intervals); systems sampling at 10 Hz have 100 ms intervals. Sampling does not establish neural-event separation. The hemodynamic response is much slower. A proposed 0.1–1 s range of vascular oscillation periods is inferred from BOLD and is not a measured fNIRS timing limit. The shared vascular signal was demonstrated for slow event-related responses, with HbR and BOLD correlated at R = 0.98. Resolution also depends on SNR.\n\nIn coverage, sensitivity is biased toward the outer 10–15 mm of the brain. Under a spherical-brain stipulation this corresponds to a shell of about 4.4–6.6 × 10⁻⁴ m³, spanning female-to-male brain volume and 10–15 mm depth. Sensitivity is not confined to this shell; it continues to decay beyond it."
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              "id": "10.1117/1.3368999",
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              "node": "01a0e59f-7934-79f2-94eb-8015e5358ea2",
              "kind": "doi",
              "id": "10.1016/j.pneurobio.2021.102174",
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              "id": "10.1073/pnas.1608117113",
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              "node": "01a0e875-12ec-7d70-9387-2e7d8945c93c",
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              "id": "10.1186/s42492-020-00065-7",
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              "id": "10.1016/j.neuroimage.2005.08.065",
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              "id": "10.1016/j.neuroimage.2003.12.041",
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          "value": {
            "min": 0.0082,
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            "note": "Simulated diffuse-light imaging in a two-layer hemispherical head model: a high-density array reconstructs a point target with a FWHM of 8.2–17.2 mm depending on target position (mean 12.1 mm), against a mean of about 21 mm for sparse arrays. Brain sensitivity needs source-detector separations of about 3 cm, a primary factor limiting resolution.",
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                "max": 0.0172,
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                "max": 0.0121,
                "note": "12.1 ± 1.4 mm.",
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              {
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                "note": "Square and triangular sparse grids.",
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              "id": "https://pmc.ncbi.nlm.nih.gov/articles/PMC2874047/",
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        "field_of_view_m3": {
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          "value": {
            "min": 0.000443567,
            "max": 0.000660384,
            "unit": "m3",
            "note": "Using female/male V=1.11576e-3/1.23358e-3 m3 gives R=(3V/(4π))^(1/3)=0.0643419/0.0665313 m. With V_shell=4π(R²d−Rd²+d³/3), the overall range is 4.43567e-4–6.60384e-4 m3. Stipulations: the brain is spherical; shell depth is taken from the stated 10–15 mm sensitivity bias. NIRS is not confined to this shell: sensitivity continues to decay beyond it.",
            "endpoint": "sensing_envelope",
            "operating_points": [
              {
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                "min": 0.000443567,
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                "note": "Female-to-male range; d=0.010 m gives 4.43567e-4 and 4.76823e-4 m3.",
                "endpoint": "sensing_envelope"
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              {
                "label": "15 mm shell",
                "min": 0.000612564,
                "max": 0.000660384,
                "note": "Female-to-male range; d=0.015 m gives 6.12564e-4 and 6.60384e-4 m3.",
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      "slug": "fnirs-wearable",
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        "id": "optical",
        "name": "Optical & ultrasound (in vivo)"
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      "core": true,
      "summary": {
        "value": "Wearable fNIRS is near-infrared spectroscopy worn on the head, usually without fibre-optic bundles. Small light sources shine near-infrared light into the scalp and nearby detectors catch what scatters back; the change in attenuation is converted into changes in oxygenated and deoxygenated haemoglobin. These blood measures are derived from the light signal, an indirect measure of brain activity that also contains scalp blood flow. A time-domain variant times the arrival of single photons, which in one whole-head headset gave better depth sensitivity than continuous-wave systems.",
        "node": "01a150f1-f6b7-7233-9dd8-54f1520fed0d",
        "sources": [
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            "id": "10.1111/nyas.13948",
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      "description": {
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        "value": {
          "text": "Wearable fNIRS is functional near-infrared spectroscopy carried on the head, usually without fibre-optic bundles. Sources held against the scalp send near-infrared light (650 to 950 nm) into the tissue and nearby detectors collect the light that scatters back. Attenuation at two or more wavelengths changes with the concentrations of oxygenated and deoxygenated haemoglobin, so the measured quantity is a hemodynamic signal estimated from light attenuation, an indirect measure of brain activity; the recorded signal mixes cortical hemodynamics with substantial scalp blood-flow contributions. Wearable instruments are typically continuous-wave devices: battery powered, with light-emitting diodes coupled directly to the head and data stored on the unit or sent wirelessly; the absence of fibre bundles makes them lighter and less sensitive to movement. A time-domain variant records the arrival time of single photons and builds a timing histogram for each source-detector pair and wavelength. In one whole-head time-domain headset, higher moments and later time gates of that histogram kept high contrast at depths beyond 20 mm, an advantage in depth sensitivity over continuous-wave systems; changes in the absorption coefficient at each wavelength were converted to oxy- and deoxy-haemoglobin concentration changes with the modified Beer-Lambert law. That headset carries its optical modules on plates over the frontal, parietal, temporal and occipital cortices and connects to a computer by a single cable that supplies power and carries data."
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      "spatial_resolution_m": {
        "state": "known",
        "value": {
          "min": 0.013,
          "max": 0.03,
          "unit": "m",
          "note": "About 1.3 cm effective resolution for high-density diffuse optical tomography arrays; a wearable high-density system was built to match the sampling density of fibre-based ones and replicated their visual activation maps in one adult. Sparse fNIRS arrays give images with resolution on the order of 3 cm, limited by the ~3 cm source-detector separation needed for brain sensitivity."
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            "id": "10.1117/1.NPh.8.2.025002",
            "url": "https://doi.org/10.1117/1.NPh.8.2.025002"
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        "value": {
          "min": 2.0,
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          "unit": "s",
          "note": "Finest demonstrated stimulation spacing at which human fNIRS hemodynamic (HbO/HbR) responses followed the stimulus or differed by condition. These figures come from continuous-wave fNIRS systems, not from the whole-head time-domain wearable fNIRS headset. They apply to the headset only by inference: fNIRS temporal resolution is bounded by the hemodynamic response rather than by the instrument. The figures are demonstrated, not proven limits, and detectability also depends on SNR. In the 2 s Stroop design, no effect was detected at 4 s, and shorter intervals reduced oxy-Hb amplitude. The headset's own finger-tapping demonstration used 17.3 s blocks plus 20 s rest, so blocks began every 37.3 s. In that demonstration, HbO rose and HbR fell matched to the blocks, with condition-specific epoch-averaged responses. This sets only a block-level upper bound. Individual 0.75 s trials inside each block were not resolved. As context, the in-principle hemodynamic bound is a hedged 0.1–1 s, inferred from BOLD; demonstrated BOLD tracking reached about 1.33 s. The 3.76 Hz full-head cycle (about 0.27 s) and any downsampling interval are sampling intervals, not this resolution.",
          "endpoint": "recoverable_timing",
          "operating_points": [
            {
              "label": "Periodic stimulation, 0.2 Hz (continuous-wave fNIRS, prefrontal)",
              "min": 5.0,
              "max": 5.0,
              "note": "Signal showed a spectral peak at the 0.2 Hz stimulation frequency, absent without periodic stimulation.",
              "endpoint": "recoverable_timing"
            },
            {
              "label": "Event-related, shortest intertrial interval with a condition difference (continuous-wave NIRS, Stroop)",
              "min": 2.0,
              "max": 2.0,
              "note": "Deoxy-Hb decreased significantly more for incongruent than neutral trials at a 2 s intertrial interval. No effect was detected at 4 s.",
              "endpoint": "recoverable_timing"
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            "kind": "doi",
            "id": "10.1016/j.pneurobio.2021.102174",
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            "kind": "doi",
            "id": "10.1073/pnas.1608117113",
            "url": "https://doi.org/10.1073/pnas.1608117113"
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            "kind": "doi",
            "id": "10.1186/s42492-020-00065-7",
            "url": "https://doi.org/10.1186/s42492-020-00065-7"
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            "node": "01a0e87b-7b47-7720-a696-11532ca0690d",
            "kind": "doi",
            "id": "10.1016/j.neuroimage.2005.08.065",
            "url": "https://doi.org/10.1016/j.neuroimage.2005.08.065"
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            "node": "01a0e8ec-6b35-7da2-b742-fac59d435ced",
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            "id": "10.1016/j.neuroimage.2003.12.041",
            "url": "https://doi.org/10.1016/j.neuroimage.2003.12.041"
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        "value": {
          "min": 0.000444,
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          "unit": "m3",
          "note": "Conditional spherical-shell reference volume, not measured headset tissue coverage. Adult reference values: adult mean total brain volume 1.11576e-3 m3 (female) and 1.23358e-3 m3 (male); modules cover frontal, parietal, temporal and occipital cortices; NIRS sensitivity is strongly biased to the outermost 10-15 mm of the intracranial volume. Arithmetic: R=(3V/(4*pi))^(1/3) gives about 64.34 mm (female) and 66.53 mm (male). V_shell=V-(4/3)*pi*(R-d)^3. Female: d=10 mm gives 1115.76-672.2=443.6 cm3; d=15 mm gives 1115.76-503.2=612.6 cm3. Male: d=10 mm gives 1233.58-756.7=476.8 cm3; d=15 mm gives 1233.58-573.2=660.4 cm3. Stipulations: the brain is a sphere; whole-head coverage is taken as the full shell, although the modules do not literally tile the whole surface; shell depth comes from the stated sensitivity bias. Sensitivity is not strictly limited and keeps decaying exponentially beyond the shell, so the shell is only a geometric reference, not a measured sampled volume or hard sensitivity boundary.",
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            {
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              "min": 0.000444,
              "max": 0.000477,
              "note": "Female 443.6 cm3, male 476.8 cm3",
              "endpoint": "sensing_envelope"
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            {
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              "min": 0.000613,
              "max": 0.00066,
              "note": "Female 612.6 cm3, male 660.4 cm3",
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          "note": "The system records wavelength-specific photon-timing histograms. Changes in absorption at 690 and 905 nm are converted to ΔHbO and ΔHbR using wavelength-specific extinction coefficients and the modified Beer–Lambert law; hemoglobin changes are therefore derived rather than directly measured."
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          "note": "The externally worn optical headset does not penetrate, lesion, heat, or remove tissue by design. The source reports that its average power per source qualifies it as a Class 1 laser device under US FDA FLPPS 21 CFR 1040.10."
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          "note": "The headset’s fixed-module plates are joined by adjustable tensioning. It fits adult heads down to a 52 cm circumference and 32.5 cm bitragion coronal arc; no maximum is stated."
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            ]
          }
        ]
      },
      "theoretical": {
        "description": {
          "state": "known",
          "value": {
            "text": "Spatially, diffuse optical imaging is limited by light scattering in the head. In a modelled two-layer head, a high-density array reconstructs a point target with a point-spread FWHM of 8.2–17.2 mm depending on position (mean 12.1 mm) and a mean localization error of 1.0 mm; sparse arrays give a mean FWHM of about 21 mm. Brain sensitivity needs source-detector separations of about 3 cm, a primary factor limiting resolution.\n\nfNIRS can sample at 50 Hz (20 ms intervals); systems sampling at 10 Hz have 100 ms intervals. Sampling does not establish neural-event separation. The hemodynamic response is much slower. A proposed 0.1–1 s range of vascular oscillation periods is inferred from BOLD and is not a measured fNIRS timing limit. The shared vascular signal was demonstrated for slow event-related responses, with HbR and BOLD correlated at R = 0.98. Resolution also depends on SNR.\n\nIn coverage, sensitivity is biased toward the outer 10–15 mm of the brain. Under a spherical-brain stipulation this corresponds to a shell of about 4.4–6.6 × 10⁻⁴ m³, spanning female-to-male brain volume and 10–15 mm depth. Sensitivity is not confined to this shell; it continues to decay beyond it."
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              "url": "https://doi.org/10.1111/nyas.13948"
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              "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC2874047/"
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              "id": "10.1371/journal.pone.0066319",
              "url": "https://doi.org/10.1371/journal.pone.0066319"
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              "url": "https://doi.org/10.1117/1.3368999"
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              "node": "01a0e59f-7934-79f2-94eb-8015e5358ea2",
              "kind": "doi",
              "id": "10.1016/j.pneurobio.2021.102174",
              "url": "https://doi.org/10.1016/j.pneurobio.2021.102174"
            },
            {
              "node": "01a0e5a2-42c9-7203-b72c-40a33a13a2d0",
              "kind": "doi",
              "id": "10.1073/pnas.1608117113",
              "url": "https://doi.org/10.1073/pnas.1608117113"
            },
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              "node": "01a0e875-12ec-7d70-9387-2e7d8945c93c",
              "kind": "doi",
              "id": "10.1186/s42492-020-00065-7",
              "url": "https://doi.org/10.1186/s42492-020-00065-7"
            },
            {
              "node": "01a0e87b-7b47-7720-a696-11532ca0690d",
              "kind": "doi",
              "id": "10.1016/j.neuroimage.2005.08.065",
              "url": "https://doi.org/10.1016/j.neuroimage.2005.08.065"
            },
            {
              "node": "01a0e8ec-6b35-7da2-b742-fac59d435ced",
              "kind": "doi",
              "id": "10.1016/j.neuroimage.2003.12.041",
              "url": "https://doi.org/10.1016/j.neuroimage.2003.12.041"
            }
          ]
        },
        "spatial_resolution_m": {
          "state": "known",
          "value": {
            "min": 0.0082,
            "max": 0.0082,
            "unit": "m",
            "note": "Simulated diffuse-light imaging in a two-layer hemispherical head model: a high-density array reconstructs a point target with a FWHM of 8.2–17.2 mm depending on target position (mean 12.1 mm), against a mean of about 21 mm for sparse arrays. Brain sensitivity needs source-detector separations of about 3 cm, a primary factor limiting resolution.",
            "endpoint": "point_spread",
            "operating_points": [
              {
                "label": "High-density array, target-position range",
                "min": 0.0082,
                "max": 0.0172,
                "note": "Variation across modeled point-target positions.",
                "endpoint": "point_spread"
              },
              {
                "label": "High-density array, mean point-spread FWHM",
                "min": 0.0121,
                "max": 0.0121,
                "note": "12.1 ± 1.4 mm.",
                "endpoint": "point_spread"
              },
              {
                "label": "High-density array, localization error",
                "min": 0.0,
                "max": 0.0058,
                "note": "Mean 1.0 ± 0.9 mm across target positions.",
                "endpoint": "localisation_error"
              },
              {
                "label": "Sparse arrays, mean point-spread FWHM",
                "min": 0.0209,
                "max": 0.0216,
                "note": "Square and triangular sparse grids.",
                "endpoint": "point_spread"
              }
            ]
          },
          "node": "01a16641-de21-75b0-9f3c-e4104a0666b7",
          "sources": [
            {
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              "kind": "url",
              "id": "https://pmc.ncbi.nlm.nih.gov/articles/PMC2874047/",
              "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC2874047/"
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              "id": "10.1117/1.3368999",
              "url": "https://doi.org/10.1117/1.3368999"
            }
          ]
        },
        "temporal_resolution_s": {
          "state": "known",
          "value": {
            "min": 0.1,
            "max": 1.0,
            "unit": "s",
            "note": "The in-principle temporal resolution of fNIRS is bounded by the hemodynamic response, not by the instrument. By extension from fMRI, it spans a hedged 0.1–1 s, which is not an established interval. Simultaneous NIRS-BOLD recordings during an event-related motor task found HbR correlated with BOLD (R = 0.98), supporting similar vascular sensitivity. The 0.1 s end is an expectation that vasculature is unlikely to follow neural oscillations above 10 Hz, not a measured bound. The 1 s end reflects BOLD perhaps tracking oscillations up to 1 Hz in human visual cortex; demonstrated tracking reached 0.75 Hz (period about 1.33 s). fNIRS sampling up to 10 Hz oversamples the response, and the roughly 6 s response peak is a duration rather than a resolution. Resolution depends on SNR. The shared time course was shown only for slow event-related responses, so the fast limits transfer to fNIRS by inference, not by direct measurement.",
            "operating_points": [
              {
                "label": "Vasculature unlikely to follow (>10 Hz)",
                "min": 0.1,
                "max": 0.1,
                "note": "Period 1/f for 10 Hz; this is an expectation, not a measured bound. It coincides with the 10 Hz fNIRS sampling interval, which is not itself a resolution."
              },
              {
                "label": "Highest frequency hemodynamics perhaps tracked (1 Hz, BOLD in human visual cortex)",
                "min": 1.0,
                "max": 1.0,
                "note": "Hedged ('perhaps even 1 Hz'). Demonstrated tracking reached 0.75 Hz (period about 1.33 s) with BOLD at 7 T. This transfers to fNIRS via the shared hemodynamic signal."
              }
            ]
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              "url": "https://doi.org/10.1111/nyas.13948"
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              "kind": "doi",
              "id": "10.1016/j.pneurobio.2021.102174",
              "url": "https://doi.org/10.1016/j.pneurobio.2021.102174"
            },
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              "kind": "doi",
              "id": "10.1073/pnas.1608117113",
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              "kind": "doi",
              "id": "10.1016/j.neuroimage.2005.08.065",
              "url": "https://doi.org/10.1016/j.neuroimage.2005.08.065"
            }
          ]
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        "field_of_view_m3": {
          "state": "known",
          "value": {
            "min": 0.000443567,
            "max": 0.000660384,
            "unit": "m3",
            "note": "Using female/male V=1.11576e-3/1.23358e-3 m3 gives R=(3V/(4π))^(1/3)=0.0643419/0.0665313 m. With V_shell=4π(R²d−Rd²+d³/3), the overall range is 4.43567e-4–6.60384e-4 m3. Stipulations: the brain is spherical; shell depth is taken from the stated 10–15 mm sensitivity bias. NIRS is not confined to this shell: sensitivity continues to decay beyond it.",
            "endpoint": "sensing_envelope",
            "operating_points": [
              {
                "label": "10 mm shell",
                "min": 0.000443567,
                "max": 0.000476823,
                "note": "Female-to-male range; d=0.010 m gives 4.43567e-4 and 4.76823e-4 m3.",
                "endpoint": "sensing_envelope"
              },
              {
                "label": "15 mm shell",
                "min": 0.000612564,
                "max": 0.000660384,
                "note": "Female-to-male range; d=0.015 m gives 6.12564e-4 and 6.60384e-4 m3.",
                "endpoint": "sensing_envelope"
              }
            ]
          },
          "node": "01a1513e-7210-7c31-89b3-b37fefe9f7e8",
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              "url": "https://doi.org/10.1093/cercor/bhy109"
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              "kind": "doi",
              "id": "10.1371/journal.pone.0066319",
              "url": "https://doi.org/10.1371/journal.pone.0066319"
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      "name": "Fast-scan cyclic voltammetry",
      "group": {
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        "name": "Chemical sensing"
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          "min": 0.1,
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          "unit": "s",
          "note": "Subsecond, routinely a 10 Hz repetition (0.1 s); the ~8-10 ms waveform could repeat near 100 Hz but signal falls >75% there."
        },
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            "url": "https://doi.org/10.3389/fbioe.2025.1569508"
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            "id": "10.3389/fnins.2021.728092",
            "url": "https://doi.org/10.3389/fnins.2021.728092"
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        "items": [
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              "label": "Pinnacle Carbon Fiber Electrode (34 um diameter, 0.5 mm long; fixed version same price)"
            },
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            "sources": [
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      "name": "Focused ultrasound (FUS) blood–brain barrier opening",
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        "value": "Focused-ultrasound blood-brain barrier opening is image-guided sonication at low acoustic pressure, delivered together with injected gas-filled microbubbles. The sound makes the microbubbles in the capillaries expand and contract, and the resulting mechanical forces open the blood-brain barrier in the targeted region for a limited time, without open surgery; that opening is what it writes. What it reads is not brain activity: acoustic cavitation feedback and MR-derived temperature during sonication, patient feedback, and afterwards gadolinium-enhanced MRI as a surrogate for barrier permeability.",
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          "text": "Focused-ultrasound blood-brain barrier opening is image-guided sonication at low acoustic pressure delivered with injected gas-filled microbubbles. The sound makes the microbubbles in the capillaries expand and contract (stable cavitation); the resulting mechanical forces open the barrier in the targeted region without open surgery. The opening is transient, reversible and repeatable; in a human brain-tumour study, post-sonication enhancement of the target region resolved by 24 hours. A reviewed pressure window of 0.4 to 1.2 MPa opened the barrier safely; higher pressures can trigger damaging inertial cavitation. In one MR-guided patient study, power rose in 5% steps until hydrophones detected sub-harmonic acoustic feedback, with MR thermometry and patient feedback monitored during sonication. In a 220 kHz trial, power rose until an accumulated cavitation dose of 0.4 to 0.65 was reached, and sonication stopped when inertial cavitation was confirmed. Both verified the opening afterwards with gadolinium-enhanced MRI, a surrogate for barrier permeability."
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          "unit": "m",
          "note": "Approximate extents of the simulated 50% isopressure focal region, inferred from a similarly sized 4 × 4 × 10 mm ellipsoidal ROI.",
          "endpoint": "focal_extent",
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            {
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              "note": "Two equivalent lateral dimensions of the ellipsoid.",
              "endpoint": "focal_extent"
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          "note": "Pulse onsets every 30 ms within a 300 ms train in the human focused-ultrasound BBB-opening protocol: 2 ms on plus 28 ms off. Grid-site trains repeat at 2.7 s intervals. This is ultrasound delivery timing, not independent repeated barrier opening or closure.",
          "endpoint": "inter_pulse_interval",
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              "note": "Closure within 24 h in the human study.",
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      "field_of_view_m3": {
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        "value": {
          "min": 3.5e-7,
          "max": 0.0000211,
          "unit": "m3",
          "note": "Per-session volume, spanning a fully permeabilized target and a larger mean target with opening confirmed in 95.7%.",
          "endpoint": "treated_volume",
          "operating_points": [
            {
              "label": "Permeabilized total target",
              "min": 3.5e-7,
              "max": 3.5e-7,
              "note": "350 mm^3 total target volume was permeabilized.",
              "endpoint": "treated_volume"
            },
            {
              "label": "Bilateral frontal Alzheimer’s disease target",
              "min": 0.0000211,
              "max": 0.0000211,
              "note": "Mean targeted volume was 21.1 cm^3; BBB opening was confirmed in 95.7% of it.",
              "endpoint": "treated_volume"
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        "node": "01a15119-4982-73b2-a919-b4171e019a00",
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          "measurands": [
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            "gadolinium-enhanced MRI signal"
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          "note": "Acoustic feedback/dose guides power escalation and stopping; temperature and patient feedback are monitored during sonication. Post-sonication MRI enhancement confirms opening, but is a surrogate for BBB permeability."
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        "value": {
          "stimuli": [
            "Focused ultrasound sonication",
            "Microbubbles"
          ],
          "note": "Together they drive stable microbubble cavitation and mechanical forces in capillary lumens, producing transient, targeted, reversible BBB opening."
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            "id": "10.3389/fphy.2020.547674",
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        "value": {
          "kind": "non_destructive",
          "note": "FUS-BBB opening is reported as transient and reversible, without persistent lesions or significant tissue damage. Possible microhemorrhage-like MRI findings resolved by 24 h; no hemorrhage was detected in another trial, and one asymptomatic FLAIR hyperintensity resolved by 30 days."
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          "steps": [
            {
              "kind": "other",
              "note": "Fix a CRW stereotactic frame to the patient’s head."
            },
            {
              "kind": "anesthesia",
              "note": "Administer local anesthetic for head-frame fixation."
            },
            {
              "kind": "contrast_agent",
              "note": "Inject microbubbles."
            }
          ],
          "note": "The described FUS-BBB opening protocol requires stereotactic head-frame fixation under local anesthetic and microbubble injection."
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          "value": {
            "text": "An ideal half-wavelength focus gives about 0.75 mm at 1 MHz and 1.5 mm at 0.5 MHz, assuming waves converge from all directions; the skull scatters strongly above 1 MHz. Virtually any brain region can be targeted. The 1.23358 × 10⁻³ m³ whole-brain value is a conventional large-brain reference, not measured device reach or the volume opened in a sonication."
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            "note": "In-principle ideal half-wavelength focal size for transcranial focused ultrasound. Arithmetic: wavelength ≈ 3 mm at 0.5 MHz, so λ/2 ≈ 1.5 mm = 0.0015 m. Assuming wavelength scales as 1/frequency (constant sound speed), λ ≈ 1.5 mm at 1 MHz, so λ/2 ≈ 0.75 mm = 0.00075 m. 1 MHz is the practical upper bound because the skull scatters strongly above 1 MHz. Caveats: this is an idealized bound that assumes waves converge from all directions; the 3 mm wavelength is approximate; practical resolution is only 'on the order of' the wavelength.",
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              {
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                "note": "λ ≈ 3 mm × (0.5/1) = 1.5 mm; λ/2 ≈ 0.75 mm. This is the finest case, since the skull scatters strongly above 1 MHz."
              },
              {
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            "note": "Virtually any brain region can be targeted. This reachable volume is the larger adult mean total brain volume used as a conventional reference size for a large brain, not a measured device reach, and is not the volume opened in one sonication.",
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    {
      "slug": "fus-imaging",
      "name": "Functional ultrasound (fUS)",
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        "id": "optical",
        "name": "Optical & ultrasound (in vivo)"
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        "value": "Functional ultrasound is an imaging method that sends ultrasound plane waves into the brain 1,000 times a second; the Power Doppler signal this yields is proportional to the volume of moving blood in small vessels. What it reads is cerebral blood volume, and because blood volume follows neural activity through neurovascular coupling, the activity is inferred indirectly. In the intraoperative setup only vessels with axial flow above 4 mm/s contributed. In humans it reaches the brain during brain surgery, at 250 µm, and in newborns through the anterior fontanel.",
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      "description": {
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        "value": {
          "text": "Functional ultrasound (fUS) is an imaging method that maps brain activity through its blood supply with ultrafast ultrasound. In the intraoperative setup plane waves are transmitted at a frame rate of 1 kHz; the Power Doppler signal is proportional to the fractional volume of moving blood in small vessels; in the intraoperative setup, only vessels with axial flow above 4 mm/s contributed. The image tracks cerebral blood volume (CBV) over time. CBV changes follow neuronal activity through neurovascular coupling, so the activity is inferred indirectly. Functional connectivity is derived from temporal correlations between CBV changes in distant regions. The maps reach deep within the cortex, including the sulci. In adults, fUS reaches the brain during brain surgery, imaging transient CBV changes at 250 µm; each Doppler acquisition spans one heart cycle (1 s) at the 1 kHz frame rate and is repeated every 3 s. In newborns, a miniaturized linear probe anchored in a 3D-printed headset images through the anterior fontanel, where the imaging depth reached 49 mm after optimization, covering more than 40% of the neonatal brain volume. In rodents, rats are imaged at 100 µm × 100 µm in-plane resolution with 200 µm slices, and mice through a cranial window in which an ultrasound-permeable polymer film replaces a dorsal section of skull (about 8 mm × 5 mm), with a 15 MHz linear array producing a power Doppler image every 300 ms."
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          "note": "100 um in-plane (200 um slice) in rats; 250 um in intraoperative human and neonatal transfontanel imaging."
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        "value": {
          "min": 0.3,
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          "note": "Awake mice imaged at 15 MHz: power Doppler images every 300 ms (3.33 Hz), each averaged from continuous 500 Hz Doppler data. fUSI tracked firing rate coherently only below 0.32 Hz, so this is a sample interval, not a recoverable timing. Human neonatal and earlier protocols produced functional frames 1–3 s apart.",
          "endpoint": "sample_interval",
          "operating_points": [
            {
              "label": "Neonatal protocol",
              "min": 1.0,
              "max": 1.0,
              "note": "One power Doppler frame per second, each from a 342-image stack at 600 Hz over 570 ms.",
              "endpoint": "sample_interval"
            },
            {
              "label": "Acquisitions repeated every 3 s",
              "min": 3.0,
              "max": 3.0,
              "note": "200 compound images at 1 kHz per acquisition.",
              "endpoint": "sample_interval"
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        "node": "01a15cfa-7259-7822-a9e9-5dc74b4420ff",
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      "field_of_view_m3": {
        "state": "known",
        "value": {
          "min": 0.0000555556,
          "max": 0.0000555556,
          "unit": "m3",
          "note": "Nominal reconstructed volume for the human 4D functional ultrasound prototype (3072-element probe), whose volumes were reconstructed in a spherical domain spanning 60° × 60° × 50 mm. The value assumes the stipulated right-pyramid idealization of that domain. It is not a measured activated-tissue volume and not a general linear-probe field of view.",
          "endpoint": "acquired_volume"
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        "state": "known",
        "value": {
          "measurands": [
            "power-Doppler signal intensity",
            "cerebral blood volume"
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          "note": "Power-Doppler intensity is proportional to moving/fractional cerebral blood volume. Neural activity is inferred indirectly from CBV changes via neurovascular coupling; one cited setup detected only axial flow above 4 mm/s."
        },
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            "url": "https://doi.org/10.34133/research.0200"
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        ]
      },
      "stimulation": {
        "state": "incomplete"
      },
      "destructiveness": {
        "state": "known",
        "value": {
          "kind": "non_destructive",
          "note": "Low-output plane-wave imaging; no invasive penetration, lesioning, heating, or removal is reported as intended. ISPTA was 30 vs 720 mW/cm² and MI 0.5 vs 1.9; TI was 0.5. No side effects were reported, but no temperature or histology test proves zero harm."
        },
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          },
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            "node": "01a0590c-dd82-7cd0-bcf1-beedcf8d75f9",
            "kind": "doi",
            "id": "10.1002/jum.70085",
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            "id": "https://www.fda.gov/media/71100/download",
            "url": "https://www.fda.gov/media/71100/download"
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        "value": {
          "steps": [
            {
              "kind": "other",
              "note": "Neonatal fontanelle: place and stabilize a miniaturized probe in a headset over the anterior fontanelle; no invasive preparation is described."
            },
            {
              "kind": "surgery",
              "note": "Intraoperative route: open the skull and dura before fUS imaging."
            },
            {
              "kind": "surgery",
              "note": "Prosthesis/window route: surgically place a sonolucent cranial prosthesis or window for subsequent imaging."
            }
          ],
          "note": "Preparation depends on the acoustic-window route."
        },
        "node": "01a0d90d-5079-7360-b464-9fe586c3fd20",
        "sources": [
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            "node": "01a0548b-f02d-7b62-a70a-e6a8dd1bf655",
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            "id": "10.1038/nmeth.1641",
            "url": "https://doi.org/10.1038/nmeth.1641"
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            "kind": "doi",
            "id": "10.1038/s41598-017-06474-8",
            "url": "https://doi.org/10.1038/s41598-017-06474-8"
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            "kind": "doi",
            "id": "10.34133/research.0200",
            "url": "https://doi.org/10.34133/research.0200"
          }
        ]
      },
      "cost": {
        "state": "known",
        "items": [
          {
            "value": {
              "kind": "instrument",
              "currency": "USD",
              "amount_min": 116737.28,
              "year": 2013,
              "label": "Verasonics ultrasound system, federal contract award signed 2013-08-22, total obligation (contract value, not vendor list price)"
            },
            "node": "01a09201-ed99-7fe3-aff0-2d621e7e1dd7",
            "sources": [
              {
                "node": "01a073f5-3bcd-76c2-8a8f-9ceee62f81a3",
                "kind": "url",
                "id": "https://api.usaspending.gov/api/v2/awards/CONT_AWD_HHSF223201300679P_7524_-NONE-_-NONE-/",
                "url": "https://api.usaspending.gov/api/v2/awards/CONT_AWD_HHSF223201300679P_7524_-NONE-_-NONE-/"
              }
            ]
          }
        ]
      },
      "theoretical": {
        "description": {
          "state": "known",
          "value": {
            "text": "At 15 MHz, the wavelength-order diffraction limit is 100 μm. Depth and resolution trade against each other through frequency: the 5–8 cm reach comes from a 5 MHz-centre human probe, so it is not obtained at the 100 μm figure. A 60°×60° field idealized as a right square pyramid spans 5.56×10⁻⁵ m³ at 5 cm or at most 2.28×10⁻⁴ m³ at 8 cm with direct cortical contact, supporting detailed cortical mapping rather than fMRI-like whole-brain coverage.\n\nA demonstrated image sample interval is 0.3 s. The biological response is slower: ~1 s FWHM in rodents after a single 333-μs forelimb stimulus (0.35 s onset; ~1 s peak), and 2.9 ± 0.6 s FWHM for the firing-rate-to-fUSI response in 34 experiments across five mice (2.1 ± 0.3 s peak delay)."
          },
          "node": "01a16a3e-e44d-7211-b537-f564b2d07d5c",
          "sources": [
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              "url": "https://doi.org/10.1038/s41467-021-21387-x"
            },
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              "kind": "doi",
              "id": "10.1038/nmeth.1641",
              "url": "https://doi.org/10.1038/nmeth.1641"
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              "kind": "doi",
              "id": "10.1038/s41598-017-06474-8",
              "url": "https://doi.org/10.1038/s41598-017-06474-8"
            },
            {
              "node": "01a0d911-26ec-7063-8968-6fdf5cac08ed",
              "kind": "doi",
              "id": "10.1101/2025.08.19.25332261",
              "url": "https://doi.org/10.1101/2025.08.19.25332261"
            },
            {
              "node": "01a0e107-c994-7330-8b2e-ac13f24ab74b",
              "kind": "doi",
              "id": "10.1016/j.neuron.2020.09.003",
              "url": "https://doi.org/10.1016/j.neuron.2020.09.003"
            },
            {
              "node": "01a0e115-201f-7313-afa3-ccb985eb73a9",
              "kind": "doi",
              "id": "10.1016/j.neuron.2022.02.012",
              "url": "https://doi.org/10.1016/j.neuron.2022.02.012"
            },
            {
              "node": "01a0e310-0a20-7291-822f-51e1054fca3e",
              "kind": "doi",
              "id": "10.1523/jneurosci.3986-10.2011",
              "url": "https://doi.org/10.1523/jneurosci.3986-10.2011"
            }
          ]
        },
        "spatial_resolution_m": {
          "state": "known",
          "value": {
            "min": 0.0001,
            "max": 0.0001,
            "unit": "m",
            "note": "Order-of-wavelength diffraction limit, derived by interpolating the source's stated inverse frequency–wavelength correspondence to 15 MHz.",
            "operating_points": [
              {
                "label": "15 MHz",
                "min": 0.0001,
                "max": 0.0001,
                "note": "Corresponds to a wavelength of 100 μm in soft tissue."
              }
            ]
          },
          "node": "01a0e149-00c1-7622-96bd-0e13d2ad0480",
          "sources": [
            {
              "node": "01a0e107-c994-7330-8b2e-ac13f24ab74b",
              "kind": "doi",
              "id": "10.1016/j.neuron.2020.09.003",
              "url": "https://doi.org/10.1016/j.neuron.2020.09.003"
            }
          ]
        },
        "temporal_resolution_s": {
          "state": "incomplete"
        },
        "field_of_view_m3": {
          "state": "known",
          "value": {
            "min": 0.00005556,
            "max": 0.00022756,
            "unit": "m3",
            "note": "Idealized as a right square pyramid with a 60°×60° aperture, V=(4/9)h³, stipulating the stated depths of a 5 MHz-centre human probe: 5 cm through cranial windows or sonolucent implants, 8 cm with direct cortical contact. This is detailed cortical mapping, not fMRI-like whole-brain coverage. The 100 µm diffraction limit belongs to 15 MHz imaging, where the wavelength is shorter, so this reach and that resolution are not obtained together.",
            "endpoint": "reachable_envelope",
            "operating_points": [
              {
                "label": "8 cm, direct cortical contact, 5 MHz probe",
                "min": 0.00022756,
                "max": 0.00022756,
                "note": "V=(4/9)(0.08 m)³.",
                "endpoint": "reachable_envelope"
              },
              {
                "label": "5 cm, cranial window or sonolucent implant, 5 MHz probe",
                "min": 0.00005556,
                "max": 0.00005556,
                "note": "V=(4/9)(0.05 m)³.",
                "endpoint": "reachable_envelope"
              }
            ]
          },
          "node": "01a15d26-4234-7152-8df9-a7084c18c6a8",
          "sources": [
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              "url": "https://doi.org/10.1101/2025.08.19.25332261"
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              "kind": "doi",
              "id": "10.1016/j.neuron.2020.09.003",
              "url": "https://doi.org/10.1016/j.neuron.2020.09.003"
            }
          ]
        },
        "field_of_view_neurons": {
          "state": "incomplete"
        }
      }
    },
    {
      "slug": "gamma-knife",
      "name": "Gamma Knife radiosurgery",
      "group": {
        "id": "stim-noninvasive",
        "name": "Non-invasive write"
      },
      "mode": "write",
      "core": true,
      "summary": {
        "value": "Gamma Knife radiosurgery is a device holding sealed cobalt-60 sources (192 in one version, 201 in another) whose gamma rays pass through circular tungsten openings, with nominal collimator sizes of 4, 8 or 16 mm, directing the radiation to a single focus. By combining several focal points and collimator sizes, it delivers a radiation dose shaped to a three-dimensional target in the head. Target coordinates come from markers on a head frame or from built-in cone-beam CT imaging, while a frame or mask holds the head still. For a 4 mm Perfexion collimator, the single-shot dose-profile FWHM is 5.04–6.16 mm across axes in the planning system and an ellipsoid model.",
        "node": "01a16d12-6dae-7ad1-b84a-35b0b24bcc22",
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            "id": "10.1371/journal.pone.0306159",
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            "id": "10.3349/ymj.2020.61.2.111",
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            "url": "https://doi.org/10.1120/jacmp.v17i4.6196"
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            "node": "01a0e311-8c82-7382-9e65-f61674162e7c",
            "kind": "url",
            "id": "https://wfns.org/WFNSData/Document/ClinicalResources/Gamma_Knife_Radiosurgery.pdf",
            "url": "https://wfns.org/WFNSData/Document/ClinicalResources/Gamma_Knife_Radiosurgery.pdf"
          },
          {
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            "id": "10.3340/jkns.2020.0186",
            "url": "https://doi.org/10.3340/jkns.2020.0186"
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      "row_node": "01a16d1b-1bcf-7a73-909a-173be26987d9",
      "description": {
        "state": "known",
        "value": {
          "text": "Gamma Knife radiosurgery is stereotactic treatment of a small intracranial target with many thin beams of gamma radiation from sealed cobalt-60 sources, all converging on one focus. The beams converge on the target, which keeps the damage to the surrounding tissue to a minimum. In the Icon unit, 192 sources are arranged in eight motorized sectors; to treat, the sectors move over a circular tungsten collimator with nominal collimator sizes of 4, 8 or 16 mm, so that every beam points at a single radiative focus. The older Model B has 201 sources. A treatment plan usually combines one or more isocenters (focus positions) using different collimator sizes to conform the dose to the three-dimensional volume of the target; the number of isocenters depends on the size, shape and location of the target. For a trigeminal nerve target, the proposed rationale for pain relief is focal axonal degeneration of the nerve, destruction of ion channels, and electrophysiological blocking soon after irradiation. Target coordinates come from a stereotactic image set: coordinates derived from a fiducial indicator box on a stereotactic head frame (the G-frame) in framed workflows, or on-board cone-beam CT in frameless workflows, which use a mask made for the patient. The Icon unit adds cone-beam CT and intra-fraction motion management to the Perfexion design. The mechanical treatment range of the Perfexion unit is 160, 180 and 220 mm along X, Y and Z, against 100, 120 and 165 mm for earlier models. For the 4 mm Perfexion collimator, the single-shot dose-profile FWHM is 5.04–6.16 mm across axes in the planning system and an ellipsoid model."
        },
        "node": "01a16d12-6d97-7002-8111-a4f70515c0c1",
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            "id": "https://wfns.org/WFNSData/Document/ClinicalResources/Gamma_Knife_Radiosurgery.pdf",
            "url": "https://wfns.org/WFNSData/Document/ClinicalResources/Gamma_Knife_Radiosurgery.pdf"
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      "spatial_resolution_m": {
        "state": "known",
        "value": {
          "min": 0.00504,
          "max": 0.00616,
          "unit": "m",
          "note": "FWHM of the 4 mm single-shot dose profile on Gamma Knife Perfexion, from the Leksell GammaPlan planning system and a modified variable-ellipsoid model. Perfexion collimators are 4, 8 and 16 mm; model 4C collimators are 4, 8, 14 and 18 mm; 4 mm is the smallest in both. No 4 mm FWHM is given for model 4C, only a single-beam 80–20% penumbra of 0.75 mm along X, which is a different quantity.",
          "endpoint": "focal_extent",
          "operating_points": [
            {
              "label": "z-axis (Perfexion, 4 mm)",
              "min": 0.00504,
              "max": 0.00516,
              "note": "5.04 mm by the planning system and 5.16 mm by the ellipsoid model; this is the narrowest axis.",
              "endpoint": "focal_extent"
            },
            {
              "label": "x- and y-axes (Perfexion, 4 mm)",
              "min": 0.0061,
              "max": 0.00616,
              "note": "6.10 mm by the ellipsoid model and 6.16 mm by the planning system, identical for x and y.",
              "endpoint": "focal_extent"
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      "temporal_resolution_s": {
        "state": "unknown",
        "value": {
          "reason": "Gamma Knife radiosurgery has no repeatable independently timed neural effects."
        },
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        "value": {
          "min": 4.4e-8,
          "max": 0.0000199,
          "unit": "m3",
          "note": "Treated tumor volume for Gamma-Knife-treated brain metastases; full reported range of 0.044–19.9 cm3.",
          "endpoint": "treated_volume",
          "operating_points": [
            {
              "label": "Median tumor volume",
              "min": 2.5e-6,
              "max": 2.5e-6,
              "note": "Reported median of 2.50 cm3.",
              "endpoint": "treated_volume"
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      "field_of_view_neurons": {
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      "measurand": {
        "state": "unknown",
        "value": {
          "reason": "Gamma Knife radiosurgery applies focused cobalt-60 gamma radiation; its CT/MRI/CBCT imaging defines stereotactic coordinates rather than reading a signal or response from brain tissue."
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          "unit": "m",
          "note": "The focal spot of the Exablate Neuro transducer measured with a hydrophone in water (bench testing for PMA P150038), stated as spot dimensions of 1.3 x 1.3 x 2.6 mm; this is the acoustic focus without a skull in the path, not a lesion. In MR-guided focused-ultrasound thalamotomy the lesions themselves are larger: a goal lesion of at least 4 mm, and a region of ablation typically 6-8 mm on T2-weighted imaging 24 h after treatment, with specifics varying by time interval and MRI method.",
          "endpoint": "focal_extent",
          "operating_points": [
            {
              "label": "Focal spot in water, two transverse dimensions",
              "min": 0.0013,
              "max": 0.0013,
              "note": "1.3 mm, hydrophone bench measurement.",
              "endpoint": "focal_extent"
            },
            {
              "label": "Focal spot in water, third dimension",
              "min": 0.0026,
              "max": 0.0026,
              "note": "2.6 mm, hydrophone bench measurement.",
              "endpoint": "focal_extent"
            },
            {
              "label": "Goal-lesion criterion, thalamotomy",
              "min": 0.004,
              "max": 0.004,
              "note": "Minimum goal lesion 4 mm.",
              "endpoint": "suprathreshold_extent"
            },
            {
              "label": "Typical 24-h ablation region, thalamotomy",
              "min": 0.006,
              "max": 0.008,
              "note": "6-8 mm on T2-weighted imaging.",
              "endpoint": "suprathreshold_extent"
            }
          ]
        },
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            "id": "10.3389/fneur.2024.1370574",
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            "kind": "doi",
            "id": "10.3389/fneur.2023.1272425",
            "url": "https://doi.org/10.3389/fneur.2023.1272425"
          }
        ]
      },
      "temporal_resolution_s": {
        "state": "known",
        "value": {
          "min": 300.0,
          "unit": "s",
          "note": "At least 300 s between sonication onsets in the cited prospective intracranial thermoablation protocol, because it prescribes 5 min of cooling between sonications; onset spacing additionally includes the preceding sonication duration. This is a protocol-specific lower bound, not an observed minimum or a physical limit.",
          "endpoint": "inter_pulse_interval",
          "operating_points": [
            {
              "label": "Sonications in a separate clinical series",
              "min": 10.0,
              "max": 39.0,
              "note": "Individual sonication durations; not the cooling interval.",
              "endpoint": "pulse_width"
            }
          ]
        },
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            "node": "01a0c5b9-b50b-7e01-9af5-ec05c1033741",
            "kind": "doi",
            "id": "10.1155/2018/9764807",
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            "kind": "url",
            "id": "https://cdn.clinicaltrials.gov/large-docs/78/NCT07497178/Prot_SAP_000.pdf",
            "url": "https://cdn.clinicaltrials.gov/large-docs/78/NCT07497178/Prot_SAP_000.pdf"
          }
        ]
      },
      "field_of_view_m3": {
        "state": "known",
        "value": {
          "min": 3.025e-7,
          "max": 4.358e-7,
          "unit": "m3",
          "note": "Mean MRgFUS thalamotomy lesion volume across skull-density-ratio groups (302.5 mm^3 to 435.8 mm^3); patients without a goal lesion of at least 4 mm were excluded.",
          "endpoint": "treated_volume"
        },
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      "field_of_view_neurons": {
        "state": "incomplete"
      },
      "measurand": {
        "state": "known",
        "value": {
          "measurands": [
            "tissue temperature"
          ],
          "note": "The technique drives focused high-intensity ultrasound energy that heats tissue to coagulative thermal ablation, with the target temperature and lesion formation monitored in real time via MR thermometry rather than a measurement of neural activity."
        },
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            "kind": "url",
            "id": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5963668/",
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            "id": "10.3389/fneur.2025.1659203",
            "url": "https://doi.org/10.3389/fneur.2025.1659203"
          }
        ]
      },
      "stimulation": {
        "state": "known",
        "value": {
          "stimuli": [
            "focused acoustic energy"
          ],
          "note": "The technique drives focused high-intensity ultrasound energy that heats tissue to coagulative thermal ablation, with the target temperature and lesion formation monitored in real time via MR thermometry rather than a measurement of neural activity."
        },
        "node": "01a0d3b8-8db6-75e3-8955-09d7139148da",
        "sources": [
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            "id": "10.3389/fneur.2025.1659203",
            "url": "https://doi.org/10.3389/fneur.2025.1659203"
          }
        ]
      },
      "destructiveness": {
        "state": "known",
        "value": {
          "kind": "destructive",
          "note": "High-intensity transcranial focused ultrasound thermally ablates and permanently destroys the targeted brain tissue by design (e.g. thalamotomy, tumor ablation); this is distinct from low-intensity ultrasound neuromodulation, which does not destroy tissue."
        },
        "node": "01a0abb1-fee0-7ab2-b2e0-23abb9d6c4e3",
        "sources": [
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            "node": "01a054a3-ed2f-7e23-86bd-e20499df37a0",
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          },
          {
            "node": "01a054a4-0f0d-77c3-9887-5264c78b6515",
            "kind": "doi",
            "id": "10.3389/fneur.2019.00549",
            "url": "https://doi.org/10.3389/fneur.2019.00549"
          }
        ]
      },
      "preparation": {
        "state": "known",
        "value": {
          "steps": [
            {
              "kind": "other",
              "note": "Shave the patient’s head."
            },
            {
              "kind": "other",
              "note": "Secure a stereotactic frame low on the patient’s head."
            }
          ],
          "note": "MRgFUS is noninvasive, requiring no craniotomy or incision, and uses real-time MRI for targeting."
        },
        "node": "01a0b334-545d-7a91-90d3-5695b6e28e08",
        "sources": [
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            "node": "01a054b6-5a28-7b00-8aca-ddee0def70ce",
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            "node": "01a054e2-0ab6-72c0-8d50-a3de3161a84c",
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            "id": "10.3389/fneur.2024.1370574",
            "url": "https://doi.org/10.3389/fneur.2024.1370574"
          }
        ]
      },
      "cost": {
        "state": "known",
        "items": [
          {
            "value": {
              "kind": "procedure",
              "currency": "CAD",
              "amount_min": 23507.0,
              "amount_max": 23507.0,
              "year": 2017,
              "label": "MRgFUS neurosurgery: modeled mean cost (cost-utility model)"
            },
            "node": "01a0abb2-a096-7071-9df1-428f7e6eefb1",
            "sources": [
              {
                "node": "01a054b6-5a28-7b00-8aca-ddee0def70ce",
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                "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5963668/"
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            ]
          },
          {
            "value": {
              "kind": "procedure",
              "currency": "CAD",
              "amount_min": 19786.0,
              "amount_max": 19786.0,
              "year": 2017,
              "label": "MRgFUS neurosurgery: mean total cost per procedure"
            },
            "node": "01a0abb2-abce-7432-9b5b-14e7282198ab",
            "sources": [
              {
                "node": "01a054b6-5a28-7b00-8aca-ddee0def70ce",
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          {
            "value": {
              "kind": "instrument",
              "currency": "USD",
              "amount_min": 2000000.0,
              "amount_max": 2000000.0,
              "label": "Exablate Neuro equipment (around $2 million); USD: MedCity News is published by Breaking Media, Inc. of New York, United States"
            },
            "node": "01a101c6-910d-7353-a6a4-2477247204e1",
            "sources": [
              {
                "node": "01a0d908-610f-7f52-8318-e899717726db",
                "kind": "url",
                "id": "https://medcitynews.com/2019/07/insightec-wants-to-usher-in-a-new-era-of-incisionless-surgery/",
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                "id": "https://medcitynews.com/privacy-policy/",
                "url": "https://medcitynews.com/privacy-policy/"
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            ]
          }
        ]
      },
      "theoretical": {
        "description": {
          "state": "known",
          "value": {
            "text": "An ideal half-wavelength focus gives about 0.75 mm at 1 MHz and 1.5 mm at 0.5 MHz, assuming waves converge from all directions. Strong skull scattering above 1 MHz limits this frequency-based estimate, which is not a measured through-skull focus. A cylindrical steering envelope of radius 40 mm and height 80 mm has volume about 4.02 × 10⁻⁴ m³; its boundary is where pressure falls to 50% of the geometric-focus peak."
          },
          "node": "01a15f41-0e46-7b80-aa6b-5de9ea48d02e",
          "sources": [
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              "node": "01a054a3-ed2f-7e23-86bd-e20499df37a0",
              "kind": "doi",
              "id": "10.1016/j.ultrasmedbio.2018.12.015",
              "url": "https://doi.org/10.1016/j.ultrasmedbio.2018.12.015"
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              "node": "01a0abc1-030f-72c1-a31c-eefd53414816",
              "kind": "doi",
              "id": "10.1088/0031-9155/61/24/8476",
              "url": "https://doi.org/10.1088/0031-9155/61/24/8476"
            },
            {
              "node": "01a0e889-f42b-7d51-a9c2-d128cd9c7cc7",
              "kind": "doi",
              "id": "10.1016/j.ultras.2025.107564",
              "url": "https://doi.org/10.1016/j.ultras.2025.107564"
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          ]
        },
        "spatial_resolution_m": {
          "state": "known",
          "value": {
            "min": 0.00075,
            "max": 0.0015,
            "unit": "m",
            "note": "In-principle ideal half-wavelength focal size for transcranial focused ultrasound. Arithmetic: wavelength ≈ 3 mm at 0.5 MHz, so λ/2 ≈ 1.5 mm = 0.0015 m. Assuming wavelength scales as 1/frequency (constant sound speed), λ ≈ 1.5 mm at 1 MHz, so λ/2 ≈ 0.75 mm = 0.00075 m. 1 MHz is the practical upper bound because the skull scatters strongly above 1 MHz. Caveats: this is an idealized bound that assumes waves converge from all directions; the 3 mm wavelength is approximate; practical resolution is only 'on the order of' the wavelength.",
            "operating_points": [
              {
                "label": "1 MHz",
                "min": 0.00075,
                "max": 0.00075,
                "note": "λ ≈ 3 mm × (0.5/1) = 1.5 mm; λ/2 ≈ 0.75 mm. This is the finest case, since the skull scatters strongly above 1 MHz."
              },
              {
                "label": "0.5 MHz",
                "min": 0.0015,
                "max": 0.0015,
                "note": "λ ≈ 3 mm; λ/2 ≈ 1.5 mm."
              }
            ]
          },
          "node": "01a0e88b-a3c2-7fb0-8876-ef214dc5e534",
          "sources": [
            {
              "node": "01a054a3-ed2f-7e23-86bd-e20499df37a0",
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              "id": "10.1016/j.ultrasmedbio.2018.12.015",
              "url": "https://doi.org/10.1016/j.ultrasmedbio.2018.12.015"
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              "node": "01a0e889-f42b-7d51-a9c2-d128cd9c7cc7",
              "kind": "doi",
              "id": "10.1016/j.ultras.2025.107564",
              "url": "https://doi.org/10.1016/j.ultras.2025.107564"
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          ]
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          "state": "incomplete"
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        "field_of_view_m3": {
          "state": "known",
          "value": {
            "min": 0.0004021238596594935,
            "max": 0.0004021238596594935,
            "unit": "m3",
            "note": "Approximate cylindrical steering volume: πr²h = π(0.040 m)²(0.080 m) = 4.0212386×10⁻⁴ m³. The effective steering range is bounded from the geometric focus to where pressure falls to 50% of peak. This is the region over which the beam focus can be steered, not the volume of one focal spot.",
            "endpoint": "reachable_envelope"
          },
          "node": "01a15116-fb21-7283-9eda-72b0bd7496ff",
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        "field_of_view_neurons": {
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    },
    {
      "slug": "histology-ihc",
      "name": "Histology & IHC",
      "group": {
        "id": "microscopy-exvivo",
        "name": "Microscopy & ex vivo"
      },
      "mode": "read",
      "core": false,
      "summary": null,
      "row_node": null,
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        "state": "incomplete"
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        "state": "incomplete"
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        "state": "incomplete"
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        "state": "incomplete"
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        "state": "incomplete"
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          "state": "incomplete"
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    {
      "slug": "icms",
      "name": "ICMS",
      "group": {
        "id": "stim-implanted",
        "name": "Implanted & surgical write"
      },
      "mode": "write",
      "core": true,
      "summary": {
        "value": "Intracortical microstimulation (ICMS) is the writing of small charge-balanced, current-controlled electrical pulses into brain tissue through microelectrode arrays implanted in the cortex. ICMS itself measures nothing; the outcome assessed is the evoked percept. In somatosensory cortex this is an artificial touch whose location follows the electrode and whose intensity follows pulse frequency and amplitude, and such stimulation can partially restore tactile feedback from brain-controlled bionic hands. In a visual-prosthesis feasibility study, arrays in visual cortex evoked phosphenes in a blind participant.",
        "node": "01a150ef-6d43-7660-91c2-778492a2cc7d",
        "sources": [
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            "node": "01a05917-7530-7b63-a43c-162182b5a724",
            "kind": "doi",
            "id": "10.7554/elife.32904",
            "url": "https://doi.org/10.7554/elife.32904"
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            "node": "01a05917-cb68-7ad0-9aab-66c69f9cc25e",
            "kind": "doi",
            "id": "10.1038/s41551-024-01299-z",
            "url": "https://doi.org/10.1038/s41551-024-01299-z"
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            "node": "01a0591b-6f81-7640-ad02-a33c6c214a16",
            "kind": "doi",
            "id": "10.1088/1741-2552/ac18ad",
            "url": "https://doi.org/10.1088/1741-2552/ac18ad"
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            "node": "01a0e5d7-1637-7323-bba4-510f31cc6049",
            "kind": "doi",
            "id": "10.21203/rs.3.rs-8355958/v1",
            "url": "https://doi.org/10.21203/rs.3.rs-8355958/v1"
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      "row_node": "01a16d7d-52e1-7143-ae49-8a35a950a1a9",
      "description": {
        "state": "known",
        "value": {
          "text": "Intracortical microstimulation (ICMS) is the delivery of small current-controlled, charge-balanced pulses into the cortex through implanted microelectrode arrays. In primary somatosensory cortex it evokes discriminable artificial tactile sensations and can partially restore tactile feedback from brain-controlled bionic hands. The percept's location depends on the electrode's location, and its intensity on the pulse frequency and amplitude. Overlapping projected fields from several electrodes produce more localizable and intense sensations. In a feasibility study of a visual prosthesis, untethered wireless floating microelectrode arrays (25 arrays with 400 electrodes, or 32 arrays with 512 electrodes) in dorsolateral visual cortex evoked phosphenes; electrodes with measurable single-electrode thresholds needed about 4 to 59 µA, and a blind participant distinguished gratings as fine as 2.4 cycles per degree."
        },
        "node": "01a150ed-b97f-7d10-9125-0dc2b780a092",
        "sources": [
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            "node": "01a05917-7530-7b63-a43c-162182b5a724",
            "kind": "doi",
            "id": "10.7554/elife.32904",
            "url": "https://doi.org/10.7554/elife.32904"
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          {
            "node": "01a05917-cb68-7ad0-9aab-66c69f9cc25e",
            "kind": "doi",
            "id": "10.1038/s41551-024-01299-z",
            "url": "https://doi.org/10.1038/s41551-024-01299-z"
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            "kind": "doi",
            "id": "10.1088/1741-2552/ac18ad",
            "url": "https://doi.org/10.1088/1741-2552/ac18ad"
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            "node": "01a0e5d7-1637-7323-bba4-510f31cc6049",
            "kind": "doi",
            "id": "10.21203/rs.3.rs-8355958/v1",
            "url": "https://doi.org/10.21203/rs.3.rs-8355958/v1"
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        ]
      },
      "spatial_resolution_m": {
        "state": "known",
        "value": {
          "min": 0.0002,
          "max": 0.0009,
          "unit": "m",
          "note": "Diameter 2r of the region of activated cells around one intracortical microelectrode, from classic current-distance estimates (reported) that 10 microamp and 100 microamp currents activate cells within radii of 100 and 450 micrometres. Human somatosensory-cortex microstimulation through implanted Utah-type arrays uses amplitudes of 2-100 microamps, so these estimates fall in the current range in use; no radius is given for 2 microamps. The arrays' 400 micrometre interelectrode spacing is the sampling grid, not the activated extent.",
          "endpoint": "suprathreshold_extent",
          "operating_points": [
            {
              "label": "10 microamps (reported estimate)",
              "min": 0.0002,
              "max": 0.0002,
              "note": "Radius 100 micrometres, diameter 0.2 mm.",
              "endpoint": "suprathreshold_extent"
            },
            {
              "label": "100 microamps (reported estimate), top of the human S1 amplitude range",
              "min": 0.0009,
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              "note": "Radius 450 micrometres, diameter 0.9 mm.",
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          "note": "Interval between successive stimulation pulses, the reciprocal of pulse frequency, in human somatosensory-cortex microstimulation through two implanted microelectrode arrays with pulses delivered at 20-300 Hz and 2-100 microamps. 300 Hz (3.33 ms) is the maximum of this protocol's frequency range, not a stated stimulator limit. The cathodal phase lasted 200 microseconds and the anodal phase 400 microseconds.",
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          "value": {
            "text": "Spatial selectivity is fine but distributed: in two-photon calcium imaging of layer 2/3 visual cortex in anesthetized rodents and cats, a 15-μm tip displacement activates a distinct near-threshold population, while 30 μm at low current nearly eliminates overlap, implying direct excitation within a 15-μm radius. The current-growing-sphere estimate—100-μm radius at 10 μA and 450 μm at 100 μA—contrasts with sparse cells hundreds of microns away even near threshold (4–9 μA); increasing current fills in a sphere rather than extending its reach. The macroelectrode boundary log(D)=k−log(Q), usually k=1.5–2.0 and fitted to platinum discs on the pial surface, does not transfer directly to microelectrodes, whose damage threshold emerges near 4 nC/phase. In patients, DBS-evoked local responses, which most likely reflect direct nonsynaptic activation of local neuronal elements, have mean absolute and full-recovery refractory periods of 0.56±0.08 ms and 2.94±1.05 ms. Fast corticospinal axons have mean absolute periods of 0.82 ms at high and 1.47 ms at moderate intensity, with complete recovery by 4 ms."
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              "id": "10.1016/s1388-2457(01)00461-8",
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          "value": {
            "min": 0.00056,
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            "unit": "s",
            "note": "Refractory intervals for DBS-evoked local responses and corticospinal D-wave axons in human patients, from the DBS absolute refractory period to complete D-wave recovery. The DBS local response most likely represents nonsynaptic, direct activation of local neuronal elements.",
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            "operating_points": [
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                "label": "Neural absolute refractory period (measured in DBS-evoked responses)",
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              {
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                "note": "Mean 0.00294 s (SD 0.00105 s); 17 human patients; intraoperative DBS recording at subthalamic, pallidal and thalamic targets. Defined as the first interstimulus interval among three consecutive paired-pulse ratios >0.98.",
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              {
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                "min": 0.004,
                "max": 0.004,
                "note": "0.004 s; human patients at anesthetic depths suppressing indirect activity; epidural D-wave recording with two equal transcranial electrical stimuli. Both D2 amplitude and conduction time recovered completely.",
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      "summary": {
        "value": "Intracortical microelectrode arrays are tiny penetrating electrodes implanted into the cortex, the brain's outer layer, on a small silicon array or on flexible threads. They record the electrical spikes of single neurons and of small groups of neurons, plus nearby local field potentials. The same contacts can also deliver microamp-level electrical stimulation.",
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            "url": "https://doi.org/10.3389/fnhum.2026.1777024"
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            "kind": "doi",
            "id": "10.1016/j.neuron.2015.03.037",
            "url": "https://doi.org/10.1016/j.neuron.2015.03.037"
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      "row_node": "01a16cce-a37e-7581-aded-ed6f44bc04cb",
      "description": {
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        "value": {
          "text": "Intracortical microelectrode arrays are penetrating electrodes implanted into the cortex to record the extracellular electrical activity of nearby neurons. They capture the action potentials, or spikes, of single neurons and of small groups of neurons, and nearby local field potentials, at single-neuron and single-spike resolution; the same contacts can deliver microamp-level stimulation current. Noninvasive signals average millions of neurons through the skull, and surface electrodes average thousands and cannot reach deep brain; penetrating arrays resolve individual cells. A 96-channel silicon array is 4 by 4 mm with 1.0 to 1.5 mm shafts at 400 µm pitch; 32-contact probes on flexible threads space their contacts 50 or 75 µm apart. Silicon arrays implanted in the hand and arm areas of motor cortex have let people with severe motor impairment control cursors, orthoses and robotic arms for reaching, grasping and drinking. Flexible-thread systems put up to 3,072 electrodes on 96 leads, inserted robotically with micron precision; a 1,024-electrode device on 64 flexible leads sits flush with the skull. Human use has involved surgical cortical implantation with a pneumatic impulse inserter, wiring to a skull-fixed percutaneous pedestal, aseptic cable connection each session and, in one case, 2 days of ICU monitoring. In a 2015 review of mesoscopic neurotechnologies, penetrating arrays in humans covered a relatively small cortical area, about 1 cm², and larger coverage was limited by the risk of tissue damage."
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          "note": "The 50 μm localization figure comes from a tetrode gradually stepped through cortex, not a fixed implanted array. Tetrodes (Thomas Recording) of the kind many laboratories use for cortical single units, in visual cortex of one cat (area 17) and two monkeys (V1, V4): when the tetrode is gradually stepped through cortex, a single neuron's location can be determined to within a sphere of radius about 50 um. The recording radius, the distance from the tip enclosing half of the 61 isolated neurons, is about 100 um (about 130 um for the 95th percentile); it measures how far from the tip neurons are isolated, not how closely two neurons can be separated. The isolated fraction of all neurons within the recording volume is about 1% or smaller.",
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              "label": "Median recording radius (half of isolated neurons)",
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              "note": "R50 about 97-100 um from the tetrode tip; reach, not separation.",
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              "note": "95% of isolated neurons lie within about 130 um of the tip; reach, not separation.",
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            "id": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3154810/",
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      "temporal_resolution_s": {
        "state": "known",
        "value": {
          "min": 0.0002,
          "max": 0.0002,
          "unit": "s",
          "note": "Reciprocal upper filter cutoff: the reported spike band is filtered at 250–5000 Hz, and 1/5000 Hz = 0.2 ms. This is a stipulated bandwidth-derived proxy, not a measured finest distinguishable neural-event time difference. Acquisition sampling is 19.3–30 kHz (intervals about 33–52 µs), a separate hardware quantity. The 20- or 100-ms bins used to process 30-kHz data are decoding choices; no separate decoder update interval is stated."
        },
        "node": "01a16655-e70b-7301-85a7-a479533b6499",
        "sources": [
          {
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            "id": "10.1038/nature11076",
            "url": "https://doi.org/10.1038/nature11076"
          },
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            "kind": "doi",
            "id": "10.1088/1741-2552/ac127e",
            "url": "https://doi.org/10.1088/1741-2552/ac127e"
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          {
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            "kind": "doi",
            "id": "10.2196/16194",
            "url": "https://doi.org/10.2196/16194"
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          {
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            "kind": "doi",
            "id": "10.3389/fnhum.2026.1777024",
            "url": "https://doi.org/10.3389/fnhum.2026.1777024"
          }
        ]
      },
      "field_of_view_m3": {
        "state": "known",
        "value": {
          "min": 2.4576e-7,
          "max": 2.4576e-7,
          "unit": "m3",
          "note": "Largest implant described: 16 Utah arrays (8 × 8 electrodes each, 1,024 electrodes per subject) in V1 and V4 of two macaques, with 1.5 mm shanks at 400 µm inter-shank spacing. Stipulating each array's footprint as a 3.2 × 3.2 mm square (eight pitches) and its depth as the 1.5 mm shank length gives 15.36 mm³ per array and 245.76 mm³ (2.4576 × 10⁻⁷ m³) for 16 arrays, counting only tissue under the arrays. The glued implant spanned about 3 cm of cortex, but that span is not filled with electrodes.",
          "endpoint": "sensing_envelope",
          "operating_points": [
            {
              "label": "16 Utah arrays, macaque V1 and V4",
              "min": 2.4576e-7,
              "max": 2.4576e-7,
              "note": "16 × 3.2 mm × 3.2 mm × 1.5 mm (stipulated footprint).",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "Single 96-channel array, motor cortex",
              "min": 2.4e-8,
              "max": 2.4e-8,
              "note": "4 × 4 mm footprint (16 mm²) × 1.5 mm electrode length = 24 mm³.",
              "endpoint": "sensing_envelope"
            }
          ]
        },
        "node": "01a15cdc-6ad8-7573-b871-5f1f458a40fb",
        "sources": [
          {
            "node": "01a05495-a390-77c2-ba76-338da68c88a8",
            "kind": "doi",
            "id": "10.1038/nature11076",
            "url": "https://doi.org/10.1038/nature11076"
          },
          {
            "node": "01a0dbae-2bfc-77c3-acf6-23388fc9e473",
            "kind": "doi",
            "id": "10.1088/1741-2552/ace07e",
            "url": "https://doi.org/10.1088/1741-2552/ace07e"
          }
        ]
      },
      "field_of_view_neurons": {
        "state": "known",
        "value": {
          "min": 1026.0,
          "max": 1026.0,
          "unit": "neuron",
          "note": "Largest single-session count of manually sorted neurons: eight Utah arrays (768 electrodes), four in each lateral prefrontal cortex, in macaques. Over four sessions per monkey, 877, 942, 1026 and 598 neurons were recorded in monkey V and 680, 747, 677 and 585 in monkey W.",
          "endpoint": "sensing_envelope",
          "operating_points": [
            {
              "label": "Eight Utah arrays, macaque lateral prefrontal cortex, per session",
              "min": 585.0,
              "max": 1026.0,
              "note": "Range over eight sessions in two monkeys.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "One 96-channel array (NWB session)",
              "min": 74.0,
              "max": 74.0,
              "note": "74 sorted units in one session from a single 96-channel array.",
              "endpoint": "sensing_envelope"
            }
          ]
        },
        "node": "01a16a2a-008e-77d1-8c06-2d7ad27d6b19",
        "sources": [
          {
            "node": "01a05495-a390-77c2-ba76-338da68c88a8",
            "kind": "doi",
            "id": "10.1038/nature11076",
            "url": "https://doi.org/10.1038/nature11076"
          },
          {
            "node": "01a06f26-898e-7d80-bcf2-7297368f14a8",
            "kind": "url",
            "id": "https://api.dandiarchive.org/api/assets/8b2379dc-338b-4997-abc7-78f2eb4ccb6c/download/",
            "url": "https://api.dandiarchive.org/api/assets/8b2379dc-338b-4997-abc7-78f2eb4ccb6c/download/"
          },
          {
            "node": "01a15ceb-2d45-7f10-9fb4-89809441ab55",
            "kind": "doi",
            "id": "10.1038/s41467-021-20943-9",
            "url": "https://doi.org/10.1038/s41467-021-20943-9"
          }
        ]
      },
      "measurand": {
        "state": "known",
        "value": {
          "measurands": [
            "extracellular action potentials (single- and multi-unit spikes)",
            "local field potentials"
          ],
          "note": "The same electrode contacts can also deliver microamp-level stimulation currents."
        },
        "node": "01a0ab7b-7559-7e53-aee1-d5430dcff127",
        "sources": [
          {
            "node": "01a05495-a390-77c2-ba76-338da68c88a8",
            "kind": "doi",
            "id": "10.1038/nature11076",
            "url": "https://doi.org/10.1038/nature11076"
          },
          {
            "node": "01a05495-af30-70e1-a4f0-c308bed8bfec",
            "kind": "doi",
            "id": "10.1088/1741-2552/ac127e",
            "url": "https://doi.org/10.1088/1741-2552/ac127e"
          },
          {
            "node": "01a05495-babd-7940-b659-8e2a05eba5de",
            "kind": "doi",
            "id": "10.2196/16194",
            "url": "https://doi.org/10.2196/16194"
          },
          {
            "node": "01a05495-c139-7530-986f-6cb5ab678aaf",
            "kind": "doi",
            "id": "10.3389/fnhum.2026.1777024",
            "url": "https://doi.org/10.3389/fnhum.2026.1777024"
          }
        ]
      },
      "stimulation": {
        "state": "incomplete"
      },
      "destructiveness": {
        "state": "known",
        "value": {
          "kind": "minimally_destructive",
          "note": "Intracortical arrays cause localized, mm²-scale incidental injury (fibrosis, gliosis/inflammation, foreign-body reaction, microhemorrhage, neuronal loss, white-matter necrosis). 14 patients, 12,203 days: 68 device-related events, mostly skin irritation; clinically significant events not separately counted. Scaling to many arrays is limited by risk of significant cumulative tissue damage, especially in intact critical cortex."
        },
        "node": "01a0febe-aaba-7882-8d4a-b210e700de6c",
        "sources": [
          {
            "node": "01a05495-af30-70e1-a4f0-c308bed8bfec",
            "kind": "doi",
            "id": "10.1088/1741-2552/ac127e",
            "url": "https://doi.org/10.1088/1741-2552/ac127e"
          },
          {
            "node": "01a05495-babd-7940-b659-8e2a05eba5de",
            "kind": "doi",
            "id": "10.2196/16194",
            "url": "https://doi.org/10.2196/16194"
          },
          {
            "node": "01a05495-c139-7530-986f-6cb5ab678aaf",
            "kind": "doi",
            "id": "10.3389/fnhum.2026.1777024",
            "url": "https://doi.org/10.3389/fnhum.2026.1777024"
          },
          {
            "node": "01a054ac-ee51-7d02-8b42-5d19746edceb",
            "kind": "doi",
            "id": "10.1016/j.neuron.2015.03.037",
            "url": "https://doi.org/10.1016/j.neuron.2015.03.037"
          }
        ]
      },
      "preparation": {
        "state": "known",
        "value": {
          "steps": [
            {
              "kind": "surgery",
              "note": "Humans: cortical arrays were implanted with a pneumatic impulse inserter and wired to a skull-fixed percutaneous pedestal; cables were connected aseptically each session, and one case had 2 days of ICU monitoring."
            },
            {
              "kind": "surgery",
              "note": "Rhesus macaques: craniotomy and closure methods varied; arrays were inserted orthogonally with a micromanipulator-held pneumatic inserter at ~172 kPa, with excursion matched to the 0.5–1.5 mm array length."
            }
          ],
          "note": "Human and macaque procedures are separately reported."
        },
        "node": "01a0b22c-81da-7e13-a8ba-66fdaaf2ad3a",
        "sources": [
          {
            "node": "01a05495-a390-77c2-ba76-338da68c88a8",
            "kind": "doi",
            "id": "10.1038/nature11076",
            "url": "https://doi.org/10.1038/nature11076"
          },
          {
            "node": "01a05495-af30-70e1-a4f0-c308bed8bfec",
            "kind": "doi",
            "id": "10.1088/1741-2552/ac127e",
            "url": "https://doi.org/10.1088/1741-2552/ac127e"
          },
          {
            "node": "01a05495-babd-7940-b659-8e2a05eba5de",
            "kind": "doi",
            "id": "10.2196/16194",
            "url": "https://doi.org/10.2196/16194"
          },
          {
            "node": "01a05944-8680-7952-91c1-e99d6166de57",
            "kind": "doi",
            "id": "10.1088/1741-2560/10/6/066014",
            "url": "https://doi.org/10.1088/1741-2560/10/6/066014"
          }
        ]
      },
      "cost": {
        "state": "known",
        "items": [
          {
            "value": {
              "kind": "procedure",
              "amount_min": 30000.0,
              "amount_max": 100000.0,
              "label": "Surgical procedure for an invasive BCI, review estimate stated as $30,000-$100,000 (currency symbol $ as given); electrodes, device maintenance and support add further cost"
            },
            "node": "01a15d07-5886-77e3-bf00-8dfad8b08cff",
            "sources": [
              {
                "node": "01a05495-c139-7530-986f-6cb5ab678aaf",
                "kind": "doi",
                "id": "10.3389/fnhum.2026.1777024",
                "url": "https://doi.org/10.3389/fnhum.2026.1777024"
              }
            ]
          }
        ]
      },
      "theoretical": {
        "description": {
          "state": "known",
          "value": {
            "text": "Spatially, dense recording sites set the in-principle limit for locating a spike source. A Monte Carlo model of a 1/R point source 15 µm from the probe, with 50 µV peak amplitude and 14 µV rms noise, gives a position-estimate standard deviation of about 5 µm for a layout of 5×5 µm sites at 6 µm pitch (NP Ultra) and about 25 µm for the coarser NP 2.0 layout. This is a model value, described as the upper limit of position resolution; experimental scatter can be larger.\n\nTemporally, in 11 somatic paired recordings in hippocampus in vivo with wideband (1 Hz-3 kHz) filtering, the cell-to-cell standard deviation of the offset between extracellular and intracellular waveform landmarks ranged from 0.02 ms at spike onset to 0.14 ms at spike end. These are offsets between averaged waveforms, not spike-by-spike jitter. The extracellular negative peak leads the intracellular peak by 0.20 ms, and durations agree (1.28 vs 1.27 ms). Higher-frequency filtering changes these relationships.\n\nCoverage has only an idealized envelope: penetrating shanks of 1.5 mm tiling the exposed pial surface of both hemispheres (twice one measured hemisphere's 42,619 mm²) would reach about 1.28 × 10⁻⁴ m³. Cortex folded inside sulci lies outside this envelope, and it is not a demonstrated implant."
          },
          "node": "01a15ce6-84d2-7151-b5aa-735feb01d04d",
          "sources": [
            {
              "node": "01a0c15a-64c1-74c2-b59e-5cb7fc87eeab",
              "kind": "doi",
              "id": "10.3389/fnana.2013.00028",
              "url": "https://doi.org/10.3389/fnana.2013.00028"
            },
            {
              "node": "01a0d352-3b18-7e62-aeb4-63746ea1a9de",
              "kind": "doi",
              "id": "10.1152/jn.2000.84.1.390",
              "url": "https://doi.org/10.1152/jn.2000.84.1.390"
            },
            {
              "node": "01a0dbae-2bfc-77c3-acf6-23388fc9e473",
              "kind": "doi",
              "id": "10.1088/1741-2552/ace07e",
              "url": "https://doi.org/10.1088/1741-2552/ace07e"
            },
            {
              "node": "01a0e901-8146-7fd0-901e-8abbbaf58ac7",
              "kind": "doi",
              "id": "10.1016/j.neuron.2025.08.030",
              "url": "https://doi.org/10.1016/j.neuron.2025.08.030"
            }
          ]
        },
        "spatial_resolution_m": {
          "state": "known",
          "value": {
            "max": 5e-6,
            "unit": "m",
            "note": "Best-case modeled spike-source position resolution for Neuropixels-class probes: about 5 µm (standard deviation of the position estimate) for the NP Ultra pattern (5×5 µm sites, 6 µm pitch). The figure comes from a Monte Carlo model of a 1/R point source placed 15 µm from the probe, with 50 µV peak amplitude and 14 µV rms noise. It is a model value, not an experimental measurement, and is described as the upper limit of position resolution; experimental position scatter can be larger. Denser sampling improves it because more sites fall within the 60 µm fit radius, which reduces the impact of noise. By contrast, the coarser NP 2.0 pattern gives about 25 µm under the same model.",
            "endpoint": "localisation_error",
            "operating_points": [
              {
                "label": "Model-based, NP Ultra pattern (5×5 µm sites, 6 µm pitch); point source at 15 µm, 50 µV peak, 14 µV rms noise",
                "max": 5e-6,
                "note": "Monte Carlo standard deviation of the position estimate. It is a best-case figure, and experimental scatter can be larger. The coarser NP 2.0 pattern gives about 25 µm under the same conditions.",
                "endpoint": "localisation_error"
              }
            ]
          },
          "node": "01a15142-da71-7763-be5c-c6342ee2fa09",
          "sources": [
            {
              "node": "01a0e901-8146-7fd0-901e-8abbbaf58ac7",
              "kind": "doi",
              "id": "10.1016/j.neuron.2025.08.030",
              "url": "https://doi.org/10.1016/j.neuron.2025.08.030"
            }
          ]
        },
        "temporal_resolution_s": {
          "state": "incomplete"
        },
        "field_of_view_m3": {
          "state": "known",
          "value": {
            "min": 0.000127857,
            "max": 0.000127857,
            "unit": "m3",
            "note": "Idealized area × depth envelope, not a demonstrated implant: the cortical layer reachable by penetrating shanks if arrays tiled the exposed (non-sulcal) pial surface of both hemispheres. One measured human hemisphere has an exposed pial surface of 42,619 mm²; stipulating the same for the other hemisphere gives 85,238 mm². Multiplying by the 1.5 mm shank length of the cited 16-array macaque implant gives 127,857 mm³ (1.27857 × 10⁻⁴ m³). Folded cortex inside sulci (total grey-matter pial surface 94,050 mm² per hemisphere) lies outside this envelope.",
            "endpoint": "reachable_envelope"
          },
          "node": "01a15cff-c807-7d01-acaf-f4a3ba22eede",
          "sources": [
            {
              "node": "01a0c15a-64c1-74c2-b59e-5cb7fc87eeab",
              "kind": "doi",
              "id": "10.3389/fnana.2013.00028",
              "url": "https://doi.org/10.3389/fnana.2013.00028"
            },
            {
              "node": "01a0dbae-2bfc-77c3-acf6-23388fc9e473",
              "kind": "doi",
              "id": "10.1088/1741-2552/ace07e",
              "url": "https://doi.org/10.1088/1741-2552/ace07e"
            }
          ]
        },
        "field_of_view_neurons": {
          "state": "incomplete"
        }
      }
    },
    {
      "slug": "intraoperative-flow-cytometry",
      "name": "Intraoperative flow cytometry",
      "group": {
        "id": "microscopy-exvivo",
        "name": "Microscopy & ex vivo"
      },
      "mode": "read",
      "core": false,
      "summary": null,
      "row_node": "01a16cad-81b5-79e1-a3f4-10c1ae6efee1",
      "description": {
        "state": "incomplete"
      },
      "spatial_resolution_m": {
        "state": "incomplete"
      },
      "temporal_resolution_s": {
        "state": "known",
        "value": {
          "min": 540.0,
          "max": 600.0,
          "unit": "s",
          "note": "One glioma-biopsy specimen to one completed flow-cytometry result took 9–10 minutes in the clinical study (540–600 s; mean 570 s). The result is a specimen-level malignancy index. This time per completed static measurement does not describe individual-cell passage intervals or the spacing of independently scheduled biopsies.",
          "endpoint": "sample_interval"
        },
        "node": "01a16c9d-4572-7152-b189-41054bf995c9",
        "sources": [
          {
            "node": "01a165f5-5748-77c1-9f19-4be7d393432b",
            "kind": "agent_knowledge",
            "id": "agent: gpt-6 c2c08e7bb5eb",
            "url": null
          },
          {
            "node": "01a16c98-5a31-77f1-9400-fa3c98de0fd0",
            "kind": "doi",
            "id": "10.3171/2013.1.JNS12681",
            "url": "https://doi.org/10.3171/2013.1.JNS12681"
          }
        ]
      },
      "field_of_view_m3": {
        "state": "incomplete"
      },
      "field_of_view_neurons": {
        "state": "incomplete"
      },
      "measurand": {
        "state": "incomplete"
      },
      "stimulation": {
        "state": "incomplete"
      },
      "destructiveness": {
        "state": "incomplete"
      },
      "preparation": {
        "state": "incomplete"
      },
      "cost": {
        "state": "incomplete"
      },
      "theoretical": {
        "description": {
          "state": "incomplete"
        },
        "spatial_resolution_m": {
          "state": "incomplete"
        },
        "temporal_resolution_s": {
          "state": "incomplete"
        },
        "field_of_view_m3": {
          "state": "incomplete"
        },
        "field_of_view_neurons": {
          "state": "incomplete"
        }
      }
    },
    {
      "slug": "intraoperative-mri",
      "name": "Intraoperative MRI",
      "group": {
        "id": "mri",
        "name": "MRI"
      },
      "mode": "read",
      "core": false,
      "summary": null,
      "row_node": null,
      "description": {
        "state": "incomplete"
      },
      "spatial_resolution_m": {
        "state": "incomplete"
      },
      "temporal_resolution_s": {
        "state": "incomplete"
      },
      "field_of_view_m3": {
        "state": "incomplete"
      },
      "field_of_view_neurons": {
        "state": "incomplete"
      },
      "measurand": {
        "state": "incomplete"
      },
      "stimulation": {
        "state": "incomplete"
      },
      "destructiveness": {
        "state": "incomplete"
      },
      "preparation": {
        "state": "incomplete"
      },
      "cost": {
        "state": "incomplete"
      },
      "theoretical": {
        "description": {
          "state": "incomplete"
        },
        "spatial_resolution_m": {
          "state": "incomplete"
        },
        "temporal_resolution_s": {
          "state": "incomplete"
        },
        "field_of_view_m3": {
          "state": "incomplete"
        },
        "field_of_view_neurons": {
          "state": "incomplete"
        }
      }
    },
    {
      "slug": "intraoperative-radiotherapy",
      "name": "Intraoperative radiotherapy",
      "group": {
        "id": "stim-implanted",
        "name": "Implanted & surgical write"
      },
      "mode": "write",
      "core": false,
      "summary": null,
      "row_node": null,
      "description": {
        "state": "incomplete"
      },
      "spatial_resolution_m": {
        "state": "incomplete"
      },
      "temporal_resolution_s": {
        "state": "incomplete"
      },
      "field_of_view_m3": {
        "state": "incomplete"
      },
      "field_of_view_neurons": {
        "state": "incomplete"
      },
      "measurand": {
        "state": "incomplete"
      },
      "stimulation": {
        "state": "incomplete"
      },
      "destructiveness": {
        "state": "incomplete"
      },
      "preparation": {
        "state": "incomplete"
      },
      "cost": {
        "state": "incomplete"
      },
      "theoretical": {
        "description": {
          "state": "incomplete"
        },
        "spatial_resolution_m": {
          "state": "incomplete"
        },
        "temporal_resolution_s": {
          "state": "incomplete"
        },
        "field_of_view_m3": {
          "state": "incomplete"
        },
        "field_of_view_neurons": {
          "state": "incomplete"
        }
      }
    },
    {
      "slug": "intraoperative-ultrasound",
      "name": "Structural ultrasound (intraoperative)",
      "group": {
        "id": "optical",
        "name": "Optical & ultrasound (in vivo)"
      },
      "mode": "read",
      "core": false,
      "summary": null,
      "row_node": null,
      "description": {
        "state": "incomplete"
      },
      "spatial_resolution_m": {
        "state": "incomplete"
      },
      "temporal_resolution_s": {
        "state": "incomplete"
      },
      "field_of_view_m3": {
        "state": "incomplete"
      },
      "field_of_view_neurons": {
        "state": "incomplete"
      },
      "measurand": {
        "state": "incomplete"
      },
      "stimulation": {
        "state": "incomplete"
      },
      "destructiveness": {
        "state": "incomplete"
      },
      "preparation": {
        "state": "incomplete"
      },
      "cost": {
        "state": "incomplete"
      },
      "theoretical": {
        "description": {
          "state": "incomplete"
        },
        "spatial_resolution_m": {
          "state": "incomplete"
        },
        "temporal_resolution_s": {
          "state": "incomplete"
        },
        "field_of_view_m3": {
          "state": "incomplete"
        },
        "field_of_view_neurons": {
          "state": "incomplete"
        }
      }
    },
    {
      "slug": "isoi",
      "name": "Intrinsic optical signal imaging",
      "group": {
        "id": "optical",
        "name": "Optical & ultrasound (in vivo)"
      },
      "mode": "read",
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          "text": "Laser interstitial thermal therapy (LITT) is MRI-guided thermal ablation of a target tissue with laser heat, delivered through a laser fiber placed in the brain along a stereotactic path. The procedure uses preprocedural stereotactic MRI, general anaesthesia, MRI-compatible head fixation and navigation, and a burr hole with a stereotactic bolt through which the probe is placed. The laser is then activated while real-time MRI monitoring maps the temperature around the fiber as thermal isodose lines. Two commercial platforms differ in their delivery: Visualase delivers continuous 980 nm laser energy through a saline-cooled diffusing fiber, and NeuroBlate delivers pulsed 1064 nm energy through a CO2-cooled side-firing or diffusing probe. The temperature reached sets the tissue outcome. Apoptosis begins around 45 °C. Irreversible coagulation occurs from 45 to 90 °C. Necrosis through protein denaturation sets in around 52 °C and extends across 50 to 80 °C. Above 100 °C a cavity forms. Histologically, the heated volume grades outward from central coagulation through edema to normal tissue."
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          "note": "Single-position ablation diameter (5–20 mm). The temperature falls off sharply at the ablation-zone edge; an interface with surrounding tissue >0.001 m is generally considered safe.",
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          "note": "In six awake brain-tumour laser ablations, the mean volume inside the blue thermal-damage threshold was 12.06 cm³ (standard error 2.75 cm³). This software-estimated ablation volume corresponds to thermal exposure equivalent to 43 °C for 10 minutes.",
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          "note": "Continuous or pulsed near-infrared laser energy from a stereotactic fiber heats tissue to temperatures that set the outcome (necrosis near 52C, coagulation 45-90C, cavitation above 100C); delivery is tracked with real-time MRI thermometry."
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          "note": "LITT intentionally causes irreversible tissue necrosis/damage. One report describes central necrosis, peripheral irreversible necrotizing edema, and outer reversible edema/viable cells; a separate human-histology report describes Zone 1 acellular necrosis, Zone 2 macrophage-rich granulation tissue, and Zone 3 viable tumor."
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              "note": "Preprocedural stereotactic MRI and MRI-compatible navigation for targeting, and real-time thermal-isodose MRI monitoring during laser activation."
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            "text": "A diffusing-tip laser fiber emits an ellipsoidal light profile. Carbonization increases absorption and limits light penetration; overheating can vaporize tissue and cause explosive rupture. Stereotactic MR-guided delivery can reach deep brain targets, and can access targets throughout the brain. This whole-brain reach does not mean the entire brain is ablated at once."
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            "note": "Whole brain, recorded as the larger (male) adult mean total brain volume, 1233.58 cm3. MR-guided laser interstitial thermal therapy provides minimally invasive access anywhere in the brain, and deep-seated targets inaccessible to open surgery (thalamus, hypothalamus, mesial basal temporal lobe, brainstem) may be treated. The laser is delivered along stereotactic trajectories, one or two per tumour in one deep-seated glioblastoma series, with consecutive ablations of 5-20 mm diameter made while withdrawing the fiber by 5-10 mm. The largest treated tumour in that series, 91.73 cm3, is a practical treated volume, not this limit.",
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          "note": "The ≤25 ms figure is a reciprocal-bandwidth timing estimate, dt ~ 1/B, using the neural signal captured above noise as the effective bandwidth B. It estimates a timing scale rather than a measured two-event discrimination limit; sampling interval and sensor response bandwidth are separate quantities. With an on-scalp array of alkali OPMs (sensor bandwidth about 130 Hz), visual gamma-band (40-70 Hz) power increases are visible in single-trial responses and are detected at an SNR similar to or better than SQUID MEG. Neural signal at 40 Hz or above is therefore captured, giving a reciprocal-bandwidth timing estimate of 1/40 s (25 ms) or finer. Alkali OPM noise (about 10 fT per root Hz) and limited bandwidth prevent them from measuring the 450-850 Hz somatosensory evoked responses that SQUID MEG resolves. Sensor response bandwidths, a sensor property rather than demonstrated neural timing and describing attenuation (3 dB points and low-pass roll-off) rather than hard cutoffs, are about 120-350 Hz for alkali zero-field sensors and DC to 2 kHz for helium-4 OPMs, for which recording high gamma, ripples and fast ripples is described as a possibility the bandwidth opens.",
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          "note": "OPM-MEG records weak magnetic fields and infers net dendritic postsynaptic currents. Versus fixed adult-sized SQUID helmets, closer on-scalp OPMs yield larger signals despite lower intrinsic sensor sensitivity."
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          "note": "No participant preparation beyond ordinary sensor placement is required. OPM sensors are worn directly on the scalp, rather than in a fixed SQUID helmet. Recording still requires a low-field, magnetically shielded environment, potentially with nulling coils."
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            "text": "Spatially, idealized asymptotic multipolar theory gives MEG no finite resolution floor independent of sensor count. Field smoothing suppresses fine spatial scales without eliminating them, so denser grids improve resolution logarithmically slowly. Magnetically silent sources remain unresolved.\n\nRecoverable timing is taken as dt ≈ 1/B, where B is neural signal frequency captured above noise. Ultralow-noise SQUID MEG provides a separate neural benchmark of about 1–1.3 ms from resting activity near 1 kHz and evoked band edges at 750–850 Hz; this is not demonstrated OPM neural timing. An on-scalp alkali OPM array detected single-trial visual gamma in the 40–70 Hz band, supporting 25 ms or finer using that approximation.\n\nA power-broadened single-beam SERF OPM is reported to reach about 1 kHz sensor bandwidth with a 30 fT/√Hz noise floor, with a sensitivity-bandwidth tradeoff. Its noise is roughly 170 times the 0.18 fT/√Hz of the ultralow-noise SQUID system; this comparison does not establish a detectability threshold. Sensor response bandwidths of about 120–350 Hz for alkali zero-field sensors and DC to 2 kHz for helium-4 OPMs describe attenuation and roll-off rather than hard cutoffs or demonstrated neural timing.\n\nA whole-head OPM coverage analysis found reasonable but nonuniform cortical sensitivity, lowest at the temporal pole and cerebellum. The whole-brain anatomical reference uses the adult male mean of 1233.58 cm³; it is neither a quantified reachable envelope nor an individual bound."
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            "note": "Modelled, not measured: in a two-source beamformer simulation of a 275-channel on-scalp OPM system (orthogonal Gaussian source time courses with SD 5 nAm, sensor noise SD 35 fT, no forward-field error), the minimum separation at which two cortical dipoles become resolvable (reconstructed time-course correlation below 1/√2) averages 2.5 mm over one hemisphere, with mean correlation 0.29 at that separation; the discrete cortical mesh prevents an exact threshold. The same simulation gives 6.3 mm (correlation 0.49) for a 275-channel SQUID system. This is not a hard floor: multipolar analysis finds that adding sensors improves MEG spatial resolution without limit, though only logarithmically slowly, and magnetically silent source configurations stay invisible.",
            "endpoint": "two_source_separation",
            "operating_points": [
              {
                "label": "Simulated 275-channel SQUID system, same analysis",
                "min": 0.0063,
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          "value": {
            "min": 0.001,
            "max": 0.0013,
            "unit": "s",
            "note": "Conditional in-principle estimates taking recoverable timing as dt ≈ 1/B, where B is the highest frequency shown above noise; these are not demonstrated OPM neural timing. Neural regime: ultralow-noise SQUID MEG shows resting-state activity above system noise up to about 1 kHz (~1 ms), and median-nerve-evoked hfSER band edges at 750–850 Hz (~1.2–1.3 ms). Sensor regime: a power-broadened single-beam SERF OPM reaches about 1 kHz bandwidth (~1 ms). Raising bandwidth lowers the achievable sensitivity, so SERF OPMs face a sensitivity-bandwidth tradeoff.",
            "operating_points": [
              {
                "label": "Neural: ultralow-noise SQUID MEG (resting state and evoked hfSER)",
                "min": 0.001,
                "max": 0.0013,
                "note": "About 1 kHz resting-state limit gives ~1/1000 s. The hfSER upper edges of 750 Hz, or 850 Hz in the multichannel system, give 1/850 to 1/750 s. Highest-frequency content is limited by signal amplitude against noise."
              },
              {
                "label": "Sensor: power-broadened single-beam SERF OPM",
                "min": 0.001,
                "max": 0.001,
                "note": "About 1 kHz bandwidth, obtained with power broadening plus light-power stabilization, gives ~1/1000 s. Sensitivity decreases as measurement bandwidth increases."
              }
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          "node": "01a16b68-814b-7820-9fcc-5c82295aeffe",
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        "field_of_view_m3": {
          "state": "known",
          "value": {
            "min": 0.00111576,
            "max": 0.00123358,
            "unit": "m3",
            "note": "Whole brain anatomical reference: adult female and male mean total brain volumes (1115.76 and 1233.58 cm³), not measurements or bounds for any subject or a quantified reachable envelope. The whole-head OPM-MEG coverage analysis found reasonable sensitivity across the entire cortex, with the temporal pole and cerebellum suffering the lowest sensitivity."
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          "node": "01a15183-c6d4-7830-bbc1-3e6eacc47308",
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    {
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      "name": "MEG (SQUID)",
      "group": {
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        "name": "Electrophysiology"
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      "core": true,
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        "value": "SQUID-based (cryogenic) MEG is a helmet of superconducting sensors kept near -270 °C by liquid helium; in 2018 commercial systems held about 300 sensors in such a cooled container. It reads the extremely weak magnetic fields outside the head, about 10⁻¹⁵ to 10⁻¹¹ tesla, produced by neuronal electrical activity, and from them infers the underlying currents, mainly postsynaptic currents in aligned cortical pyramidal cells, so the neural source is estimated indirectly. It is usually paired with MRI.",
        "node": "01a15108-5742-7e91-bacb-0560dbbbe89b",
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      "row_node": "01a16a4b-ac02-7dc0-a295-552717509ff1",
      "description": {
        "state": "known",
        "value": {
          "text": "SQUID-based MEG is the recording of the weak magnetic fields outside the head that are generated by the electrical activity of neurons. The sensor is a superconducting quantum interference device (SQUID): a small superconducting loop interrupted by two weak links, the Josephson junctions. At very low temperature a SQUID is extremely sensitive to changes in magnetic field, of the order of 10⁻¹⁵ T, and its output is converted to a digital signal. Neuromagnetic fields are extremely weak, about 10⁻¹⁵ to 10⁻¹¹ T, and must be detected against environmental magnetic noise from external electrical and magnetic equipment of about 10⁻⁷ T and above. In 2018, commercial systems held about 300 sensors in a cryogenic vessel, the dewar, containing liquid helium; flux transformers couple the neuromagnetic field to the SQUIDs. Liquid helium, near -270 °C, keeps the sensors superconducting. The sensor array is a helmet that gives whole-head coverage. The recorded fields cross the dura, skull and scalp relatively unaltered and carry millisecond-accurate information about neuronal currents. MEG primarily reflects net intracellular dendritic postsynaptic currents in aligned cortical pyramidal cells. It is usually combined with MRI to give magnetic source imaging."
        },
        "node": "01a15107-67b1-70e0-928a-2fe1e967aa2f",
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            "id": "10.1016/j.clinph.2018.03.042",
            "url": "https://doi.org/10.1016/j.clinph.2018.03.042"
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          "note": "Low-field/portable MRI is non-invasive and non-ionizing. This procedure-level classification does not guarantee that ordinary use causes no tissue damage."
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          "note": "No patient prerequisites beyond ordinary participation are specified for the portable low-field systems described."
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          {
            "value": {
              "kind": "build",
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              "label": "Authors' estimate of hardware material costs for a 0.055 T ultra-low-field, shielding-free brain MRI scanner (prototype developed in study), under quantity production: under USD 20K. Build-material estimate only, not the price of a commercially purchased scanner."
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          "value": {
            "text": "At low field, reduced SNR—especially below 0.1 T—limits spatial resolution, while temporal resolution is separately reduced. Spectral fat/water separation is poor; susceptibility artifacts may decrease, but metallic-implant artifacts may persist."
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            "note": "The temporal resolution of MRI is limited by spin relaxation. Fully independent sequential acquisitions need spins to recover equilibrium magnetization on the T1 timescale (100-1000 ms); if local T1 is static and pre-mapped, T2-sensitive effects could be refreshed on the faster T2 timescale (10-100 ms), and events shorter than T1 and T2 may be detectable when the signal change overcomes the dependence between acquisitions. Whole-brain imaging at 100 ms per volume has been realised with an undersampled T2*-weighted spiral sequence (MREG) on 3 T scanners, with nominal 3 mm isotropic voxels.",
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          "text": "Structural MRI uses nuclear magnetic resonance: a static field aligns protons and an RF pulse perturbs them. Precessing transverse magnetization changes magnetic flux, inducing a receiver-coil signal whose timing and amplitude reflect tissue-dependent T1/T2 relaxation, creating contrast in T1w (e.g. MP-RAGE), T2w and T2-FLAIR."
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          "note": "Structural MRI of the living human brain: effective resolution approximately 290 μm in the slice direction, alongside protocol-specific voxel sampling. A 7 T whole-brain T1-weighted acquisition of a single young healthy subject with prospective motion correction had a nominal isotropic resolution of 250 μm. Its 6/8 slice partial Fourier acquisition with zero-filling widens the point-spread FWHM by about 15%, giving an effective ≈290 μm in the L-R slice-encoding direction. ADNI4 specifies nominal 1 mm isotropic voxels for T1 MP-RAGE, 3D T2 and 3D FLAIR, and 0.5 × 0.5 × 1.8 mm³ voxels for 3D T2*. A separate study's anatomical T1 MPRAGE scan used nominal 1 mm isotropic voxels; its subject population is not specified. Without the in vivo time limit, a whole formalin-fixed human brain specimen was imaged ex vivo on a 7 T scanner at 100 um isotropic resolution over about 100 hours.",
          "endpoint": "point_spread",
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              "endpoint": "sampling"
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              "label": "Ex vivo whole fixed human brain, 7 T, ~100 h (nominal)",
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          "note": "One image every 104 s for a complete CS-MP-RAGE volume. The acquisition yields one static structural image volume; MP-RAGE takes 312 s, 3D T2-weighted FLAIR 380 s, and whole-brain SWI at 3 T with parallel imaging as little as 240 s.",
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          "note": "Whole brain. A single structural acquisition with 0.55 mm isotropic sampling (13 min) reached high RF-field homogeneity throughout the whole brain volume. The mP-RAGE, CS-MP-RAGE and 3D T2w FLAIR image grid, 240 x 256 x 208 mm (0.0128 m3) includes non-brain tissue. The separate spatial-resolution measurement is a 290 µm PSF FWHM; it is not the sampling of this whole-brain protocol.",
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          "note": "Contrast reflects nuclear-spin relaxation time constants and water-related proton signal, detected as RF energy released while perturbed protons return to equilibrium; FLAIR sequences additionally suppress the CSF signal."
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          "text": "Proton MR spectroscopy (¹H MRS) is a noninvasive MRI-based method that estimates tissue metabolite profiles from proton signals separated by chemical shift, measured in parts per million (ppm). It chiefly detects NAA, creatine and choline, and sometimes lactate, myo-inositol and Glx (the combined glutamate and glutamine signal). The unitless signal intensities can be scaled to concentration estimates. Single-voxel STEAM (three 90° pulses, stimulated echo) and PRESS (90° excitation plus two refocusing pulses, spin echo) localize the intersection of three slices. MRSI is a hybrid spectroscopy-imaging experiment and typically uses smaller voxels with longer scans. MEGA-PRESS difference editing exploits known GABA couplings to separate its signal from stronger overlapping metabolite signals and quantify GABA, commonly at 3 T. Relative to 1.5 T, 3 T improves signal-to-noise ratio, reduces spectral overlap and makes metabolite measurement more reliable, but it also increases the chemical shift displacement error, a mismatch in where different resonances are localized. With conventional small-bandwidth refocusing pulses this displacement can exceed 30% of the voxel dimension across the 3 ppm range in one direction, even at 3 T. For applications that look for subtler metabolite changes, these conventional protocols are severely limited at 3 T and at ultra-high fields of 7 T and above."
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            "kind": "doi",
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      "description": {
        "state": "known",
        "value": {
          "text": "A Neuropixels-class probe inserts a 10-mm silicon shank (70×20 µm cross-section) carrying 960 closely spaced TiN microelectrode sites into brain tissue. Its 12×12 µm sites form a four-column checkerboard with 25 µm nearest-neighbor center spacing; 384 are simultaneously addressable. It records extracellular signals from nearby neurons, splitting each channel into spike/AP (0.3–10 kHz) and LFP (0.5–1000 Hz) bands. Such probes have been used intraoperatively in humans and chronically in freely moving mice. Neuropixels 2.0 places 1,280 sites on each 10 mm shank, and its four-shank version has 5,120 sites with 250 µm between shanks; two such probes give 10,240 sites, 768 of them recordable at once through one headstage. The ultra-dense NP Ultra layout has 5×5 µm TiN sites on a 768 × 8 grid at 6 µm center-to-center spacing."
        },
        "node": "01a15cfc-8e93-7ef2-981e-ad63d3207c36",
        "sources": [
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            "node": "01a05495-1a7f-7103-a8d6-08c7d4604811",
            "kind": "doi",
            "id": "10.1016/j.conb.2018.01.009",
            "url": "https://doi.org/10.1016/j.conb.2018.01.009"
          },
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            "node": "01a05495-24ca-75f1-b346-9b2784e4a389",
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            "url": "https://doi.org/10.1038/nature24636"
          },
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            "kind": "doi",
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            "kind": "doi",
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            "kind": "doi",
            "id": "10.1016/j.neuron.2025.08.030",
            "url": "https://doi.org/10.1016/j.neuron.2025.08.030"
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            "id": "10.1126/science.abf4588",
            "url": "https://doi.org/10.1126/science.abf4588"
          }
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        "value": {
          "min": 5e-6,
          "max": 5e-6,
          "unit": "m",
          "note": "This is a Monte Carlo point-source localization model, not a measured implanted-probe localization error. Reported Monte Carlo-modeled noise (standard deviation over trials) in spike-source position estimates for a point source with 1/R amplitude falloff, placed 15 μm from the probe, peak amplitude at the probe 50 μV, rms noise 14 μV. Reported as 5 μm for the NP Ultra probe (5×5 μm sites, 6 μm center-to-center pitch) and 25 μm for the NP 2.0 site pattern. These values are reported as the upper limit of position resolution. Units whose nearest-neighbor distances fall below the probe's spatial resolution are reported to be more difficult to sort. Standard deviations of positions in experimental data can be larger.",
          "endpoint": "localisation_error",
          "operating_points": [
            {
              "label": "NP Ultra",
              "min": 5e-6,
              "max": 5e-6,
              "note": "Reported modeled position-estimate SD of 5 μm. Ultra pattern: 5×5 μm sites at 6 μm center-to-center spacing. Model: point source 15 μm away, 1/R falloff, 50 μV peak, 14 μV rms noise. Reported as the upper limit of position resolution.",
              "endpoint": "localisation_error"
            },
            {
              "label": "NP 2.0",
              "min": 0.000025,
              "max": 0.000025,
              "note": "Reported modeled position-estimate SD of 25 μm for the NP 2.0 site pattern, under the same Monte Carlo model conditions. Reported as the upper limit of position resolution.",
              "endpoint": "localisation_error"
            }
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        "node": "01a165e1-826e-7262-81ba-1589a527495e",
        "sources": [
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            "node": "01a0e901-8146-7fd0-901e-8abbbaf58ac7",
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            "id": "10.1016/j.neuron.2025.08.030",
            "url": "https://doi.org/10.1016/j.neuron.2025.08.030"
          }
        ]
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      "temporal_resolution_s": {
        "state": "known",
        "value": {
          "min": 0.000033333333333333335,
          "max": 0.000033333333333333335,
          "unit": "s",
          "note": "Neuropixels action-potential recordings are sampled at 30 kHz, one sample every 33.3 μs, with an acquisition band of 0.3–10 kHz. LFP recordings are sampled at 2.5 kHz, or 0.4 ms per sample, with bands of 0.5–1000 Hz or 0.5–500 Hz depending on the protocol. Sampling cadence does not measure spike-time discrimination.",
          "endpoint": "sample_interval",
          "operating_points": [
            {
              "label": "LFP recording at 2.5 kHz",
              "min": 0.0004,
              "max": 0.0004,
              "endpoint": "sample_interval"
            }
          ]
        },
        "node": "01a16a46-3a5a-74a1-9ced-379af0ef54de",
        "sources": [
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            "node": "01a05495-1a7f-7103-a8d6-08c7d4604811",
            "kind": "doi",
            "id": "10.1016/j.conb.2018.01.009",
            "url": "https://doi.org/10.1016/j.conb.2018.01.009"
          },
          {
            "node": "01a05495-24ca-75f1-b346-9b2784e4a389",
            "kind": "doi",
            "id": "10.1038/nature24636",
            "url": "https://doi.org/10.1038/nature24636"
          },
          {
            "node": "01a05495-370c-79e0-a4b6-745518697d27",
            "kind": "doi",
            "id": "10.1101/2021.06.20.449152",
            "url": "https://doi.org/10.1101/2021.06.20.449152"
          }
        ]
      },
      "field_of_view_m3": {
        "state": "known",
        "value": {
          "min": 1.97e-9,
          "max": 1.97e-9,
          "unit": "m3",
          "note": "Modelled, not measured: the implant of an eight-probe simultaneous Neuropixels recording. Each probe has 384 recording channels addressing 384 of the 960 sites that tile its 10 mm shank. Stipulating a contiguous recorded stretch L = (384/960) × 10 mm = 4.0 mm and a cylinder of the ≈140 µm distance at which sites sense an action potential gives V = π(140 × 10⁻⁶ m)²(4.0 × 10⁻³ m) = 2.463 × 10⁻¹⁰ m³ per probe, and 8 × 2.463 × 10⁻¹⁰ ≈ 1.97 × 10⁻⁹ m³ for eight probes, assuming no overlap between probes.",
          "endpoint": "sensing_envelope",
          "operating_points": [
            {
              "label": "One probe, 384 of 960 sites",
              "min": 2.463e-10,
              "max": 2.463e-10,
              "note": "π(140 µm)² × 4.0 mm.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "One probe, 3.8 mm distal-most site array (chronic implant)",
              "min": 2.34e-10,
              "max": 2.34e-10,
              "note": "π(140 µm)² × 3.8 mm.",
              "endpoint": "sensing_envelope"
            }
          ]
        },
        "node": "01a15cf2-f472-7bd1-bae3-da710cb3099d",
        "sources": [
          {
            "node": "01a05495-24ca-75f1-b346-9b2784e4a389",
            "kind": "doi",
            "id": "10.1038/nature24636",
            "url": "https://doi.org/10.1038/nature24636"
          },
          {
            "node": "01a0d327-db45-7a90-9392-fed06e1e6734",
            "kind": "doi",
            "id": "10.1002/advs.202506225",
            "url": "https://doi.org/10.1002/advs.202506225"
          },
          {
            "node": "01a15ceb-3156-73a3-a7aa-983e8358d19b",
            "kind": "doi",
            "id": "10.1126/science.aav7893",
            "url": "https://doi.org/10.1126/science.aav7893"
          }
        ]
      },
      "field_of_view_neurons": {
        "state": "known",
        "value": {
          "min": 2668.0,
          "max": 2668.0,
          "unit": "neuron",
          "note": "Eight Neuropixels probes recorded simultaneously from frontal, sensorimotor, visual and retrosplenial cortex, hippocampus, striatum, thalamus and midbrain of awake mice; 2,296, 2,668 and 1,462 units stable across about an hour were extracted in three mice. The largest session yielded 2,668 units.",
          "endpoint": "sensing_envelope",
          "operating_points": [
            {
              "label": "Eight probes, three mice",
              "min": 1462.0,
              "max": 2668.0,
              "note": "Units stable across about an hour of ongoing activity.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "Two or three probes per session",
              "min": 747.0,
              "max": 747.0,
              "note": "747 ± 38 neurons per session (mean ± s.e.), n = 92 probe insertions over 39 sessions in 10 mice; units identified with Kilosort and phy.",
              "endpoint": "sensing_envelope"
            }
          ]
        },
        "node": "01a16b36-8bf1-76c3-ae2c-b4154f98cfbd",
        "sources": [
          {
            "node": "01a14c9a-1113-79d1-a936-feab937cc5bd",
            "kind": "doi",
            "id": "10.1038/s41586-019-1787-x",
            "url": "https://doi.org/10.1038/s41586-019-1787-x"
          },
          {
            "node": "01a15ceb-3156-73a3-a7aa-983e8358d19b",
            "kind": "doi",
            "id": "10.1126/science.aav7893",
            "url": "https://doi.org/10.1126/science.aav7893"
          }
        ]
      },
      "measurand": {
        "state": "known",
        "value": {
          "measurands": [
            "action potentials (spikes)",
            "local field potentials (LFPs)"
          ],
          "note": "Each channel’s continuous signal is split into AP (0.3–10 kHz) and LFP (0.5–1000 Hz) bands; isolated clusters presumably reflect one neuron or a very small number, distinguished by temporal and spatial waveforms."
        },
        "node": "01a0d90b-2a42-7ae2-9798-48b6387eb3ae",
        "sources": [
          {
            "node": "01a05495-1a7f-7103-a8d6-08c7d4604811",
            "kind": "doi",
            "id": "10.1016/j.conb.2018.01.009",
            "url": "https://doi.org/10.1016/j.conb.2018.01.009"
          },
          {
            "node": "01a05495-24ca-75f1-b346-9b2784e4a389",
            "kind": "doi",
            "id": "10.1038/nature24636",
            "url": "https://doi.org/10.1038/nature24636"
          },
          {
            "node": "01a05495-3584-76c1-a96f-6f9907408b5c",
            "kind": "doi",
            "id": "10.1038/s41593-021-00997-0",
            "url": "https://doi.org/10.1038/s41593-021-00997-0"
          },
          {
            "node": "01a05495-370c-79e0-a4b6-745518697d27",
            "kind": "doi",
            "id": "10.1101/2021.06.20.449152",
            "url": "https://doi.org/10.1101/2021.06.20.449152"
          }
        ]
      },
      "stimulation": {
        "state": "incomplete"
      },
      "destructiveness": {
        "state": "known",
        "value": {
          "kind": "minimally_destructive",
          "note": "The shank is designed to minimize tissue damage; actual displacement or damage was not quantified. No complications were observed in 56 patients, and one-case histology showed minimal insertion evidence."
        },
        "node": "01a0d90b-dfc3-7591-8cc5-f876cf4ec4ad",
        "sources": [
          {
            "node": "01a05495-1a7f-7103-a8d6-08c7d4604811",
            "kind": "doi",
            "id": "10.1016/j.conb.2018.01.009",
            "url": "https://doi.org/10.1016/j.conb.2018.01.009"
          },
          {
            "node": "01a05495-24ca-75f1-b346-9b2784e4a389",
            "kind": "doi",
            "id": "10.1038/nature24636",
            "url": "https://doi.org/10.1038/nature24636"
          },
          {
            "node": "01a05495-41d1-7753-859d-2174b4afbfde",
            "kind": "doi",
            "id": "10.3171/2025.4.jns241162",
            "url": "https://doi.org/10.3171/2025.4.jns241162"
          }
        ]
      },
      "preparation": {
        "state": "known",
        "value": {
          "steps": [
            {
              "kind": "surgery",
              "note": "Stereotactically guided probe insertion through a burr hole or craniotomy during resection or DBS surgery; in the 56-case series, insertion was into tissue slated for resection."
            },
            {
              "kind": "other",
              "note": "Sterilize the probe."
            },
            {
              "kind": "other",
              "note": "Provide operating-room electrical isolation."
            },
            {
              "kind": "other",
              "note": "Address brain pulsation during probe use."
            }
          ],
          "note": "Human intraoperative Neuropixels requires surgical access and operating-room preparation."
        },
        "node": "01a0d90c-8dec-7a71-8a56-bd7284b3f8aa",
        "sources": [
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            "kind": "doi",
            "id": "10.1101/2021.06.20.449152",
            "url": "https://doi.org/10.1101/2021.06.20.449152"
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            "kind": "doi",
            "id": "10.3171/2025.4.jns241162",
            "url": "https://doi.org/10.3171/2025.4.jns241162"
          }
        ]
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      "cost": {
        "state": "known",
        "items": [
          {
            "value": {
              "currency": "EUR",
              "amount_min": 7250.0,
              "amount_max": 7250.0,
              "label": "Box of 5 Neuropixels 1.0 probes, imec request-for-quotation unit price"
            },
            "node": "01a15d02-6d28-74f0-9eea-8b7801f09ca2",
            "sources": [
              {
                "node": "01a15cff-b209-7e43-8aef-194e2ee1512f",
                "kind": "url",
                "id": "https://neuropixels.org/_files/ugd/328966_6dad3ee0d9014e34a11a07cb85e3febf.pdf",
                "url": "https://neuropixels.org/_files/ugd/328966_6dad3ee0d9014e34a11a07cb85e3febf.pdf"
              }
            ]
          },
          {
            "value": {
              "currency": "EUR",
              "amount_min": 8250.0,
              "amount_max": 8250.0,
              "label": "Box of 5 Neuropixels 2.0 multishank probes, imec request-for-quotation unit price"
            },
            "node": "01a15d03-91d2-78c2-b531-27e53d90452e",
            "sources": [
              {
                "node": "01a15cff-b598-79f0-9e72-a5dace5d027c",
                "kind": "url",
                "id": "https://neuropixels.org/_files/ugd/328966_f29e2d0b95da498c9d88e21f262d50ec.pdf",
                "url": "https://neuropixels.org/_files/ugd/328966_f29e2d0b95da498c9d88e21f262d50ec.pdf"
              }
            ]
          },
          {
            "value": {
              "currency": "EUR",
              "amount_min": 320.0,
              "amount_max": 320.0,
              "label": "Neuropixels 2.0 headstage, imec request-for-quotation unit price (the 1.0 headstage is also 320)"
            },
            "node": "01a15d04-d4b3-7ca2-bbb5-7729a35d6515",
            "sources": [
              {
                "node": "01a15cff-b209-7e43-8aef-194e2ee1512f",
                "kind": "url",
                "id": "https://neuropixels.org/_files/ugd/328966_6dad3ee0d9014e34a11a07cb85e3febf.pdf",
                "url": "https://neuropixels.org/_files/ugd/328966_6dad3ee0d9014e34a11a07cb85e3febf.pdf"
              },
              {
                "node": "01a15cff-b598-79f0-9e72-a5dace5d027c",
                "kind": "url",
                "id": "https://neuropixels.org/_files/ugd/328966_f29e2d0b95da498c9d88e21f262d50ec.pdf",
                "url": "https://neuropixels.org/_files/ugd/328966_f29e2d0b95da498c9d88e21f262d50ec.pdf"
              }
            ]
          },
          {
            "value": {
              "currency": "EUR",
              "amount_min": 4460.0,
              "amount_max": 4460.0,
              "label": "Neuropixels OneBox acquisition system, imec request-for-quotation unit price"
            },
            "node": "01a15d05-f864-7661-ac85-348d1b070d93",
            "sources": [
              {
                "node": "01a15cff-b598-79f0-9e72-a5dace5d027c",
                "kind": "url",
                "id": "https://neuropixels.org/_files/ugd/328966_f29e2d0b95da498c9d88e21f262d50ec.pdf",
                "url": "https://neuropixels.org/_files/ugd/328966_f29e2d0b95da498c9d88e21f262d50ec.pdf"
              }
            ]
          }
        ]
      },
      "theoretical": {
        "description": {
          "state": "known",
          "value": {
            "text": "Spatially, the best-case modelled precision for locating a spike source is about 5 µm (standard deviation of the position estimate) for the dense NP Ultra layout (5×5 µm sites, 6 µm pitch), and about 25 µm for the coarser NP 2.0 layout. These are Monte Carlo figures for a 1/R point source 15 µm from the probe, with 50 µV peak amplitude and 14 µV rms noise, described as the upper limit of position resolution; experimental scatter can be larger.\n\nTemporally, in 11 somatic paired recordings in hippocampus in vivo with wideband (1 Hz-3 kHz) filtering, the cell-to-cell standard deviation of the offset between extracellular and intracellular waveform landmarks ranged from 0.02 ms at spike onset to 0.14 ms at spike end. These are offsets between averaged waveforms, not spike-by-spike jitter, and the extracellular negative peak leads the intracellular peak by 0.20 ms.\n\nCoverage: two four-shank Neuropixels 2.0 probes on one headstage (10,240 sites, 768 recordable at once) would sense about 4.8 × 10⁻⁹ m³ (about 4.8 mm³) if every site along the 10 mm shanks were counted and each shank sensed a cylinder of the ≈140 µm action-potential sensing distance, with overlap between shanks 250 µm apart removed and no overlap between the two probes. One single-shank probe gives about 0.62 mm³ under the same model. These are geometric estimates, not measured volumes."
          },
          "node": "01a15cf7-c5ea-7242-bd42-2c22d807703a",
          "sources": [
            {
              "node": "01a0d327-db45-7a90-9392-fed06e1e6734",
              "kind": "doi",
              "id": "10.1002/advs.202506225",
              "url": "https://doi.org/10.1002/advs.202506225"
            },
            {
              "node": "01a0d352-3b18-7e62-aeb4-63746ea1a9de",
              "kind": "doi",
              "id": "10.1152/jn.2000.84.1.390",
              "url": "https://doi.org/10.1152/jn.2000.84.1.390"
            },
            {
              "node": "01a0e901-8146-7fd0-901e-8abbbaf58ac7",
              "kind": "doi",
              "id": "10.1016/j.neuron.2025.08.030",
              "url": "https://doi.org/10.1016/j.neuron.2025.08.030"
            },
            {
              "node": "01a15ceb-352f-78c1-971e-2df2627861c6",
              "kind": "doi",
              "id": "10.1126/science.abf4588",
              "url": "https://doi.org/10.1126/science.abf4588"
            }
          ]
        },
        "spatial_resolution_m": {
          "state": "known",
          "value": {
            "max": 5e-6,
            "unit": "m",
            "note": "Best-case modeled spike-source position resolution for Neuropixels-class probes: about 5 µm (standard deviation of the position estimate) for the NP Ultra pattern (5×5 µm sites, 6 µm pitch). The figure comes from a Monte Carlo model of a 1/R point source placed 15 µm from the probe, with 50 µV peak amplitude and 14 µV rms noise. It is a model value, not an experimental measurement, and is described as the upper limit of position resolution; experimental position scatter can be larger. Denser sampling improves it because more sites fall within the 60 µm fit radius, which reduces the impact of noise. By contrast, the coarser NP 2.0 pattern gives about 25 µm under the same model.",
            "endpoint": "localisation_error",
            "operating_points": [
              {
                "label": "Model-based, NP Ultra pattern (5×5 µm sites, 6 µm pitch); point source at 15 µm, 50 µV peak, 14 µV rms noise",
                "max": 5e-6,
                "note": "Monte Carlo standard deviation of the position estimate. It is a best-case figure, and experimental scatter can be larger. The coarser NP 2.0 pattern gives about 25 µm under the same conditions.",
                "endpoint": "localisation_error"
              }
            ]
          },
          "node": "01a15142-da71-7763-be5c-c6342ee2fa09",
          "sources": [
            {
              "node": "01a0e901-8146-7fd0-901e-8abbbaf58ac7",
              "kind": "doi",
              "id": "10.1016/j.neuron.2025.08.030",
              "url": "https://doi.org/10.1016/j.neuron.2025.08.030"
            }
          ]
        },
        "temporal_resolution_s": {
          "state": "incomplete"
        },
        "field_of_view_m3": {
          "state": "known",
          "value": {
            "min": 4.773e-9,
            "max": 4.773e-9,
            "unit": "m3",
            "note": "Geometric estimate, not a measured volume, for the largest single-headstage configuration described: two four-shank Neuropixels 2.0 probes (10,240 sites, 768 recordable simultaneously). Stipulations: every site along each 10 mm shank is counted, though only 768 can be recorded at once; each shank senses a cylinder of the ≈140 µm distance at which sites sense an action potential; the two probes do not overlap. Per shank the cross-section is π(140 µm)² = 61,575 µm². Shanks 250 µm apart overlap, since 2 × 140 µm > 250 µm; the lens shared by two neighbouring circles is 2r²·acos(d/2r) − (d/2)·√(4r² − d²) = 2,550 µm² for r = 140 µm, d = 250 µm. Four shanks in a row give 4 × 61,575 − 3 × 2,550 = 238,650 µm², times 10 mm = 2.387 × 10⁻⁹ m³ per probe, and 4.773 × 10⁻⁹ m³ for two probes.",
            "endpoint": "reachable_envelope",
            "operating_points": [
              {
                "label": "One four-shank Neuropixels 2.0 probe (5,120 sites)",
                "min": 2.387e-9,
                "max": 2.387e-9,
                "note": "238,650 µm² × 10 mm.",
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              "min": 3.5e-6,
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            {
              "label": "Axial optical resolution in air",
              "min": 4.7e-6,
              "max": 4.7e-6,
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    {
      "slug": "oct-retinal",
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          "text": "Retinal optical coherence tomography (OCT) is a non-invasive optical imaging technique that produces cross-sectional images with near-histological resolution and a penetration depth of a few millimeters. It relies on low-coherence interferometry: light from a broadband source is split between a reference arm and the eye, and the interference between light reflected from the reference arm and light backscattered or backreflected from retinal tissue is measured. In spectral/Fourier-domain systems, this interference is captured as a spectrum with a spectrometer and line-scan camera; taking its Fourier transform recovers the echo time delay and magnitude of light returning from each depth in the tissue, without needing to mechanically scan the reference arm. Scanning this measurement across the retina builds up high-resolution two-dimensional cross-sectional images and reproducible three-dimensional volumetric data of the retina and optic nerve head. The axial (depth) resolution is set by the coherence length of the light source, which is inversely proportional to its spectral bandwidth, so broader-bandwidth sources give finer axial resolution. From the resulting volumes, quantitative measurements such as retinal and optic-nerve-head layer thicknesses are extracted, including the inner retinal nerve fiber layer and ganglion cell-inner plexiform layer, which thin in neurodegenerative disease."
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          "note": "Retinal OCT axial image resolution. Ultrahigh-resolution OCT with a 150 nm FWHM bandwidth was measured at 2.6 µm in air, which corresponds to approximately 2 µm in retinal tissue. The source describes standard commercial instruments current at its 2005 publication as having about 10 µm resolution.",
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              "label": "Ultrahigh-resolution OCT, retinal tissue",
              "min": 2e-6,
              "max": 2e-6,
              "note": "Approximate (~2 µm), derived from the measured air value."
            },
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              "label": "Ultrahigh-resolution OCT, air",
              "min": 2.6e-6,
              "max": 2.6e-6,
              "note": "Measured 2.6 µm with 150 nm FWHM optical bandwidth."
            },
            {
              "label": "Standard commercial OCT (as of 2005 source)",
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          "min": 0.005,
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          "note": "An in-vivo retinal FDML-OCT experiment acquired individual wide B-scans in 5 ms at 200 Hz; averaging takes multiple frames.",
          "endpoint": "sample_interval",
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            {
              "label": "High-definition prototype B-scan",
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          "unit": "m3",
          "note": "Retinal VCSEL-OCT at 580 kHz: 12 x 12 mm scan area times the 1.9 mm tissue imaging range gives 273.6 mm3. This is the acquisition box, not a segmented retinal volume.",
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            {
              "label": "Earlier raster protocol",
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          "kind": "non_destructive",
          "note": "Retinal OCT is non-invasive and analyzes backscattered light. Specifically, the DeepLive device safety study found IEC 60825-1 MPE compliance and no observed phototoxicity or retinal tissue damage."
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          "note": "No required dilation: minimum pupil size is 2 mm and is usually achieved without it. If dilation is used and quantitative comparisons are planned, use it at subsequent visits for repeatability. The subject focuses on the green-star target, blinks naturally during alignment, then blinks and opens the eyes wide for acquisition."
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      "cost": {
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      "slug": "open-resection",
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          "text": "Open brain resection incises and removes (resects) brain tissue; related open procedures may sacrifice or disconnect tissue, e.g., hemispherotomy disconnects without complete removal. Anatomical variants include lesion/glioma resection, partial anterior temporal lobectomy with amygdalectomy, standard ATL (removing temporal neocortex, amygdala, hippocampus and parahippocampal gyrus), and selective amygdalohippocampectomy, which spares lateral neocortex. Adjuncts include awake craniotomy for direct stimulation and real-time functional mapping, neuronavigation, and sometimes intraoperative MRI or electrocorticography (ECoG); awake feasibility varies and ECoG benefit is disputed. Open resection can maximize lesion removal but carries greater morbidity and limited repeatability."
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          "note": "Mouse holographic optogenetics accesses sparse neuronal targets across three planes in a 550 × 550 × 100 μm box. The box lies well within stimulation reach, so its nominal volume is a lower bound, not continuously illuminated or uniformly suprathreshold tissue.",
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          "note": "In one example mouse, a single-phase-mask two-photon hologram (ChroME2s in L2/3 pyramidal neurons, up to 4 W total at 1,040 nm, targets chosen from the top 30% most excitable neurons) increased calcium signals in 346 of 408 targeted neurons simultaneously.",
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            "GCaMP6s calcium fluorescence by imaging"
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          "note": "Light delivery is the intervention. In ChR2-expressing mammalian neurons, light controlled millisecond spiking. In mouse cortex, multiphoton ST-ChroME stimulation evoked spikes and increased GCaMP6s fluorescence, while IRES-ST-eGtACR1 suppressed identified neurons in vivo. Rare motion caused failures or off-target activation, and coincident trials were excluded."
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            "3D-SHOT multiphoton illumination delivered to in vivo cortical neurons expressing soma-targeted ChroME or IRES-ST-eGtACR1"
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          "note": "In lentivirally transduced mammalian neurons, ChR2 light-gated cation conductance enables reliable millisecond spike control. ChroME supports high-fidelity sub-millisecond control of pyramidal-neuron spiking; the in-vivo 3D-SHOT ensemble demonstration used soma-targeted ChroME with millisecond precision. The 3 ms timing figure is an independently controlled across-cell offset in a two-cell fast-SLM protocol, with each train averaging 10 Hz. IRES-ST-eGtACR1 recruits inhibitory anion conductance to silence identified cortical neurons with high fidelity."
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          "note": "The described in-vivo mouse all-optical preparations are minimally destructive: viral delivery penetrates cortex through a burr hole, while head-plate and window surgery removes scalp and skull and causes bleeding; neural-tissue ablation is not the protocol’s purpose."
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              "note": "Inject AAV encoding the opsin and, depending on the combination, Cre or GCaMP6. Use mice 2–6 weeks after opsin injection or 1–2 weeks after GCaMP6 injection."
            },
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              "note": "For specified combinations, use inherited CamKII-tTA × tetO-GCaMP6s, CamKII-tTA × tetO-GCaMP6s × Emx1-Cre, or PV-Cre mice. These lines are protocol-specific and distinct from somatic viral expression."
            },
            {
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            },
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              "note": "Fit a stainless-steel headplate, make a 3 mm craniotomy over left primary somatosensory cortex and permanently seal it with a coverslip window."
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              "note": "Allow heated recovery. Starting two days after surgery, habituate mice to head fixation over a freely moving circular treadmill for 2–7 days; subsequent calcium imaging is head-fixed on a freely spinning wheel."
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            "text": "For holographic two-photon optogenetics, the number of neurons driven at once is bounded by laser power: a maximal total instantaneous laser energy of 4 W at the sample (1,040 nm) is shared among targets, and the power needed per cell depends on the opsin (in vivo ED50s of about 12 mW for ChroME2s, 22 mW for ChroME2f and 88 mW for ChroME). Under these conditions one 408-target hologram increased activity in 346 neurons.\n\nThe reachable volume is set by the optics. On one mesoscope, single-field holographic targeting spans about 950 µm × 990 µm laterally, the farthest hologram positions without aliasing, and 220 µm axially, a digital defocusing range over which axial point-spread functions stay mostly invariant: about 2.07 × 10⁻¹⁰ m³. Diffraction efficiency falls toward the field edges and per-spot power is adjusted by location to compensate. The single-spot point-spread function is about 9 µm laterally and 32 µm axially. This box is not a uniformly suprathreshold tissue volume and not a fundamental bound on every microscope."
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          "value": {
            "min": 2.0691e-10,
            "max": 2.0691e-10,
            "unit": "m3",
            "note": "Conditional nominal bounding box for single-field holographic targeting on the 2p-RAM mesoscope, from optical hologram characterization: about 950 µm × 990 µm × 220 µm = about 2.07e8 µm³ (about 0.207 mm³). The lateral extent is the farthest hologram position without aliasing and closely approximates the theoretical SLM field at this magnification. Diffraction efficiency falls toward the field edges, and per-spot power is adjusted by location to compensate. The 220 µm axial range is a digital defocusing range over which axial PSFs stay mostly invariant. Mesoscope field curvature is 160 µm over the 5 mm field. Holographic field flatness has about 40 µm maximal peak-to-valley, which lies within the SLM defocus range and is correctable. Single-spot PSF is about 9 µm laterally and 32 µm axially. This box is not a uniformly suprathreshold tissue volume and not a fundamental bound on every microscope.",
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      "group": {
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        "value": "Short laser pulses are absorbed mainly by haemoglobin in blood, briefly heating it so it emits ultrasound pressure waves. A detector picks up these generated waves, and their one-way acoustic travel time gives depth. In mouse cortex, imaged through intact skull, a cranial window, or noninvasively through scalp and skull, it reads vessel structure, diameter, blood oxygenation, flow and estimated oxygen metabolism, reaching about 0.7 mm through skull. These are haemodynamic measures, not direct neuronal readouts; neuronal calcium activity requires added fluorescence imaging.",
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          "text": "Photoacoustic microscopy (PAM) is a focused-scanning form of photoacoustic imaging. Absorbed light, mainly by hemoglobin at 532 nm, becomes heat. The heat launches pressure waves that an ultrasonic transducer detects, and acoustic flight time gives depth, so each laser pulse yields a 1D depth profile. In the optical-resolution form, lateral resolution is set by the optical focus: ~3–7 μm, with ~15 μm axial resolution. Scanning methods include a MEMS mirror combined with a stage, a polygon scanner combined with a stage, and uniform rotary scanning. In mouse cortex, it measures vessel structure, diameter, perfusion, oxygen saturation, oxygen extraction, flow, and estimated oxygen metabolism. Depth reached ~0.7 mm through intact skull, and capillary resolution degrades with depth. Paired with fluorescence, it relates these signals to neuronal calcium activity. In the acoustic-resolution regime, the ultrasound detector sets resolution: a 20 MHz detector gave 70 μm lateral resolution. That system used raster scanning to track vessel oxygenation noninvasively through scalp and skull."
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          "note": "Finest lateral resolution is ~3 μm at the optical focus for MEMS-scanned optical-resolution photoacoustic microscopy of mouse brain, achieved in clear media. Lateral resolution degrades with depth in brain tissue due to scattering, and the skull blurs optical focusing. Other instruments give coarser figures, mostly measured from bead FWHMs or in vivo vessel profiles.",
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              "note": "~3 μm. Degrades with imaging depth in brain tissue and through skull.",
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              "note": "~15 μm. Set by laser pulse width, acoustic attenuation and transducer response.",
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            {
              "label": "Linear-array hybrid PAM/confocal fluorescence microscope, lateral (6 mm × 5 mm FOV)",
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              "max": 7e-6,
              "note": "Measured ~6 μm for both PAM and confocal fluorescence: ~5.7 μm at the center to ~7 μm at the edge. Simulated value is 5.76 μm.",
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              "label": "Rotary-scanning multimodal OR-PAM, lateral (Ø8.6 mm FOV)",
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              "note": "Mean 7.1 ± 0.8 μm from 1-μm bead FWHMs: 5.8 μm at the center, 9.2 μm at the edges. Widefield fluorescence channel is 10.7 ± 3.1 μm. At 4 Hz, sparse sampling degrades resolution to 17.5 μm; upsampling recovery restores it to close to the mean, as a restored image.",
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              "endpoint": "point_spread"
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              "note": "Isotropic resolution of ~32 μm from multiangle synthetic bead PSF across the FOV. In vivo resolution through intact scalp and skull is 33 μm. Single-angle data give 27 μm optical resolution perpendicular to the line and 300 μm acoustic resolution parallel to it.",
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          "note": "MEMS OR-PAM produces a cross-sectional image every 0.0025 s (400 Hz) over a roughly 3 mm scan. This is an image sample interval with smaller spatial coverage than full-field or volumetric acquisitions, not neural-event separation. Rotary-scanning OR-PAM produces full-field en-face images every 0.25 s (4 Hz); other volumetric regimes take 0.5 or 1 s per volume.",
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              "label": "MEMS OR-PAM mouse brain, 5 × 10 mm field",
              "min": 15.0,
              "max": 15.0,
              "note": "Approximately 15 s per scanned image through intact skull with scalp removed.",
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              "min": 0.25,
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              "note": "4 Hz en-face image cadence verified with flowing ink. Sparse sampling degrades lateral resolution to 17.5 µm; upsampling reconstruction restores it close to the average calibration. The separate 3 µm lateral optical-focus result concerns MEMS OR-PAM in clear media.",
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            {
              "label": "Ultrafast functional PAM, 11 × 7.5 × 1.5 mm volume",
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          "note": "Ultrafast functional photoacoustic microscopy acquired an 11 × 7.5 × 1.5 mm volume at 2 Hz with approximately 10 µm spatial resolution. The acquisition box is 123.75 mm³. The approximately 10 µm resolution belongs to this volumetric acquisition; the approximately 3 µm lateral optical-focus resolution is a separate MEMS OR-PAM result in clear media.",
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          "note": "Absorbed laser energy is converted to heat, generating a pressure (ultrasound) wave detected by a transducer; at 532 nm hemoglobin absorption exceeds that of water and lipids by ~three orders of magnitude, giving vascular contrast, and depth is inferred from acoustic flight time along the acoustic axis."
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          "note": "The high-resolution protocols damage tissue incidentally through surgery, not by design. One study removed the scalp and left the skull intact, imaging at ~3 μm lateral resolution. Others imaged through cranial windows at ~6–7 μm. In one mouse study, imaged red blood cells stayed intact. Two-photon imaging after a deliberate 1000 nJ pulse showed no bleeding. H&E histology showed no burns in the imaged area, compared against a deliberately burned control. Another study reported that its sparse-sampling strategy avoided heat damage. Lower-resolution alternatives imaged mice through intact scalp and skull: near-infrared mesoscopy at ~33 μm, and acoustic-resolution PAM at 70 μm lateral and 54 μm axial."
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              "note": "Water-circulating heating pad at 37 °C; animal taped to holder; head fixed in stereotaxic frame (MEMS PAM)"
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          "note": "Fast functional MEMS-scanning PAM: mouse anesthetized with intraperitoneal α-chloralose (100 mg/kg), kept at 37 °C, head fixed in a stereotaxic frame, and scalp surgically removed with skull intact. The skull is cleaned with PBS and coated with ultrasound gel, and a de-ionized-water tank with a membrane bottom touches the gel for acoustic coupling. multiScope OR-PAM images the cortex through a cranial window in mice head-fixed on a treadmill. 570-nm acoustic-resolution PAM and NIR PACMes image noninvasively, PACMes through intact scalp and skull."
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            "text": "Optical scattering in brain tissue degrades lateral resolution and contrast with depth, as in any depth-resolved optical microscopy. In one high-speed optical-resolution microscope imaging mouse brain through intact skull, this left deep capillaries unresolved, the skull blurred focusing and attenuated signal, measured depth was ~0.7 mm (~0.75 mm stated as approximate maximum), and acoustic sectioning was poorer than two-photon optical sectioning. Optical attenuation also limits pulse-width oxygenation depth. Axial resolution depends on laser pulse width, frequency-dependent acoustic attenuation and transducer response. Strong high-frequency ultrasound attenuation creates a resolution–penetration trade-off. Speed is constrained because extending focal range by depth scanning costs speed, and coarser scan steps used for faster imaging degrade resolution through undersampling."
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    {
      "slug": "photoacoustic-tomography",
      "name": "Photoacoustic tomography",
      "group": {
        "id": "optical",
        "name": "Optical & ultrasound (in vivo)"
      },
      "mode": "read",
      "core": true,
      "summary": {
        "value": "Photoacoustic brain imaging sends brief laser pulses into tissue; light absorbed, mostly by haemoglobin, briefly heats and expands it, emitting ultrasound that surrounding detectors record to reconstruct absorption maps. Multiple wavelengths separate oxygenated from deoxygenated blood, giving blood volume and oxygenation, which track neural activity only indirectly through blood-flow coupling. In transgenic mice carrying a calcium indicator, absorption changes also tracked calcium transients, only about 1.5 mm deep. Animals were imaged through skin and skull, thinned skull, or partial bone removal; human functional imaging required a missing skull section.",
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      "description": {
        "state": "known",
        "value": {
          "text": "Photoacoustic computed tomography delivers wide, diffuser- or multi-fibre-spread pulsed light; absorbed light causes thermoelastic ultrasound recorded by surrounding detector arrays, with images reconstructed by back-projection. Label-free readout uses multiwavelength haemoglobin contrast (HbO2, HbR, total haemoglobin, sO2, blood volume, connectivity) via neurovascular coupling. Separately, absorption by genetically encoded GCaMP reports calcium transients in transgenic mice. Mouse imaging spanned intact skin and skull, thinned skull, or partial parietal bone removal; rat imaging used thinned skull for angiography and intact skull for functional imaging. Human functional imaging was performed in post-hemicraniectomy patients through the skull defect; transcranial adult imaging is described only as potential, requiring further improvement."
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        "value": {
          "min": 0.000068,
          "max": 0.000074,
          "unit": "m",
          "note": "Finest measured in-plane PSF: arc-shaped fiber ultrasound transducer (FUT) PACT, ~68 μm axial and ~74 μm lateral, calibrated with 10 μm polystyrene dyed microspheres. This is 2D sectioning; elevational slice thickness is ~400 μm, so it is not 3D isotropic.",
          "endpoint": "point_spread",
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            {
              "label": "FUT PACT, fine cortical mouse imaging (thinned skull)",
              "min": 0.00007,
              "max": 0.00007,
              "note": "~70 μm in the cerebral cortex region of BALB/c mice with thinned skull, 532 nm; 2D section imaging",
              "endpoint": "point_spread"
            },
            {
              "label": "FUT PACT elevational slice thickness",
              "min": 0.0004,
              "max": 0.0004,
              "note": "~400 μm sheet-like focus in the elevational direction; out-of-plane sectioning, not in-plane resolution",
              "endpoint": "focal_extent"
            },
            {
              "label": "512-element spherical array, noninvasive whole-mouse-brain system",
              "min": 0.00015,
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              "note": "Nearly isotropic 3D ~150 μm at the array center; agar phantom with ~50 μm polyethylene spheres (FWHM corrected for diameter); ~2 cm^3 FOV; used in excised brains and through intact skin and skull in vivo",
              "endpoint": "point_spread"
            },
            {
              "label": "3D-PanoPACT (brain imaged after ~8 mm parietal bone removal)",
              "min": 0.0001786,
              "max": 0.0003123,
              "note": "10 μm tungsten wire, Gaussian FWHM: lateral 178.6 μm at center degrading to 312.3 μm at 15 mm radial; axial stable ~250 μm; called near-isotropic within 15 mm radius; 0.1 mm reconstruction voxels",
              "endpoint": "point_spread"
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            {
              "label": "3D-PACT rat brain (skull thinned for angiography, intact for functional)",
              "min": 0.00037,
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              "note": "50 μm aluminum particle after calibration: 390 μm in X–Y plane, 370 μm along Z",
              "endpoint": "point_spread"
            },
            {
              "label": "1K3D-fPACT human, post-hemicraniectomy",
              "min": 0.00035,
              "max": 0.00035,
              "note": "350 μm isotropic PSF FWHM measured in acoustically homogeneous D2O; 10 cm diameter FOV",
              "endpoint": "point_spread"
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      "temporal_resolution_s": {
        "state": "known",
        "value": {
          "min": 0.04,
          "max": 0.04,
          "unit": "s",
          "note": "In vivo mouse GCaMP optoacoustic imaging with the 512-element spherical matrix used 25 Hz laser repetition at 488 nm, giving a 0.04 s volume interval. The device can reach 100 volumes/s at its maximum laser repetition rate; that is not the in-vivo GCaMP acquisition rate.",
          "endpoint": "sample_interval",
          "operating_points": [
            {
              "label": "Spherical array, device maximum laser-limited volume rate",
              "min": 0.01,
              "max": 0.01,
              "note": "100 volumes/s is the stated maximum set by laser repetition, not the in-vivo GCaMP acquisition rate.",
              "endpoint": "sample_interval"
            },
            {
              "label": "Spherical array, in vivo mouse GCaMP (25 Hz, 488 nm)",
              "min": 0.04,
              "max": 0.04,
              "note": "Single wavelength at 25 Hz laser repetition rate.",
              "endpoint": "sample_interval"
            },
            {
              "label": "Spherical array, haemodynamics: per-pulse spacing (20 Hz)",
              "min": 0.05,
              "max": 0.05,
              "note": "Individual wavelength pulses at 20 Hz.",
              "endpoint": "sample_interval"
            },
            {
              "label": "Spherical array, haemodynamics: full five-wavelength cycle",
              "min": 0.25,
              "max": 0.25,
              "note": "Five wavelengths at 20 Hz give 4 Hz per wavelength, i.e. one complete multispectral cycle every 0.25 s.",
              "endpoint": "sample_interval"
            },
            {
              "label": "PanoPACT single-wavelength 1064 nm mode",
              "min": 0.04,
              "max": 0.04,
              "note": "Maximum 25 Hz pulse repetition rate; one volume per laser excitation.",
              "endpoint": "sample_interval"
            },
            {
              "label": "PanoPACT dual-wavelength mode",
              "min": 0.1,
              "max": 0.1,
              "note": "10 Hz paired pulses, limited by the OPO crystal damage threshold. Brain imaging in this system used STINT array rotation, for which no volume rate is stated.",
              "endpoint": "sample_interval"
            },
            {
              "label": "Rat whole-brain functional 3D-PACT",
              "min": 2.0,
              "max": 2.0,
              "note": "0.5 Hz volumetric rate.",
              "endpoint": "sample_interval"
            },
            {
              "label": "Human post-hemicraniectomy functional mode (1K3D-fPACT)",
              "min": 2.0,
              "max": 2.0,
              "note": "0.5 Hz reciprocal 90° rotation.",
              "endpoint": "sample_interval"
            },
            {
              "label": "Rat anatomical volume",
              "min": 5.0,
              "max": 5.0,
              "note": "The rat system's volumetric scan time ranges from 2 to 10 s depending on FOV.",
              "endpoint": "acquisition_duration"
            },
            {
              "label": "Human baseline scans",
              "min": 10.0,
              "max": 108.0,
              "note": "10 s single breath-hold anatomical scan; 108 s for ten dual-wavelength baseline images.",
              "endpoint": "acquisition_duration"
            },
            {
              "label": "Mouse OA GCaMP6f evoked response peak",
              "min": 0.36,
              "max": 0.36,
              "note": "Peak at about 360 ms after a 50 ms hind-paw stimulus; signal returns to baseline at about 0.8 s.",
              "endpoint": "response_latency"
            },
            {
              "label": "Human PA onset (time to 50% peak)",
              "min": 6.1,
              "max": 6.5,
              "note": "HbT 6.1 ± 0.7 s; sO2 6.5 ± 0.6 s.",
              "endpoint": "response_latency"
            }
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        ]
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      "field_of_view_m3": {
        "state": "known",
        "value": {
          "min": 2e-6,
          "max": 2e-6,
          "unit": "m3",
          "note": "Effective instrument FOV of ~2 cm^3 (~2e-6 m^3) for the 512-element, 40 mm-radius, 140° spherical array (5 MHz), designed to cover the entire mouse brain. It was estimated in an agar phantom with sparse ~50 μm polyethylene absorbing spheres, as the size of the region containing particles reconstructed above 50% of maximum image signal. It is a phantom calibration figure, not a measured brain-tissue volume. In vivo, contrast depth was ~1.5 mm at 488 nm and ~7 mm at 650 nm; these are tissue penetration depths, not FOV.",
          "endpoint": "sensing_envelope"
        },
        "node": "01a161fc-ac30-75e0-aa8b-93efd236cad9",
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        "state": "incomplete"
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      "measurand": {
        "state": "known",
        "value": {
          "measurands": [
            "optical absorption (via laser-induced ultrasound)",
            "oxyhemoglobin and deoxyhemoglobin concentration",
            "total hemoglobin / cerebral blood volume",
            "blood oxygen saturation (sO2)",
            "GCaMP calcium-dependent absorption change"
          ],
          "note": "Photoacoustic tomography detects ultrasound waves produced when absorbed pulsed laser light causes thermoelastic expansion, and from these it reconstructs the distribution of optical absorption, not fluorescence emission. In brain tissue the contrast comes mainly from hemoglobin, which shows up as vascular images. Using several wavelengths, the signal can be unmixed into HbO2 and HbR. From these, total hemoglobin (proportional to blood volume, reported as CBV) and sO2 can be derived. These are haemodynamic proxies of neural activity through neurovascular coupling, demonstrated in rats and in post-hemicraniectomy human patients validated against 7 T fMRI. Separately, in GCaMP6f/6s mice imaged at a single 488 nm wavelength, one system recorded stimulus-locked optoacoustic signal transients that peaked about 360 ms after brief 50 ms hind-paw pulses and paralleled the separately recorded fluorescence responses. Wild-type mice showed no optoacoustic change under the same paradigm, supporting a calcium-indicator origin of those transients rather than a haemodynamic one. At 488 nm, clear contrast was preserved only to about 1.5 mm depth, against heavy blood background absorption."
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        "state": "incomplete"
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          "kind": "minimally_destructive",
          "note": "Light delivery and ultrasound detection are applied from outside the head. In one mouse study, whole-brain calcium recordings were made through intact skin and skull at about 3 mJ/cm^2 fluence at the scalp. Some protocols add incidental, local surgical damage: an 8 mm parietal bone removal with the scalp sutured and the dura spared (mouse), skull thinning (mouse), or scalp removal with a thinned but intact skull (rat). Human imaging used existing hemicraniectomy windows. Reported fluences were within ANSI limits."
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      "preparation": {
        "state": "known",
        "value": {
          "steps": [
            {
              "kind": "germline_genetic_engineering",
              "note": "GCaMP mice: transgenic GCaMP6f/6s-expressing mice imaged through intact skin and skull."
            },
            {
              "kind": "other",
              "note": "GCaMP mice: a 100 μm black microsphere placed just above the skin for per-pulse laser energy normalization."
            },
            {
              "kind": "anesthesia",
              "note": "Rat: maintained under 1.5% vaporized isoflurane, with ophthalmic ointment over the eyes."
            },
            {
              "kind": "surgery",
              "note": "Rat anatomy: head hair removed with clippers and depilatory cream; scalp opened; cranial surface thinned with a handheld drill and polished with a green stone burr."
            },
            {
              "kind": "surgery",
              "note": "Rat functional imaging: top part of the scalp removed with the skull kept intact."
            },
            {
              "kind": "other",
              "note": "Rat: 3D-printed nose cone and tooth bar placed, with the gap sealed by silicone glue."
            },
            {
              "kind": "anesthesia",
              "note": "Fiber-transducer BALB/c mice: 1.5% isoflurane in air (~0.5 L/min), reduced to 0.75% during imaging."
            },
            {
              "kind": "surgery",
              "note": "Fiber-transducer mice: hair removed; skull thinned from 1–3 mm posterior to bregma, 8 mm wide, centered on the superior sagittal sinus."
            },
            {
              "kind": "other",
              "note": "Fiber-transducer mice, cortical imaging: cephalic-fixation holder, ventilated respirator mask, ultrasound gel, and polymeric film. Coronal imaging: body fixed and immersed in a temperature-regulated water tank, with silicone sealant at the head–mask gap. Recovery on a heating pad afterward."
            },
            {
              "kind": "surgery",
              "note": "PanoPACT: ~8 mm diameter portion of parietal bone removed without damaging the dura; scalp sutured without replacement."
            },
            {
              "kind": "other",
              "note": "PanoPACT: low-dose mannitol to alleviate brain swelling; brain centered in the array, with the mask–nose interface sealed by parafilm."
            },
            {
              "kind": "other",
              "note": "Human participants: post-hemicraniectomy patients. D2O acoustic coupling medium; distilled water applied on a tensioned PVC film supporting the head; press-fit finger head holder with fasteners; height-adjustable bed."
            }
          ],
          "note": "Preparation by regime: transgenic GCaMP mice imaged through intact skin and skull; rats anesthetized, with scalp opened and skull thinned for anatomy or scalp removed over an intact skull for functional imaging; fiber-transducer mice anesthetized with skull thinning; PanoPACT animals with partial parietal bone removal and scalp closure; post-hemicraniectomy human participants with D2O and water coupling and a film/finger head support."
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          "note": "The conditional depth-contact model adds electrode radius to LFP spread and uses twice that spread as a resolution proxy. Applied to cylindrical RNS contacts, it remains an unvalidated extrapolation rather than a measured depth-electrode discrimination threshold. Under an explicit 2-SD spatial-spread criterion for distinguishing two sources, the resolution proxy is twice the standard deviation of the recording spatial spread. This is a model assumption, not a measured discrimination limit. RNS depth and cortical strip leads are 1.27 mm in diameter with four platinum/iridium electrodes of 0.079 cm2 surface area. A macro contact's spread was proposed to equal the LFP spread (about 0.5 mm) plus the electrode radius, a relationship the source says still needs experiments with electrodes of varying size; for a 1.27 mm diameter depth contact (radius 0.635 mm) this gives an SD of about 1.135 mm, or 2.27 mm at 2 SD. The measured spread of a 2.3 mm diameter macro contact on the cortical surface in macaque V1 is an SD of about 1.5 mm, or about 3 mm at 2 SD. Electrodes sit 3.5 mm or 10 mm apart along a lead, the sampling interval.",
          "endpoint": "two_source_separation",
          "operating_points": [
            {
              "label": "Linear spread model, 1.27 mm diameter depth contact",
              "min": 0.00227,
              "max": 0.00227,
              "note": "2 x (LFP spread about 0.5 mm + contact radius 0.635 mm); a proposed model awaiting experimental verification.",
              "endpoint": "two_source_separation"
            },
            {
              "label": "Measured spread of a 2.3 mm macro contact (macaque V1 surface recording)",
              "min": 0.003,
              "max": 0.003,
              "note": "SD about 1.5 mm, 2 SD about 3 mm.",
              "endpoint": "two_source_separation"
            },
            {
              "label": "Electrode spacing, depth lead DL-330-3.5",
              "min": 0.0035,
              "max": 0.0035,
              "note": "3.5 mm; a sampling interval, not a resolution.",
              "endpoint": "sampling"
            },
            {
              "label": "Electrode spacing, depth lead DL-330-10 and cortical strip leads",
              "min": 0.01,
              "max": 0.01,
              "note": "10 mm.",
              "endpoint": "sampling"
            }
          ]
        },
        "node": "01a16a3a-621c-7882-afdf-e2bb82b2de6f",
        "sources": [
          {
            "node": "01a0547d-626c-7811-8cb0-1ab533d309fb",
            "kind": "doi",
            "id": "10.1038/s41593-018-0108-2",
            "url": "https://doi.org/10.1038/s41593-018-0108-2"
          },
          {
            "node": "01a0a01f-0dd2-7273-9a7f-760324822018",
            "kind": "url",
            "id": "https://www.neuropace.com/wp-content/uploads/2021/02/neuropace-rns-system-manual-320.pdf",
            "url": "https://www.neuropace.com/wp-content/uploads/2021/02/neuropace-rns-system-manual-320.pdf"
          },
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            "node": "01a0abbb-ce8a-7851-bac8-587444e8d878",
            "kind": "doi",
            "id": "10.1523/jneurosci.2917-18.2019",
            "url": "https://doi.org/10.1523/jneurosci.2917-18.2019"
          },
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            "kind": "doi",
            "id": "10.1007/s00701-017-3242-9",
            "url": "https://doi.org/10.1007/s00701-017-3242-9"
          },
          {
            "node": "01a15d4e-33b8-7511-a49a-3bd217f55436",
            "kind": "url",
            "id": "https://www.accessdata.fda.gov/cdrh_docs/pdf10/P100026B.pdf",
            "url": "https://www.accessdata.fda.gov/cdrh_docs/pdf10/P100026B.pdf"
          }
        ]
      },
      "temporal_resolution_s": {
        "state": "known",
        "value": {
          "min": 0.003,
          "max": 0.003,
          "unit": "s",
          "note": "The RNS neurostimulator delivers stimulation pulses at a programmable frequency of 1 to 333 Hz, so the shortest interval between successive stimulation pulses is 1/333 Hz, about 3 ms. On the recording side, electrocorticographic signals are monitored through four differential amplifiers at a 250 Hz sampling rate, a 4 ms sample interval. Pulse widths are 40-1000 microseconds.",
          "endpoint": "inter_pulse_interval",
          "operating_points": [
            {
              "label": "Stimulation at the 333 Hz maximum frequency",
              "min": 0.003,
              "max": 0.003,
              "note": "1/333 Hz, about 3 ms.",
              "endpoint": "inter_pulse_interval"
            },
            {
              "label": "Stimulation at the 1 Hz minimum frequency",
              "min": 1.0,
              "max": 1.0,
              "note": "1/1 Hz.",
              "endpoint": "inter_pulse_interval"
            },
            {
              "label": "ECoG recording at 250 Hz sampling",
              "min": 0.004,
              "max": 0.004,
              "note": "1/250 Hz = 4 ms.",
              "endpoint": "sample_interval"
            },
            {
              "label": "Programmable pulse width",
              "min": 0.00004,
              "max": 0.001,
              "note": "40-1000 microseconds.",
              "endpoint": "pulse_width"
            }
          ]
        },
        "node": "01a15d54-9544-7380-82f8-cc6f1b7a7101",
        "sources": [
          {
            "node": "01a0c16c-68ac-7ad1-8da8-a36d2b6c5039",
            "kind": "url",
            "id": "https://aesnet.org/abstractslisting/clinical-research-use-of-the-neuropace%C2%AE-rns%C2%AE-system",
            "url": "https://aesnet.org/abstractslisting/clinical-research-use-of-the-neuropace%C2%AE-rns%C2%AE-system"
          },
          {
            "node": "01a15d4e-33b8-7511-a49a-3bd217f55436",
            "kind": "url",
            "id": "https://www.accessdata.fda.gov/cdrh_docs/pdf10/P100026B.pdf",
            "url": "https://www.accessdata.fda.gov/cdrh_docs/pdf10/P100026B.pdf"
          }
        ]
      },
      "field_of_view_m3": {
        "state": "known",
        "value": {
          "min": 1.1e-7,
          "max": 2.208e-7,
          "unit": "m3",
          "note": "Illustrative grey-matter sensing model for one or two four-contact leads. Multiplying the study per-contact means by four or eight gives 1.1e-7–2.208e-7 m³. The model assumes every contact lies in grey matter, the RNS contacts have the same mean per-contact sampling volume as the studied implants, and the sensing regions do not overlap. The per-contact means come from 2.5 mm-radius sampling spheres for depth contacts and hemispheres for subdural contacts, intersected with segmented grey matter. The listed SDs are the study per-contact SDs multiplied by the contact count; they do not estimate variability of actual lead-level volumes.",
          "endpoint": "sensing_envelope",
          "operating_points": [
            {
              "label": "Depth-type, 1 lead (4 contacts)",
              "min": 1.1e-7,
              "max": 1.1e-7,
              "note": "1.100×10^-7 m³, SD 1.56×10^-8 m³.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "Depth-type, 2 leads (8 contacts)",
              "min": 2.2e-7,
              "max": 2.2e-7,
              "note": "2.200×10^-7 m³, SD 3.12×10^-8 m³.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "Subdural-strip-type, 1 lead (4 contacts)",
              "min": 1.104e-7,
              "max": 1.104e-7,
              "note": "1.104×10^-7 m³, SD 1.88×10^-8 m³.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "Subdural-strip-type, 2 leads (8 contacts)",
              "min": 2.208e-7,
              "max": 2.208e-7,
              "note": "2.208×10^-7 m³, SD 3.76×10^-8 m³.",
              "endpoint": "sensing_envelope"
            }
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        "sources": [
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            "node": "01a0b266-3f4a-7781-a45f-03ebf38739ee",
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            "node": "01a0c5b6-3dcb-7df1-ae0b-3f0b21f7fb5b",
            "kind": "doi",
            "id": "10.3389/fneur.2021.669406",
            "url": "https://doi.org/10.3389/fneur.2021.669406"
          }
        ]
      },
      "field_of_view_neurons": {
        "state": "incomplete"
      },
      "measurand": {
        "state": "known",
        "value": {
          "measurands": [
            "intracranial ECoG brain activity"
          ],
          "note": "RNS records intracranial ECoG differentially between adjacent contacts and delivers electrical stimulation to brain tissue at the seizure focus—hippocampal or neocortical, depending on lead placement."
        },
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            "kind": "doi",
            "id": "10.1111/epi.12534",
            "url": "https://doi.org/10.1111/epi.12534"
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            "kind": "doi",
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            "id": "10.3389/fdata.2022.840508",
            "url": "https://doi.org/10.3389/fdata.2022.840508"
          }
        ]
      },
      "stimulation": {
        "state": "known",
        "value": {
          "stimuli": [
            "electrical stimulation"
          ],
          "note": "RNS records intracranial ECoG differentially between adjacent contacts and delivers electrical stimulation to brain tissue at the seizure focus—hippocampal or neocortical, depending on lead placement."
        },
        "node": "01a0d3b8-46cd-71e2-8438-56ac65219405",
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            "url": "https://doi.org/10.3389/fdata.2022.840508"
          }
        ]
      },
      "destructiveness": {
        "state": "known",
        "value": {
          "kind": "minimally_destructive",
          "note": "Cranial implantation of the neurostimulator and leads causes incidental, local tissue injury (soft-tissue infection, hemorrhage in 2.0-2.7%); stimulation pulses themselves produce no excess serious adverse events."
        },
        "node": "01a0aba3-e812-7d20-aed0-7fafb94b31dc",
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        ]
      },
      "preparation": {
        "state": "known",
        "value": {
          "steps": [
            {
              "kind": "surgery",
              "note": "Implantation of a skull-mounted neurostimulator with electrodes placed directly into the seizure focus or foci."
            },
            {
              "kind": "other",
              "note": "Prior localization of one or two seizure foci by standard diagnostic testing; the pivotal trial enrolled adults 18-70 with at least three disabling seizures per month despite at least two antiseizure-drug trials."
            },
            {
              "kind": "other",
              "note": "A post-implantation stabilization period of the first four weeks, with sensing and recording enabled and stimulation disabled."
            }
          ],
          "note": "Preparation includes implant surgery and localization of the seizure foci. The pivotal trial also specified patient-eligibility criteria and a four-week sensing-only stabilization interval before stimulation."
        },
        "node": "01a16b37-20af-71b0-a1aa-24de2c2db4c0",
        "sources": [
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            "url": "https://doi.org/10.1038/s43856-023-00401-x"
          }
        ]
      },
      "cost": {
        "state": "known",
        "items": [
          {
            "value": {
              "kind": "procedure",
              "currency": "USD",
              "amount_min": 1750.0,
              "year": 2026,
              "label": "Medicare professional payment for RNS generator insertion, CPT 61889, non-QP"
            },
            "node": "01a07401-f29e-7270-96b7-1fa1622395ab",
            "sources": [
              {
                "node": "01a073fb-fb36-7891-9bed-c3cfb74168fa",
                "kind": "url",
                "id": "https://www.neuropace.com/wp-content/uploads/2026/01/NP_Neurosurgery_Coding_Guide.pdf",
                "url": "https://www.neuropace.com/wp-content/uploads/2026/01/NP_Neurosurgery_Coding_Guide.pdf"
              }
            ]
          },
          {
            "value": {
              "kind": "procedure",
              "currency": "USD",
              "amount_min": 837.0,
              "year": 2026,
              "label": "Medicare professional payment for RNS generator revision/replacement, CPT 61891, non-QP"
            },
            "node": "01a07402-2b31-7063-aa60-e06fb631bff4",
            "sources": [
              {
                "node": "01a073fb-fb36-7891-9bed-c3cfb74168fa",
                "kind": "url",
                "id": "https://www.neuropace.com/wp-content/uploads/2026/01/NP_Neurosurgery_Coding_Guide.pdf",
                "url": "https://www.neuropace.com/wp-content/uploads/2026/01/NP_Neurosurgery_Coding_Guide.pdf"
              }
            ]
          },
          {
            "value": {
              "kind": "instrument",
              "currency": "USD",
              "amount_min": 37600.0,
              "amount_max": 37600.0,
              "year": 2017,
              "label": "VA purchase order to NeuroPace Inc. for a neurostimulator and surgical implant leads, signed March 30, 2017"
            },
            "node": "01a0e175-1541-7c71-9ec9-fd42148aae8f",
            "sources": [
              {
                "node": "01a0e174-3561-7e52-bd21-71b54c68011b",
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              }
            ]
          }
        ]
      },
      "theoretical": {
        "description": {
          "state": "known",
          "value": {
            "text": "Recording: assuming two sources are distinguishable at 2 SDs of the recording's spatial spread, the finest case is microelectrode local field potential recording in primary visual cortex, whose cortical spread has an SD below about 0.5 mm, so 2 SD is below about 1 mm; this is a spread-based proxy, not a measured discrimination limit, and in auditory cortex the LFP spread extends up to several millimetres. A macro contact's spread was proposed to equal the LFP spread plus the electrode radius, growing linearly with electrode size, a model proposed subject to experimental verification; a 2.3 mm surface electrode has an SD of about 1.5 mm (2 SD about 3 mm). Stimulation: in patients, DBS-evoked local responses, which most likely reflect direct nonsynaptic activation of local neuronal elements, have a mean absolute refractory period of 0.56 ms and recover fully by 2.94 ms; fast corticospinal axons have absolute refractory periods of 0.82 ms at high and 1.47 ms at moderate intensity, with complete D-wave recovery by 4 ms."
          },
          "node": "01a16b69-b93c-7a83-a76c-074f24dcfd59",
          "sources": [
            {
              "node": "01a0abbb-ce8a-7851-bac8-587444e8d878",
              "kind": "doi",
              "id": "10.1523/jneurosci.2917-18.2019",
              "url": "https://doi.org/10.1523/jneurosci.2917-18.2019"
            },
            {
              "node": "01a0e804-89a4-7601-8a09-9ffa5ea657ac",
              "kind": "doi",
              "id": "10.1002/acn3.51275",
              "url": "https://doi.org/10.1002/acn3.51275"
            },
            {
              "node": "01a0e806-80e3-7503-a0be-43640e59d508",
              "kind": "doi",
              "id": "10.1016/j.clinph.2004.03.016",
              "url": "https://doi.org/10.1016/j.clinph.2004.03.016"
            },
            {
              "node": "01a0e806-8bbb-7880-be4e-a2b8b12fb328",
              "kind": "doi",
              "id": "10.1016/s1388-2457(01)00461-8",
              "url": "https://doi.org/10.1016/s1388-2457(01)00461-8"
            }
          ]
        },
        "spatial_resolution_m": {
          "state": "known",
          "value": {
            "max": 0.001,
            "unit": "m",
            "note": "Under an explicit 2-SD spatial-spread criterion for distinguishing two sources, the resolution proxy is twice the standard deviation of the recording spatial spread. This is a model assumption, not a measured discrimination limit. In-principle case: microelectrode LFP in primary visual cortex (V1). Its cortical spread, estimated as a spatial weighting function that depends mainly on electrode size, impedance and location and on tissue filtering, and confirmed by other methods, has SD < ~0.5 mm, so 2 SD < ~1 mm. With analogous methods in auditory cortex, LFP spread is much larger than MUA, extending up to several millimeters. Proposed from the ECoG comparison: a macro contact's spread ≈ LFP spread (~0.5 mm) + electrode radius (~1.15 mm), increasing linearly with electrode size. The linear macro-contact model was proposed subject to experimental verification with electrodes of varying size. Context: ECoG spread SD ~1.5 mm (2 SD ~3 mm) for a 2.3 mm diameter electrode, ~3× the LFP spread.",
            "endpoint": "two_source_separation",
            "operating_points": [
              {
                "label": "V1 microelectrode LFP spread-based proxy",
                "max": 0.001,
                "note": "2 × SD, from SD < ~0.5 mm of V1 LFP cortical spread. Upper bound only.",
                "endpoint": "two_source_separation"
              }
            ]
          },
          "node": "01a16a3b-655a-7173-a5f4-7fdd84742d99",
          "sources": [
            {
              "node": "01a0abbb-ce8a-7851-bac8-587444e8d878",
              "kind": "doi",
              "id": "10.1523/jneurosci.2917-18.2019",
              "url": "https://doi.org/10.1523/jneurosci.2917-18.2019"
            }
          ]
        },
        "temporal_resolution_s": {
          "state": "known",
          "value": {
            "min": 0.00056,
            "max": 0.00056,
            "unit": "s",
            "note": "Refractory intervals for DBS-evoked local responses and corticospinal D-wave axons in human patients, from the DBS absolute refractory period to complete D-wave recovery. The DBS local response most likely represents nonsynaptic, direct activation of local neuronal elements.",
            "endpoint": "inter_pulse_interval",
            "operating_points": [
              {
                "label": "Neural absolute refractory period (measured in DBS-evoked responses)",
                "min": 0.00056,
                "max": 0.00056,
                "note": "Mean 0.00056 s (SD 0.00008 s); 17 human patients; intraoperative DBS recording at subthalamic, pallidal and thalamic targets. Defined as the first interstimulus interval among three consecutive paired-pulse ratios <0.2.",
                "endpoint": "inter_pulse_interval"
              },
              {
                "label": "Neural relative refractory period: full recovery (measured in DBS-evoked responses)",
                "min": 0.00294,
                "max": 0.00294,
                "note": "Mean 0.00294 s (SD 0.00105 s); 17 human patients; intraoperative DBS recording at subthalamic, pallidal and thalamic targets. Defined as the first interstimulus interval among three consecutive paired-pulse ratios >0.98.",
                "endpoint": "inter_pulse_interval"
              },
              {
                "label": "Corticospinal D wave: absolute refractory period at high intensity",
                "min": 0.00082,
                "max": 0.00082,
                "note": "Mean 0.00082 s; 14 human patients undergoing surgical correction of spinal deformities; epidural D-wave recording with paired transcranial electrical stimulation under anesthesia.",
                "endpoint": "inter_pulse_interval"
              },
              {
                "label": "Corticospinal D wave: absolute refractory period at moderate intensity",
                "min": 0.00147,
                "max": 0.00147,
                "note": "Mean 0.00147 s; 14 human patients undergoing surgical correction of spinal deformities; epidural D-wave recording with paired transcranial electrical stimulation under anesthesia.",
                "endpoint": "inter_pulse_interval"
              },
              {
                "label": "Corticospinal D wave: complete recovery",
                "min": 0.004,
                "max": 0.004,
                "note": "0.004 s; human patients at anesthetic depths suppressing indirect activity; epidural D-wave recording with two equal transcranial electrical stimuli. Both D2 amplitude and conduction time recovered completely.",
                "endpoint": "inter_pulse_interval"
              }
            ]
          },
          "node": "01a16d75-aa7c-75c2-9092-6227109eb2e8",
          "sources": [
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      "slug": "seeg",
      "name": "sEEG",
      "group": {
        "id": "electrophysiology",
        "name": "Electrophysiology"
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      "mode": "both",
      "core": true,
      "summary": {
        "value": "Stereo-EEG is an invasive method that implants thin, cylindrical electrodes into the brain with stereotactic guidance, reaching deep, folded and both-sided regions without an open craniotomy, sometimes alongside surface grids. Each electrode records the summed electrical fields (local field potentials) of nearby neurons, and a high-frequency broadband part of that signal correlates with the averaged firing of thousands of nearby neurons. Before surgery for drug-resistant epilepsy it helps locate where seizures start and map nearby function, and the electrodes can also deliver constant-current, charge-balanced electrical pulses.",
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        "value": {
          "text": "Stereo-EEG (sEEG) is invasive intracranial EEG that uses stereotactically implanted, thin cylindrical depth electrodes to penetrate the brain and reach deep, sulcal and bilateral sites without open craniotomy, either alone or combined with subdural surface grids. Each electrode records the summed local field potentials of the neuronal population near its contacts; oscillatory-band activity in that signal is accompanied by high-frequency broadband activity that correlates with the averaged spiking of thousands of nearby neurons. Clinically, sEEG is used presurgically in drug-resistant epilepsy to localize the epileptogenic zone and map related functional cortex, and implanted electrodes can also deliver constant-current, charge-balanced stimulation pulses to the targeted population."
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        "value": {
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          "unit": "m",
          "note": "The depth-contact calculation conditionally applies the surface-contact spread model to cylindrical sEEG contacts; it is not an experimentally validated depth-electrode spread measurement. Under an explicit 2-SD spatial-spread criterion for distinguishing two sources, the resolution proxy is twice the standard deviation of the recording spatial spread. This is a model assumption, not a measured discrimination limit. sEEG contacts are cylinders about 0.8-1 mm in diameter and 2 mm long. A macro contact's spread was proposed to equal the LFP spread (about 0.5 mm) plus the electrode radius, a relationship the source says still needs experiments with electrodes of varying size; for a 0.8-1 mm diameter contact this gives an SD of about 0.9-1 mm, or 1.8-2 mm at 2 SD. The measured spread of a larger, 2.3 mm diameter macro contact on the cortical surface in macaque V1 is an SD of about 1.5 mm, or about 3 mm at 2 SD, which bounds the range above. Contacts on one lead sit at a 3.5 mm centre-to-centre pitch (2 mm contacts with 1.5 mm inter-contact distance), the sampling interval along the lead.",
          "endpoint": "two_source_separation",
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            {
              "label": "Linear spread model, 0.8-1 mm diameter sEEG contact",
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              "note": "2 x (LFP spread about 0.5 mm + contact radius 0.4-0.5 mm); a proposed model awaiting experimental verification.",
              "endpoint": "two_source_separation"
            },
            {
              "label": "Measured spread of a 2.3 mm macro contact (macaque V1 surface recording)",
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              "note": "SD about 1.5 mm, 2 SD about 3 mm.",
              "endpoint": "two_source_separation"
            },
            {
              "label": "Contact pitch along a clinical depth lead",
              "min": 0.0035,
              "max": 0.0035,
              "note": "2 mm contact length + 1.5 mm inter-contact distance = 3.5 mm centre-to-centre; a sampling interval, not a resolution.",
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            "kind": "doi",
            "id": "10.1523/jneurosci.2917-18.2019",
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            "id": "10.1007/s00701-017-3242-9",
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        "value": {
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          "unit": "s",
          "note": "Reciprocal-frequency timing estimate: assume the highest neural frequency detected above noise defines an effective temporal bandwidth, and take recoverable timing as dt ≈ 1/B. This is an assumed proxy, not measured two-event discrimination. Recoverable timing is taken as dt ≈ 1/B, where B is the upper edge of the highest neural-signal band a recording is shown to capture; a sampling interval is not the resolution. Intracranial EEG from depth macroelectrodes has been shown to capture ripples (80-250 Hz) and fast ripples (250-500 Hz), which gives conditional reciprocal-frequency estimates of about 4 ms and 2 ms respectively. Labelled limits: the fast-ripple recordings used 2000 Hz sampling (Nyquist 1000 Hz). Other sEEG recordings used 500 Hz sampling (Nyquist 250 Hz, which cannot contain the 250-500 Hz band) or 1000 Hz sampling (Nyquist 500 Hz), with no band shown for them.",
          "endpoint": "recoverable_timing",
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            {
              "label": "Ripples (80-250 Hz), B = 250 Hz",
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              "max": 0.004,
              "note": "dt ~ 1/250 Hz = 4 ms; recorded from depth macroelectrodes at 2000 Hz sampling.",
              "endpoint": "recoverable_timing"
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            {
              "label": "Fast ripples (250-500 Hz), B = 500 Hz",
              "min": 0.002,
              "max": 0.002,
              "note": "dt ~ 1/500 Hz = 2 ms; recorded from depth macroelectrodes at 2000 Hz sampling.",
              "endpoint": "recoverable_timing"
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            "id": "10.1073/pnas.2017401118",
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            "id": "10.1038/s41598-026-50113-0",
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            "id": "10.1093/brain/awn351",
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      "field_of_view_m3": {
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        "value": {
          "min": 1.861e-6,
          "max": 5.646e-6,
          "unit": "m3",
          "note": "Across 10 SEEG subjects, modeled implanted-montage gray-matter coverage was 1.861–5.646×10⁻⁶ m³. Each contact was modeled as a 2.5 mm-radius sphere; its recording-volume mask was overlaid with FreeSurfer gray matter—cerebral cortex, amygdala, and hippocampus—and overlapping voxels were summed.",
          "endpoint": "sensing_envelope",
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              "min": 3.518e-6,
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              "note": "Modeled total gray-matter recording volume.",
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              "note": "Modeled total gray-matter recording volume.",
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              "min": 5.646e-6,
              "max": 5.646e-6,
              "note": "Modeled total gray-matter recording volume.",
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              "max": 2.581e-6,
              "note": "Modeled total gray-matter recording volume.",
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            {
              "label": "SEEG subject 5",
              "min": 4.427e-6,
              "max": 4.427e-6,
              "note": "Modeled total gray-matter recording volume.",
              "endpoint": "sensing_envelope"
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            {
              "label": "SEEG subject 6",
              "min": 3.099e-6,
              "max": 3.099e-6,
              "note": "Modeled total gray-matter recording volume.",
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              "label": "SEEG subject 7",
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              "max": 4.941e-6,
              "note": "Modeled total gray-matter recording volume.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "SEEG subject 8",
              "min": 3.58e-6,
              "max": 3.58e-6,
              "note": "Modeled total gray-matter recording volume.",
              "endpoint": "sensing_envelope"
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            {
              "label": "SEEG subject 9",
              "min": 1.861e-6,
              "max": 1.861e-6,
              "note": "Modeled total gray-matter recording volume.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "SEEG subject 10",
              "min": 2.822e-6,
              "max": 2.822e-6,
              "note": "Modeled total gray-matter recording volume.",
              "endpoint": "sensing_envelope"
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            "id": "10.3389/fneur.2021.669406",
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        "state": "incomplete"
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        "state": "known",
        "value": {
          "measurands": [
            "local field potential",
            "high-frequency broadband activity"
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          "note": "Records the summed local field potentials of the neuronal population near each contact; high-frequency broadband activity correlates with the averaged spiking of thousands of nearby neurons."
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      "stimulation": {
        "state": "known",
        "value": {
          "stimuli": [
            "electrical pulses delivered via implanted intracranial electrodes to the targeted neuronal population"
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          "note": "Implanted intracranial electrodes (iEEG, including sEEG depth electrodes) can deliver electrical pulses to the specific neuronal population they target, in addition to recording signals from it."
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        "value": {
          "kind": "minimally_destructive",
          "note": "Depth-electrode tracts cause incidental local injury; reported complication rates are low to modest: 1.3-8.0% surgical/adverse events, hemorrhage 1.0-3.9%, infection 0.3-0.8%, mortality 0.2-0.3%; some series report morbidity up to 7-7.5%."
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        "value": {
          "steps": [
            {
              "kind": "surgery",
              "note": "Stereotactic depth-electrode implantation via twist-drill holes (bolts require sufficient skull thickness), by the Talairach method along orthogonal or oblique trajectories, sometimes combined with craniotomy for subdural grids."
            },
            {
              "kind": "anesthesia",
              "note": "General anesthesia in the operating room during implantation."
            },
            {
              "kind": "other",
              "note": "Pre-operative MRI for stereotactic planning and post-implant CT (fused to MRI) to confirm electrode placement and rule out hemorrhage; wired inpatient monitoring continues for days to weeks until seizures are captured, then electrodes are surgically removed."
            }
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          "note": "Stereotactic surgical implantation under general anesthesia, with imaging-guided planning and verification and multi-day inpatient monitoring before removal."
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      "cost": {
        "state": "known",
        "items": [
          {
            "value": {
              "kind": "procedure",
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              "amount_min": 106291.0,
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                "url": "https://www.utsouthwestern.edu/research/core-facilities/quantitative-light-microscopy/equipment-fees-and-services/"
              }
            ]
          }
        ]
      },
      "theoretical": {
        "description": {
          "state": "incomplete"
        },
        "spatial_resolution_m": {
          "state": "incomplete"
        },
        "temporal_resolution_s": {
          "state": "incomplete"
        },
        "field_of_view_m3": {
          "state": "incomplete"
        },
        "field_of_view_neurons": {
          "state": "incomplete"
        }
      }
    },
    {
      "slug": "tavns",
      "name": "taVNS",
      "group": {
        "id": "stim-noninvasive",
        "name": "Non-invasive write"
      },
      "mode": "write",
      "core": false,
      "summary": null,
      "row_node": "01a1664a-f3cc-7713-b998-72e53a8e4be5",
      "description": {
        "state": "known",
        "value": {
          "text": "Auricular transcutaneous vagus-nerve stimulation delivers electrical current through skin-surface electrodes at the cymba conchae, concha or tragus, targeting the auricular branch of the vagus nerve. Reported fMRI responses include the ipsilateral nucleus tractus solitarius through vagal projections. Examples use 10 or 25 Hz stimulation; one 10 Hz protocol used 0.3 ms pulses. A dissection of 14 ears from seven cadavers found vagal-branch innervation at the cymba conchae in every specimen. This anatomical pattern describes innervation, not the fraction of fibres recruited by stimulation."
        },
        "node": "01a165fe-c574-7b50-9c23-f477d64ad5f1",
        "sources": [
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            "node": "01a05915-7c46-7933-862d-44ac0a33410c",
            "kind": "doi",
            "id": "10.1007/s40473-014-0010-5",
            "url": "https://doi.org/10.1007/s40473-014-0010-5"
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          {
            "node": "01a05915-a8fd-7991-9f89-3479f88db870",
            "kind": "doi",
            "id": "10.3389/fnhum.2020.568051",
            "url": "https://doi.org/10.3389/fnhum.2020.568051"
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          {
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            "node": "01a05915-feec-7a90-aa8a-60fcbcf51912",
            "kind": "doi",
            "id": "10.1038/s41598-022-25864-1",
            "url": "https://doi.org/10.1038/s41598-022-25864-1"
          },
          {
            "node": "01a14cb6-456b-7d52-af7f-5cf91c74ed10",
            "kind": "doi",
            "id": "10.1002/ca.1089",
            "url": "https://doi.org/10.1002/ca.1089"
          }
        ]
      },
      "spatial_resolution_m": {
        "state": "known",
        "value": {
          "min": 0.008,
          "max": 0.008,
          "unit": "m",
          "note": "Diameter of the round metal stimulating-electrode contact used on the tragus."
        },
        "node": "01a0ba77-35d1-70b2-bde7-53876990c35f",
        "sources": [
          {
            "node": "01a0b265-4de9-7371-ab69-889c0c235dfb",
            "kind": "doi",
            "id": "10.3791/58984",
            "url": "https://doi.org/10.3791/58984"
          }
        ]
      },
      "temporal_resolution_s": {
        "state": "known",
        "value": {
          "min": 0.04,
          "max": 0.1,
          "unit": "s",
          "note": "Continuous-frequency stimulation pulse intervals span 0.04–0.10 s. The 10 Hz protocol had a 0.3 ms pulse width, not a pulse interval. The 2–100 Hz protocol was burst-mode; pulse spacing within bursts is not given.",
          "operating_points": [
            {
              "label": "25 Hz — tragus; left concha on the inner side of the tragus",
              "min": 0.04,
              "max": 0.04,
              "note": "Interval between successive stimulation pulses."
            },
            {
              "label": "10 Hz — ear site not given",
              "min": 0.1,
              "max": 0.1,
              "note": "Interval between successive stimulation pulses."
            }
          ]
        },
        "node": "01a0e5b9-8536-7422-adcb-0942e645acfd",
        "sources": [
          {
            "node": "01a05915-d4bc-74b1-ba58-e301c62d7324",
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            "id": "10.3389/fnins.2020.00284",
            "url": "https://doi.org/10.3389/fnins.2020.00284"
          }
        ]
      },
      "field_of_view_m3": {
        "state": "incomplete"
      },
      "field_of_view_neurons": {
        "state": "incomplete"
      },
      "measurand": {
        "state": "unknown",
        "value": {
          "reason": "taVNS has no measurand of its own; it delivers current through skin-surface electrodes on the ear (cymba conchae, concha, or tragus) rather than measuring or recording a quantity."
        },
        "node": "01a0e5bf-d5f4-7631-8bcb-6f8600556c1c",
        "sources": [
          {
            "node": "01a05915-7c46-7933-862d-44ac0a33410c",
            "kind": "doi",
            "id": "10.1007/s40473-014-0010-5",
            "url": "https://doi.org/10.1007/s40473-014-0010-5"
          },
          {
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            "kind": "doi",
            "id": "10.3389/fnhum.2020.568051",
            "url": "https://doi.org/10.3389/fnhum.2020.568051"
          },
          {
            "node": "01a05915-d4bc-74b1-ba58-e301c62d7324",
            "kind": "doi",
            "id": "10.3389/fnins.2020.00284",
            "url": "https://doi.org/10.3389/fnins.2020.00284"
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          {
            "node": "01a05915-feec-7a90-aa8a-60fcbcf51912",
            "kind": "doi",
            "id": "10.1038/s41598-022-25864-1",
            "url": "https://doi.org/10.1038/s41598-022-25864-1"
          },
          {
            "node": "01a0b2c5-cf70-77e1-b11b-eefc704868b8",
            "kind": "doi",
            "id": "10.1016/j.brs.2018.06.003",
            "url": "https://doi.org/10.1016/j.brs.2018.06.003"
          }
        ]
      },
      "stimulation": {
        "state": "known",
        "value": {
          "stimuli": [
            "cutaneous electrical pulses"
          ],
          "note": "Skin-surface electrodes at the cymba conchae, concha or tragus deliver electrical current targeting the auricular branch of the vagus nerve."
        },
        "node": "01a1662b-3b67-73d0-a4fe-53eff27f8959",
        "sources": [
          {
            "node": "01a05915-7c46-7933-862d-44ac0a33410c",
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            "url": "https://doi.org/10.1007/s40473-014-0010-5"
          },
          {
            "node": "01a05915-a8fd-7991-9f89-3479f88db870",
            "kind": "doi",
            "id": "10.3389/fnhum.2020.568051",
            "url": "https://doi.org/10.3389/fnhum.2020.568051"
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          {
            "node": "01a05915-d4bc-74b1-ba58-e301c62d7324",
            "kind": "doi",
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            "kind": "doi",
            "id": "10.1038/s41598-022-25864-1",
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          },
          {
            "node": "01a14cb6-456b-7d52-af7f-5cf91c74ed10",
            "kind": "doi",
            "id": "10.1002/ca.1089",
            "url": "https://doi.org/10.1002/ca.1089"
          }
        ]
      },
      "destructiveness": {
        "state": "known",
        "value": {
          "kind": "non_destructive",
          "note": "taVNS uses non-invasive skin-surface ear electrodes and requires no surgery; no tissue damage is reported."
        },
        "node": "01a0b774-6411-7613-a66d-317346dcdff2",
        "sources": [
          {
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          {
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            "kind": "doi",
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            "url": "https://doi.org/10.3389/fnhum.2020.568051"
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          {
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            "id": "10.1038/s41598-022-25864-1",
            "url": "https://doi.org/10.1038/s41598-022-25864-1"
          }
        ]
      },
      "preparation": {
        "state": "known",
        "value": {
          "steps": [
            {
              "kind": "other",
              "note": "Placement of skin-surface electrodes on the ear (cymba conchae, concha, or tragus) over auricular-branch-of-vagus-nerve-innervated skin."
            }
          ],
          "note": "Non-invasive; no surgery, anesthesia, or genetic engineering is required, and the electrodes can be self-administered."
        },
        "node": "01a0aba5-cb23-7413-849f-89c1145ccf66",
        "sources": [
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            "node": "01a05915-7c46-7933-862d-44ac0a33410c",
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            "kind": "doi",
            "id": "10.1038/s41598-022-25864-1",
            "url": "https://doi.org/10.1038/s41598-022-25864-1"
          }
        ]
      },
      "cost": {
        "state": "known",
        "items": [
          {
            "value": {
              "kind": "instrument",
              "currency": "EUR",
              "amount_min": 700.0,
              "amount_max": 700.0,
              "label": "Nurosym regular listed instrument price — Ireland storefront"
            },
            "node": "01a0c152-9046-7872-b127-3a41e912e553",
            "sources": [
              {
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        ]
      },
      "theoretical": {
        "description": {
          "state": "incomplete"
        },
        "spatial_resolution_m": {
          "state": "incomplete"
        },
        "temporal_resolution_s": {
          "state": "incomplete"
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        "field_of_view_m3": {
          "state": "incomplete"
        },
        "field_of_view_neurons": {
          "state": "incomplete"
        }
      }
    },
    {
      "slug": "tcd",
      "name": "Transcranial Doppler",
      "group": {
        "id": "optical",
        "name": "Optical & ultrasound (in vivo)"
      },
      "mode": "read",
      "core": false,
      "summary": null,
      "row_node": "01a1664f-8bf3-7d80-8cb0-3cb3ccaa5b65",
      "description": {
        "state": "known",
        "value": {
          "text": "Transcranial Doppler is a noninvasive ultrasound study that measures blood-flow velocity in major intracranial arteries. Low-frequency ultrasound at 2 MHz or below passes through relatively thin bone windows to insonate the basal cerebral arteries. Received echoes are processed into a velocity waveform with peak systolic and end-diastolic values. The frequently used transtemporal window can insonate the middle, anterior and posterior cerebral arteries and terminal internal carotid artery."
        },
        "node": "01a16604-6e2a-7281-8183-d0ee35b9bcea",
        "sources": [
          {
            "node": "01a054c1-1bdc-7842-8b8f-f28f4f0fbce1",
            "kind": "doi",
            "id": "10.1155/2013/629378",
            "url": "https://doi.org/10.1155/2013/629378"
          }
        ]
      },
      "spatial_resolution_m": {
        "state": "known",
        "value": {
          "min": 0.005,
          "max": 0.015,
          "unit": "m",
          "note": "Recommended practical TCD sample-volume gate length.",
          "operating_points": [
            {
              "label": "Large gate setting",
              "min": 0.01,
              "max": 0.015,
              "note": "10–15 mm sample volume."
            },
            {
              "label": "Small gate setting",
              "min": 0.005,
              "max": 0.01,
              "note": "5–10 mm spectral gate length."
            }
          ]
        },
        "node": "01a0d348-fc32-7fb3-8afb-82ff7feb48c3",
        "sources": [
          {
            "node": "01a0b28e-d853-7190-81bd-516797c04176",
            "kind": "doi",
            "id": "10.1111/j.1552-6569.2006.00088.x",
            "url": "https://doi.org/10.1111/j.1552-6569.2006.00088.x"
          }
        ]
      },
      "temporal_resolution_s": {
        "state": "known",
        "value": {
          "min": 0.0025,
          "max": 0.004608294930875576,
          "unit": "s",
          "note": "Practical output sampling intervals of the TCD blood-flow velocity waveform. These are shifts between overlapping spectral windows, not the longer window durations.",
          "operating_points": [
            {
              "label": "Illustrative 10 ms window, 75% overlap",
              "min": 0.0025,
              "max": 0.0025,
              "note": "Illustrative configuration (“e.g., 10 ms”): the output interval is the non-overlapping 25% of the 10 ms spectral analysis window, or 2.5 ms."
            },
            {
              "label": "Clinical recording cadence",
              "min": 0.004608294930875576,
              "max": 0.004608294930875576,
              "note": "The explicitly reported shift between overlapping windows was 1/217 s, producing a 217 Hz blood-flow velocity waveform."
            }
          ]
        },
        "node": "01a0d34f-8397-72d2-be6f-b298f1226467",
        "sources": [
          {
            "node": "01a0d34b-58c9-7330-ab25-0c278045546e",
            "kind": "doi",
            "id": "10.1109/jtehm.2020.3011562",
            "url": "https://doi.org/10.1109/jtehm.2020.3011562"
          }
        ]
      },
      "field_of_view_m3": {
        "state": "known",
        "value": {
          "min": 0.000216,
          "max": 0.000216,
          "unit": "m3",
          "note": "Volumetric power Doppler image of major cerebral arteries from participant 1, acquired through the temporal window over a 60 × 60 × 60 mm³ region; box volume = 0.06 m × 0.06 m × 0.06 m = 2.16 × 10⁻⁴ m³ (216 cm³)."
        },
        "node": "01a14f6b-367c-7ff1-990d-38d7543df28a",
        "sources": [
          {
            "node": "01a0d34e-759a-7b31-83e5-11914cf31e6f",
            "kind": "doi",
            "id": "10.1038/s41586-024-07381-5",
            "url": "https://doi.org/10.1038/s41586-024-07381-5"
          }
        ]
      },
      "field_of_view_neurons": {
        "state": "incomplete"
      },
      "measurand": {
        "state": "known",
        "value": {
          "measurands": [
            "cerebral blood-flow velocity"
          ],
          "note": "Reported as a spectral Doppler waveform with peak systolic and end-diastolic velocity values for the basal cerebral arteries (MCA, ACA, PCA, terminal ICA) reached via the transtemporal window."
        },
        "node": "01a0ab8b-737b-73c3-bd58-feeb8f59826c",
        "sources": [
          {
            "node": "01a054c1-1bdc-7842-8b8f-f28f4f0fbce1",
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            "id": "10.1155/2013/629378",
            "url": "https://doi.org/10.1155/2013/629378"
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            "node": "01a054c1-2219-7dd3-8aeb-2e73c2fe75ba",
            "kind": "doi",
            "id": "10.4103/2211-4122.183746",
            "url": "https://doi.org/10.4103/2211-4122.183746"
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        ]
      },
      "stimulation": {
        "state": "incomplete"
      },
      "destructiveness": {
        "state": "known",
        "value": {
          "kind": "non_destructive",
          "note": "Described as a noninvasive ultrasound study: a transducer is placed on the scalp to insonate arteries through existing thin bone windows, with nothing said about entering or damaging tissue."
        },
        "node": "01a0ab8b-9f8a-7e01-965a-0248fbe60241",
        "sources": [
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            "node": "01a054c1-1bdc-7842-8b8f-f28f4f0fbce1",
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            "url": "https://doi.org/10.1155/2013/629378"
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            "kind": "doi",
            "id": "10.4103/2211-4122.183746",
            "url": "https://doi.org/10.4103/2211-4122.183746"
          }
        ]
      },
      "preparation": {
        "state": "known",
        "value": {
          "steps": [],
          "note": "The described TCD examination requires no preparation beyond placing the low-frequency ultrasound transducer on the scalp over an acoustic window and beginning insonation at the stated settings."
        },
        "node": "01a0b7b1-0be9-7a13-8500-4e2825a45afb",
        "sources": [
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            "url": "https://doi.org/10.1155/2013/629378"
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          {
            "node": "01a054c1-2219-7dd3-8aeb-2e73c2fe75ba",
            "kind": "doi",
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            "node": "01a0b28e-d853-7190-81bd-516797c04176",
            "kind": "doi",
            "id": "10.1111/j.1552-6569.2006.00088.x",
            "url": "https://doi.org/10.1111/j.1552-6569.2006.00088.x"
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        ]
      },
      "cost": {
        "state": "known",
        "items": [
          {
            "value": {
              "kind": "procedure",
              "currency": "USD",
              "amount_min": 243.77,
              "year": 2026,
              "label": "Medicare CY2026 OPPS national unadjusted payment rate, transcranial Doppler (CPT 93886)"
            },
            "node": "01a090c5-a889-7510-826a-7f2f12450932",
            "sources": [
              {
                "node": "01a05972-2dc8-7091-9c27-760e9af9e164",
                "kind": "url",
                "id": "https://www.cms.gov/files/zip/july-2026-opps-addendum-b.zip",
                "url": "https://www.cms.gov/files/zip/july-2026-opps-addendum-b.zip"
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            ]
          },
          {
            "value": {
              "kind": "session",
              "currency": "USD",
              "amount_min": 106.81,
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              "label": "Medicare CY2026 OPPS TCD, CPT 93888/93892/93893 (each)"
            },
            "node": "01a06f3a-1dc1-7710-9eb1-5e56352b8350",
            "sources": [
              {
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                "url": "https://www.cms.gov/files/zip/july-2026-opps-addendum-b.zip"
              }
            ]
          }
        ]
      },
      "theoretical": {
        "description": {
          "state": "incomplete"
        },
        "spatial_resolution_m": {
          "state": "incomplete"
        },
        "temporal_resolution_s": {
          "state": "incomplete"
        },
        "field_of_view_m3": {
          "state": "incomplete"
        },
        "field_of_view_neurons": {
          "state": "incomplete"
        }
      }
    },
    {
      "slug": "temporal-interference",
      "name": "Temporal interference",
      "group": {
        "id": "stim-noninvasive",
        "name": "Non-invasive write"
      },
      "mode": "write",
      "core": true,
      "summary": {
        "value": "Temporal interference stimulation is noninvasive deep-brain electrical stimulation through pairs of scalp electrodes. Each pair passes current at a slightly different kilohertz frequency, too fast for neurons to follow; where the currents overlap deep in the brain they produce a slow beat at the difference between the two frequencies. It writes by delivering this beat, which stimulates neurons and modulates brain rhythms and hippocampal activity, while the fast currents do not make neurons fire. At human field strengths, direct stimulation may be too weak, and the effective intensity remains unclear.",
        "node": "01a150f5-954d-7c13-8a58-f95e823d1b1c",
        "sources": [
          {
            "node": "01a05934-eead-72b2-9de0-45ca6e3d2b69",
            "kind": "doi",
            "id": "10.1016/j.cell.2017.05.024",
            "url": "https://doi.org/10.1016/j.cell.2017.05.024"
          },
          {
            "node": "01a05934-fc37-7ea0-a9bd-bd56b2a56c5e",
            "kind": "doi",
            "id": "10.1016/j.neuroimage.2019.116124",
            "url": "https://doi.org/10.1016/j.neuroimage.2019.116124"
          },
          {
            "node": "01a05935-0890-75b1-8676-d8cfbe42d3bb",
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          "text": "Temporal interference stimulation (TI, or transcranial temporal interference stimulation, tTIS) is noninvasive, steerable deep-brain electrical stimulation. Two or more pairs of scalp electrodes deliver currents at slightly different kilohertz frequencies, each too fast for neurons to follow. Where the fields overlap at depth they interfere and produce an envelope that oscillates at the difference between the carrier frequencies, which lies within the range of neural activity: 1 mA at 1.00 kHz with 1 mA at 1.04 kHz gives a 40 Hz envelope, 2.000 with 2.010 kHz gives 10 Hz, and 9.00 with 9.13 kHz at up to 4 mA peak-to-peak per pair gives 130 Hz. The kilohertz carriers do not themselves recruit firing. The envelope is what acts on tissue: it stimulates neurons, modulating neural oscillations and hippocampal activity. At human field strengths, direct stimulation may be too weak, and the effective intensity remains unclear: in finite-element human head models the hippocampal field reaches only about 0.38 V/m, orders of magnitude below the roughly 100 V/m threshold for direct neuronal activation, and mouse head models reach 383 V/m at 0.776 mA. The kilohertz currents avoid the scalp irritation and pain of conventional noninvasive transcranial electrical stimulation."
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            "Multiple slightly offset kHz carrier currents: 1 mA at 1.00 and 1.04 kHz (40 Hz envelope); 2.000 and 2.010 kHz (10 Hz); or up to 4 mA peak-to-peak per pair at 9.00 and 9.13 kHz (130 Hz)."
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          "kind": "non_destructive",
          "note": "TI/tTIS uses scalp electrodes and is not reported to penetrate, lesion, heat, or remove tissue by design. It was generally well tolerated; mild paresthesias, fatigue, and dizziness occurred. Mice showed no neuronal, synaptic, or tissue damage over 28 days."
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              "note": "Place scalp electrodes for human transcranial stimulation."
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              "note": "Ketamine-xylazine anesthesia in the head-fixed mouse demonstration; this is not a requirement of the human scalp protocol."
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            "value": {
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              "year": 2022,
              "label": "VA Soterix interferential stimulator system, obligated 2022"
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            "text": "Spatial: at 2 mA total current, the smallest modelled volume above 0.25 V/m when targeting left motor cortex (the Pareto-optimal four-electrode pattern) corresponds to an idealized sphere-equivalent diameter of at most 0.01675 m. Extent: across all simulated configurations and current ratios at 2 mA, at most 1.3923×10⁻⁴ m³ (139.23 cm³) of brain exceeds 0.25 V/m. Strength: in a quasi-static analysis, the modulation depth of the interfering waveform is equal to or smaller than what conventional transcranial electric stimulation achieves with the same two electrode pairs, so conventional stimulation can give the same or stronger field intensity (tDCS) or modulation (tACS); that modelling comparison found no scenario where interferential stimulation outperformed it. What distinguishes the method is that its kHz carriers are fields the neural membrane's low-pass filtering does not let neural activity follow, while the envelope repeats at a difference frequency within the range of neural activity. Human studies are reported in which interferential stimulation targeted to the hippocampus modulated hippocampal activity and improved episodic memory accuracy in 20 healthy participants (fMRI and behaviour), and theta-burst stimulation of the striatum enhanced striatal activity and motor skill learning."
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          "value": {
            "max": 0.01675,
            "unit": "m",
            "note": "Left motor cortex; ETIfree Pareto-optimal pattern minimizing the Vol_(0.25) column while exceeding 0.25 V/m in the target, at 2 mA total current over four-electrode configurations. Stimulated fractions: g = 0.05% GM = 0.0005 and w = 0.18% WM = 0.0018. V = g·GM + w·WM <= (g + w)·total = 0.0005·1070 + 0.0018·1070 = 0.535 + 1.926 = 2.461 cm³. The diameter, d = (6V/pi)^(1/3) = 0.01675 m, is an idealized sphere-equivalent upper bound.",
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            "note": "Upper bound on human-head-model brain volume with ETIfree above 0.25 V/m at 2 mA total tTIS current, for the union over all simulated electrode configurations and current ratios. Bound: 0.13·WM + 0.017·GM ≤ 0.13·(WM + GM) ≤ 0.13·1071 cm³ = 139.23 cm³ = 1.3923×10⁻⁴ m³.",
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        "value": "Transcranial electrical stimulation (tES) passes a weak electric current between electrodes on the scalp. In tDCS the current is constant, and at 1–2 mA it sets up a cortical field of up to about 0.4–0.8 V/m that shifts neurons' membrane potential below firing threshold, changing their excitability. tACS uses a sinusoidal current aimed at brain oscillations, and tRNS a random-noise current. In 2025 the US Food and Drug Administration approved a home tDCS headset for depression.",
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          "text": "Transcranial electrical stimulation (tES) is a non-invasive brain stimulation technique that passes a weak electric current between two or more scalp electrodes to modulate brain activity. Much of the current is shunted through the scalp. The rest sets up a weak electric field in the brain. For 1 mA of tDCS or tACS over the human visual cortex, a computational model gives a cortical field of 0.417 V/m, assuming a gray matter conductivity of 0.24 S/m.\n\nThe waveform defines the variants. tDCS delivers a constant direct current, for example 1–2 mA, and its effect depends on the direction of current flow. At 1–2 mA it produces cortical fields up to about 0.4–0.8 V/m that polarize neuronal membranes below firing threshold. This modulates excitability, spontaneous firing and plasticity without directly evoking spikes. tACS delivers a sinusoidal, biphasic current through the same basic electrode montage. On average it does not shift the membrane potential, and its aim is to influence brain oscillations. tRNS applies a random electrical oscillation spectrum. Over the motor cortex, its 100–640 Hz components appear responsible for an increase in excitability. It is described as free of the current-direction sensitivity of tDCS.\n\nOn 8 December 2025 the US Food and Drug Administration approved a tDCS headset designed for home use, restricted to prescription, to treat moderate to severe major depressive disorder in adults. A treatment study in Alzheimer disease, registered as completed with 5 participants, planned 40 Hz tACS for 1 hour in 20 sessions."
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            "url": "https://www.scientificamerican.com/article/u-s-approves-first-device-to-treat-depression-with-brain-stimulation-at-home/"
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        "state": "known",
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          "note": "The 400 Hz transcranial pulsed-current protocol has a 2.5 ms pulse-onset-to-pulse-onset interval (1/400 Hz). Anodal or cathodal stimulation was delivered over M1 at 0.6 mA for 20 minutes. This is programmed pulse spacing, not neural response latency or the off-time between pulses.",
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        "value": {
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          "note": "Field-focality mesh volumes from SimNIBS v3.1.2 finite-element modeling of an MNI152 headreco head with 2×1 electrode montages around the targeted pre-supplementary motor area and right inferior frontal gyrus; currents are peak-to-peak amplitudes.",
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              "endpoint": "suprathreshold_volume"
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        "state": "unknown",
        "value": {
          "reason": "No. tES is a stimulation technique: it delivers a weak direct, alternating or random-noise current through scalp electrodes to modulate neuronal membrane potential, excitability or brain oscillations, and it does not measure or record any quantity."
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          "note": "tDCS drives a weak, subthreshold intracranial electric field (up to roughly 0.4-0.8 V/m at 1-2 mA) that polarizes neuronal membrane potential, modulating cortical excitability and firing rate without evoking action potentials directly. tACS delivers a sinusoidal, biphasic alternating current intended to influence endogenous brain oscillations, not to shift average membrane potential or to excite or inhibit cortex monotonically. tRNS applies a random electrical oscillation spectrum over the motor cortex and is proposed to increase its excitability, possibly through repeated opening of Na+ channels."
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          "note": "All three variants apply current from outside the head, so no tissue is penetrated, lesioned or removed. Conventional tDCS and low-intensity tACS deliver it through scalp electrodes without surgery or implants. tRNS, a non-invasive method, delivers it through conductive-rubber electrodes in saline-soaked sponges fixed by elastic bands, and is described as safe when used according to general tES safety guidelines. Typical effects of tDCS and tACS are mild and transient, and no serious adverse events were reported across over 18,000 low-intensity TES sessions."
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            "kind": "doi",
            "id": "10.1523/ENEURO.0248-21.2021",
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            "node": "01a0593a-6d74-7832-9f23-cc8c04f143ec",
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            "id": "10.1523/JNEUROSCI.4248-08.2008",
            "url": "https://doi.org/10.1523/JNEUROSCI.4248-08.2008"
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        ]
      },
      "cost": {
        "state": "known",
        "items": [
          {
            "value": {
              "kind": "instrument",
              "currency": "USD",
              "amount_min": 449.0,
              "year": 2026,
              "label": "ActivaDose tDCS Device Starter Kit, listed from"
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        ]
      },
      "theoretical": {
        "description": {
          "state": "known",
          "value": {
            "text": "Conventional 1–2 mA tDCS produces cortical fields up to about 0.4–0.8 V/m, below action-potential threshold and below typical animal-study fields; 0.8 V/m is a reported lower effectiveness limit. Reported neuronal-modulation thresholds for tACS range from 0.2 to about 1 V/m. A 1 mA extracranial tACS dose is estimated to give about 0.417 V/m, near or below threshold, and a 2 mA dose to be above it. Scalp shunting limits how much of the applied current reaches cortex. These are reported delivery-limiting factors, not a proven general physical bound. Tissue injury is reported at current densities of 6.3–13 A/m², more than 10 times conventional tDCS levels."
          },
          "node": "01a1578d-88bd-7440-92c5-5d9551f93cec",
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              "node": "01a054a0-f991-78c3-b28a-660fd542b2db",
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              "id": "10.1016/j.brs.2016.06.004",
              "url": "https://doi.org/10.1016/j.brs.2016.06.004"
            },
            {
              "node": "01a054a1-04a1-7011-826c-66db343c2da4",
              "kind": "doi",
              "id": "10.1016/j.clinph.2017.06.001",
              "url": "https://doi.org/10.1016/j.clinph.2017.06.001"
            },
            {
              "node": "01a054a1-1220-7333-8e91-c8f3e4a09e82",
              "kind": "doi",
              "id": "10.7554/elife.18834",
              "url": "https://doi.org/10.7554/elife.18834"
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            {
              "node": "01a054da-445e-73d0-9035-41aaf407077b",
              "kind": "doi",
              "id": "10.3389/fnhum.2013.00317",
              "url": "https://doi.org/10.3389/fnhum.2013.00317"
            },
            {
              "node": "01a054da-49f2-7b82-883b-2888f02f7483",
              "kind": "doi",
              "id": "10.3389/fnhum.2013.00279",
              "url": "https://doi.org/10.3389/fnhum.2013.00279"
            },
            {
              "node": "01a054da-884c-7cc0-bf18-4b3bb79f65b2",
              "kind": "doi",
              "id": "10.3389/fnsys.2022.827353",
              "url": "https://doi.org/10.3389/fnsys.2022.827353"
            }
          ]
        },
        "spatial_resolution_m": {
          "state": "known",
          "value": {
            "max": 0.01453,
            "unit": "m",
            "note": "Reported left-motor EACfree model results at 2 mA and EROI >0.25 V/m imply V≤1.605 cm³ and, under idealized spherical equivalence, d≤0.01453 m. This intentionally loose total-brain-volume substitution is a model-based geometric proxy, not measured two-target resolution. It conditionally applies to the same currents delivered as DC/tDCS within the study’s linear quasi-static model.",
            "endpoint": "suprathreshold_extent"
          },
          "node": "01a15102-a862-7e92-aa5c-f9282faf6a16",
          "sources": [
            {
              "node": "01a05934-fc37-7ea0-a9bd-bd56b2a56c5e",
              "kind": "doi",
              "id": "10.1016/j.neuroimage.2019.116124",
              "url": "https://doi.org/10.1016/j.neuroimage.2019.116124"
            }
          ]
        },
        "temporal_resolution_s": {
          "state": "incomplete"
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        "field_of_view_m3": {
          "state": "known",
          "value": {
            "min": 0.00111576,
            "max": 0.00123358,
            "unit": "m3",
            "note": "UK Biobank adult mean total brain volume used as the whole-brain value: 1.11576–1.23358 × 10⁻³ m³. These are anatomical reference volumes, not measured volumes of stimulated tissue in the modeling study’s participants.",
            "endpoint": "reachable_envelope",
            "operating_points": [
              {
                "label": "Female",
                "min": 0.00111576,
                "max": 0.00111576,
                "note": "UK Biobank adult mean total brain volume used as the whole-brain value.",
                "endpoint": "reachable_envelope"
              },
              {
                "label": "Male",
                "min": 0.00123358,
                "max": 0.00123358,
                "note": "UK Biobank adult mean total brain volume used as the whole-brain value.",
                "endpoint": "reachable_envelope"
              }
            ]
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          "node": "01a16d15-74db-7d63-b33c-2efac68aa2b8",
          "sources": [
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              "node": "01a054a1-1220-7333-8e91-c8f3e4a09e82",
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              "kind": "doi",
              "id": "10.1093/cercor/bhy109",
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          ]
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        "field_of_view_neurons": {
          "state": "incomplete"
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    {
      "slug": "tfus",
      "name": "Transcranial focused ultrasound",
      "group": {
        "id": "stim-noninvasive",
        "name": "Non-invasive write"
      },
      "mode": "write",
      "core": true,
      "summary": {
        "value": "Transcranial focused ultrasound (tFUS) is ultrasound aimed through the skull, without surgery, onto targets at the brain's surface or deep inside it. At low intensity, with little heating, the pulses appear to act mechanically on nerve-cell membranes, altering pressure-sensitive proteins and the opening and closing of ion channels; a thermal action is unlikely at these intensities. At higher intensities, the ultrasound can damage or destroy tissue.",
        "node": "01a15104-6d9b-70d1-ac93-15af3448223e",
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      "description": {
        "state": "known",
        "value": {
          "text": "Transcranial focused ultrasound (tFUS) focuses ultrasound noninvasively onto cortical or deep neural targets. A review describes focusing by constructive interference with wavelength-scale spatial resolution, about 3 mm at 0.5 MHz, and reports strong skull scattering above 1 MHz. A 256-element helmet-shaped array operates at 555 kHz. Its CT-informed full-wave treatment-planning model predicts an average in-situ focus of 2.2 × 2.2 × 3.1 mm at −6 dB at the lateral geniculate nucleus target, compared with 2.0 × 2.3 × 2.6 mm in water; these dimensions follow the helmet axes. A reviewed pulsed protocol uses 0.50 MHz ultrasound, 0.36 ms pulses at 1 kHz for 500 ms, and a spatial-peak pulse-average intensity of 16.95 W/cm². Low-intensity ultrasound appears to act mechanically on neuronal membranes, modifying mechanosensitive proteins and ion-channel gating. The mechanistic account considers thermal action unlikely for its cited low-heating pulses. Higher intensities can damage or ablate tissue."
        },
        "node": "01a15f3d-7f38-70e0-a0d8-fd7e5abb380c",
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      "spatial_resolution_m": {
        "state": "known",
        "value": {
          "min": 0.0022,
          "max": 0.0031,
          "unit": "m",
          "note": "For this treatment-planning protocol, the modeled −6 dB in-situ acoustic-pressure focus at the average LGN target measured [0.0022, 0.0022, 0.0031] m in [X,Y,Z] helmet coordinates; helmet axes are not necessarily aligned with the focal ellipsoid.",
          "endpoint": "focal_extent",
          "operating_points": [
            {
              "label": "Average LGN target, −6 dB in situ",
              "min": 0.0022,
              "max": 0.0031,
              "note": "Modeled acoustic-pressure focus: [X,Y,Z] = [0.0022, 0.0022, 0.0031] m in helmet coordinates.",
              "endpoint": "focal_extent"
            }
          ]
        },
        "node": "01a15111-9c16-7641-95ab-fc30d6f9c7ad",
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      "temporal_resolution_s": {
        "state": "known",
        "value": {
          "min": 0.001,
          "max": 0.001,
          "unit": "s",
          "note": "Interval between the starts of successive ultrasound pulses. The finest is in a pulsed protocol at 0.50 MHz with a 1 kHz pulse repetition frequency (0.36 ms pulses, 36% duty cycle, 500 pulses in a 500 ms stimulation): 1/1000 Hz = 1 ms. Coarser protocol timescales: a theta-burst protocol repeats 20 ms bursts every 200 ms (5 Hz) for 80 s, and an online protocol delivers 300 ms sonications every 3 s.",
          "endpoint": "inter_pulse_interval",
          "operating_points": [
            {
              "label": "Pulsed protocol, 1 kHz pulse repetition frequency",
              "min": 0.001,
              "max": 0.001,
              "note": "0.36 ms pulses within a 500 ms stimulation.",
              "endpoint": "inter_pulse_interval"
            },
            {
              "label": "Theta-burst protocol, successive 20 ms bursts",
              "min": 0.2,
              "max": 0.2,
              "note": "20 ms stimulation repeated every 200 ms (5 Hz).",
              "endpoint": "inter_pulse_interval"
            },
            {
              "label": "Online protocol, successive 300 ms sonications",
              "min": 3.0,
              "max": 3.0,
              "note": "300 ms pulses every 3 s.",
              "endpoint": "inter_pulse_interval"
            },
            {
              "label": "Pulse duration at 1 kHz PRF",
              "min": 0.00036,
              "max": 0.00036,
              "endpoint": "pulse_width"
            },
            {
              "label": "Theta-burst burst duration",
              "min": 0.02,
              "max": 0.02,
              "endpoint": "pulse_width"
            },
            {
              "label": "Online protocol sonication duration",
              "min": 0.3,
              "max": 0.3,
              "endpoint": "pulse_width"
            },
            {
              "label": "Theta-burst session",
              "min": 80.0,
              "max": 80.0,
              "endpoint": "session_duration"
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        "node": "01a15d8e-87c1-7182-ad7f-4cd924c366f9",
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      "field_of_view_m3": {
        "state": "known",
        "value": {
          "min": 3e-9,
          "max": 3e-9,
          "unit": "m3",
          "note": "The −3 dB focal volume at the geometric focus for the 555 kHz, 256-element array is 3 mm³, expressed here in cubic metres.",
          "endpoint": "suprathreshold_volume"
        },
        "node": "01a15112-61ef-7cb2-893f-816f7196a816",
        "sources": [
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            "id": "10.1038/s41467-025-63020-1",
            "url": "https://doi.org/10.1038/s41467-025-63020-1"
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        ]
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      "field_of_view_neurons": {
        "state": "incomplete"
      },
      "measurand": {
        "state": "unknown",
        "value": {
          "reason": "The tFUS apparatus only drives the transducer and characterizes its acoustic output by hydrophone; neural responses are separate EEG readouts from participants, not apparatus measurands."
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        "node": "01a14f35-e4d7-75c3-8129-baf43762b3f6",
        "sources": [
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            "node": "01a0e823-7269-7e33-b40d-9aa826f5a429",
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            "id": "10.1016/j.brs.2024.04.013",
            "url": "https://doi.org/10.1016/j.brs.2024.04.013"
          },
          {
            "node": "01a14f30-fd6c-73c2-841a-0a8398b6957e",
            "kind": "doi",
            "id": "10.1038/srep08743",
            "url": "https://doi.org/10.1038/srep08743"
          }
        ]
      },
      "stimulation": {
        "state": "known",
        "value": {
          "stimuli": [
            "low-intensity ultrasound"
          ],
          "note": "Low-intensity ultrasound appears to act mechanically on neuronal membranes, modifying mechanosensitive proteins and ion-channel gating."
        },
        "node": "01a0e1c6-9ef8-7991-bf25-154db21cf39c",
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      "destructiveness": {
        "state": "known",
        "value": {
          "kind": "non_destructive",
          "note": "Guideline-compliant neuromodulation had no reported tissue damage; human MRI/neurologic follow-up was negative through I_SPPA 11.6 W/cm². Two damage reports involved >0.65 MPa at 250–350 kHz."
        },
        "node": "01a0b22d-0eb9-7d30-b140-5a53f7e4ff28",
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      "preparation": {
        "state": "known",
        "value": {
          "steps": [
            {
              "kind": "other",
              "note": "Positioning/imaging preparation: align the participant to the transducer array using a custom stereotactic mask and, as needed, correct skull-induced distortion with multielement-array time/phase correction."
            }
          ],
          "note": "Ultrasound is applied through the intact skull without surgery or hair shaving."
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            "url": "https://doi.org/10.34133/research.0200"
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            "url": "https://doi.org/10.1038/s41467-025-63020-1"
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        ]
      },
      "cost": {
        "state": "known",
        "items": [
          {
            "value": {
              "kind": "instrument",
              "currency": "USD",
              "amount_min": 118900.0,
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              "label": "$118,900 — LOW INTENSITY FOCUSED ULTRASOUND DEVICE — BrainSonix Corporation — PIID 36C26119P1440; USD: a US federal (USAspending.gov) award record"
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      "theoretical": {
        "description": {
          "state": "known",
          "value": {
            "text": "Ideally, all-direction convergence gives a half-wavelength focus: ~1.5 mm at 0.5 MHz and ~0.75 mm at 1 MHz. Strong skull scattering above 1 MHz makes ~1 MHz the practical ceiling. The approximately 3 mm wavelength at 0.5 MHz gives a wavelength-scale estimate of practical focus size. A specific treatment-planning model instead gives a 2.2–3.1 mm −6 dB in-situ acoustic-pressure focus at the average LGN target: [2.2, 2.2, 3.1] mm in helmet coordinates, whose axes are not necessarily aligned with the focal ellipsoid. Skull heterogeneity distorts and shifts the focus and lowers thermal gain. Time/phase correction, especially simulation-based, can sharpen the focus and extend treatment below the transducer or centimeters from geometric focus, though standing waves and secondary hotspots remain possible."
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            "note": "In-principle ideal half-wavelength focal size for transcranial focused ultrasound. Arithmetic: wavelength ≈ 3 mm at 0.5 MHz, so λ/2 ≈ 1.5 mm = 0.0015 m. Assuming wavelength scales as 1/frequency (constant sound speed), λ ≈ 1.5 mm at 1 MHz, so λ/2 ≈ 0.75 mm = 0.00075 m. 1 MHz is the practical upper bound because the skull scatters strongly above 1 MHz. Caveats: this is an idealized bound that assumes waves converge from all directions; the 3 mm wavelength is approximate; practical resolution is only 'on the order of' the wavelength.",
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        "value": "Transcranial magnetic stimulation (TMS) is a noninvasive method in which a coil on the scalp sends pulsed magnetic fields that induce electric fields in the brain. It writes by altering neurons' membrane potentials and can trigger action potentials, mostly in superficial axons and cortical interneurons near the strongest field, and not in deep structures like the basal ganglia or thalamus. It reads indirectly: when aimed at motor cortex, muscle recordings measure motor-evoked potentials as an index of its effects. Repeated stimulation can cause longer-lasting changes and is used as therapy.",
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          "text": "TMS (transcranial magnetic stimulation) is noninvasive brain stimulation in which pulsed current in a coil held on the scalp creates a pulsed magnetic field. That field induces an electric field in the brain tissue, which alters neuronal membrane potentials and can evoke action potentials. Action potentials are evoked preferentially near the electric-field maxima, whose location is set by coil geometry and placement, in superficial axons and in cortical interneurons that feed pyramidal cells, and not in the deep basal ganglia or thalamus. Single and paired pulses are used to probe brain function. Repetitive TMS (rTMS) produces longer-lasting changes in activity and is used therapeutically, with a hand-held or helmet-like coil; a typical initial treatment course is 20–30 daily sessions, five days a week for 4–6 weeks, each lasting 3–45 minutes."
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          "note": "TMS is non-invasive. Estimated single-pulse heating is <0.1 °C. Sparse human studies detected no structural changes after rTMS, but this alone does not prove zero tissue damage. Active rTMS produced ~28% headache and 39% pain/discomfort (sham: 16%/15%); coil noise exceeded 140 dB SPL. Surveys reported 24 seizures in >300,000 sessions (7/100,000), including 19 in elevated-risk subjects (33/100,000)."
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          "value": {
            "text": "In a spherically symmetric, uniformly conducting head model, at TMS’s quasi-static frequencies the electric field is always stronger at the surface than inside and zero at the exact center, so direct near-center stimulation “appears impossible.” Maximum half-value depth is 3.5 cm—half the modeled brain radius—requiring the least-focal half-value spread, 308 cm²; no analyzed coil is both deep and focal."
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            "min": 0.02236,
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            "unit": "m",
            "note": "These are spherical-head simulation results, not measured human performance. Among 50 simulated TMS coils in a spherical head model, the smallest tangential spread S_(1/2) was 5 cm^2, reached by the three-layered double coil (#21), a figure-8 type coil with half-value depth d_(1/2) of 0.9 cm. The linear scale is stipulated as sqrt(S_(1/2)) = sqrt(5 cm^2) ≈ 2.236 cm. The 5 cm^2 value is reported to one significant figure, so the four-figure result reflects arithmetic, not measurement precision. No simulated coil significantly beat the figure-8 depth–focality tradeoff curve. In the simulation, coils with deeper field penetration could not be as focal as more superficial coils. The model's maximum half-value depth is 3.5 cm, which is half the brain radius. The flux-ball limit, S_(1/2) = 308 cm^2, is the least focal configuration possible, not the resolution. Coil #21 has a mean loop diameter of about 2 cm, which approaches the smallest practical diameter. Very small coils may be impractical for human TMS because the field attenuates rapidly with depth, so they need excessively high currents to reach threshold.",
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          "value": {
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            "unit": "s",
            "note": "Refractory intervals for DBS-evoked local responses and corticospinal D-wave axons in human patients, from the DBS absolute refractory period to complete D-wave recovery. The DBS local response most likely represents nonsynaptic, direct activation of local neuronal elements.",
            "endpoint": "inter_pulse_interval",
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                "note": "Mean 0.00056 s (SD 0.00008 s); 17 human patients; intraoperative DBS recording at subthalamic, pallidal and thalamic targets. Defined as the first interstimulus interval among three consecutive paired-pulse ratios <0.2.",
                "endpoint": "inter_pulse_interval"
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              {
                "label": "Neural relative refractory period: full recovery (measured in DBS-evoked responses)",
                "min": 0.00294,
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                "note": "Mean 0.00294 s (SD 0.00105 s); 17 human patients; intraoperative DBS recording at subthalamic, pallidal and thalamic targets. Defined as the first interstimulus interval among three consecutive paired-pulse ratios >0.98.",
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                "endpoint": "inter_pulse_interval"
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                "endpoint": "inter_pulse_interval"
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            {
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        "value": {
          "reason": "Not applicable for fixed histological tracing: the two-week interval precedes perfusion and sectioning and is a survival time, not an interval between repeated readouts."
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    {
      "slug": "tsms",
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          "reason": "Not applicable: continuous static magnetic-field exposure has no pulse-to-pulse interval; application and after-effect durations describe different quantities."
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      "slug": "ulm",
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        "name": "Optical & ultrasound (in vivo)"
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        "value": "Ultrasound localization microscopy is a super-resolution ultrasound method mapping the brain's blood vessels. Gas-filled microbubbles in the bloodstream are imaged at raw frame rates of hundreds per second; each bubble's position is estimated with a precision limited by how well its echo can be timed, and positions gathered over minutes build a vessel map with a reported tenfold resolution improvement over conventional ultrasound. Functional ULM in rat brain follows stimulus-evoked microbubble-flux changes at 1 s resolution using sliding-window maps over repeated stimulations. Bubble motion gives blood-flow speed, so flow is inferred from a tracer. In a patient study it imaged through the intact skull via the temporal bone, reaching 25 micrometres. In rat cortex through a thinned skull, two branching vessels 16 micrometres apart were clearly separated.",
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        "value": {
          "text": "Ultrasound localization microscopy (ULM) is a super-resolution ultrasound method that maps blood vessels by localizing individual contrast microbubbles. Gas-filled microbubbles injected into the bloodstream are imaged with ultrafast ultrasound; raw imaging above 500 frames/s tracks bubbles for tens of milliseconds. Functional ULM in rat brain resolves stimulus-evoked microbubble-flux changes at 1 s using sliding-window maps over repeated stimulations; raw frame rate is not functional resolution. The best attainable resolution is limited by the localization precision of each microbubble, whose lower bound is the Cramér-Rao bound on estimating the arrival time of its echo. In a craniotomized rat, 77 million microbubble detections over 7.5 minutes were tracked into 1.1 million trajectories and accumulated into 9.8 µm voxels, from 150 × 150 × 99 µm beamformed voxels. The accumulated positions form a vascular map with a reported tenfold resolution improvement over conventional ultrasound, and the bubble motion along each track gives blood-flow speed, so flow is inferred from a tracer. The map fills with time: in a rat brain slice under steady infusion, an image with 100 µm pixels would be reconstructed within 10 s, 20 µm pixels take 60 s, 5 µm pixels get close to 4 minutes, and fully populating vessels below 25 µm might take more than 10 minutes. In rat cortex through a thinned skull, two branching vessels 16 µm apart were clearly separated. In a patient study, transcranial ULM imaged through the intact skull via the temporal bone window, which rarely exceeds 20 mm in diameter, with a maximum achievable resolution of 25 µm under that study's conditions at depths up to 120 mm and an intravenous cannula for the contrast agent; the skull attenuates and aberrates the sound, and a correction of the aberration delay performed well in patients."
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        "value": {
          "min": 0.000016,
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          "unit": "m",
          "note": "Rat cortex through a thinned skull: two branching vessels 16 µm apart were still clearly separated. Finer figures come from a velocity criterion: adjacent bins count as distinct when their microbubble velocity distributions differ statistically.",
          "endpoint": "two_source_separation",
          "operating_points": [
            {
              "label": "Rat cortex, vessel profile width",
              "min": 9e-6,
              "max": 9e-6,
              "note": "9 µm FWHM vessel profile, a convolution of vessel size and method response, giving an upper limit to the resolution.",
              "endpoint": "point_spread"
            },
            {
              "label": "Rat functional ULM, deep regions, velocity criterion",
              "min": 6.5e-6,
              "max": 6.5e-6,
              "note": "Maps on a 6.25 × 6.875 µm grid; neighbouring-pixel velocity statistics confirmed this resolution, stated as 6.5 µm.",
              "endpoint": "sampling"
            },
            {
              "label": "Rat cortex, thinned skull, velocity criterion",
              "min": 8e-6,
              "max": 0.000012,
              "note": "Adjacent 8–12 µm resolution cells distinct by velocity distributions (P < 0.05).",
              "endpoint": "sampling"
            },
            {
              "label": "Human, transcranial, velocity criterion",
              "min": 0.000025,
              "max": 0.000025,
              "note": "25 µm bins near a vessel edge still showed significant speed differences, in diastole only; the study's maximum achievable resolution.",
              "endpoint": "sampling"
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        "state": "known",
        "value": {
          "min": 1.0,
          "max": 1.0,
          "unit": "s",
          "note": "Functional ULM in rat brain followed stimulus-evoked changes in microbubble flux at a stated 1 s temporal resolution, using sliding-window maps accumulated over repeated whisker stimulations; single trials suffice in 30 µm arterioles and about 10 repetitions are needed in 10 µm vessels. Structural vascular maps need minutes of accumulation.",
          "endpoint": "recoverable_timing",
          "operating_points": [
            {
              "label": "Rat fULM, 1 s window",
              "min": 1.0,
              "max": 1.0,
              "note": "Activation map with a 1 s window and 0.5 s step did not degrade under SVD analysis.",
              "endpoint": "recoverable_timing"
            },
            {
              "label": "3D transcranial mouse raw volume rate",
              "min": 0.004,
              "max": 0.004,
              "note": "250 Hz volume rate.",
              "endpoint": "sample_interval"
            },
            {
              "label": "Rat fULM, 5 s window with 20 stimulations",
              "min": 100.0,
              "max": 100.0,
              "note": "Each map built from 100 s of accumulated data.",
              "endpoint": "acquisition_duration"
            },
            {
              "label": "Image saturation in a separate study",
              "min": 300.0,
              "max": 300.0,
              "note": "5 million cumulative microbubbles; depends on microbubble concentration.",
              "endpoint": "acquisition_duration"
            },
            {
              "label": "Continuous 3D mouse acquisition per condition",
              "min": 300.0,
              "max": 300.0,
              "note": "Five continuous minutes awake or under isoflurane at 250 Hz.",
              "endpoint": "acquisition_duration"
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        "value": {
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          "note": "Stipulating an 80° sector with apex at the probe, 0.12 m maximum depth, and constant 0.006 m thickness: V=(80/360)×π×(0.12 m)^2×0.006 m=6.03×10^-5 m³ per acquisition. True ultrasound thickness varies with depth; imaging is best near the 60–70 mm elevation focus.",
          "endpoint": "acquired_volume"
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      "measurand": {
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        "value": {
          "measurands": [
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          "note": "It tracks intravenously injected ultrasound contrast microbubbles and uses their motion to quantify blood-flow speed, so flow is inferred from a tracer."
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          "note": "For brain tissue, transcranial insonation with intravenous microbubbles does not lesion or remove tissue by design, and no brain damage was found. Direct evidence of insonation safety is absent."
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              "kind": "other",
              "note": "Place an intravenous cannula in the medial cubital vein."
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              "note": "Inject an ultrasound contrast agent through the cannula."
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          "note": "The reported protocol requires intravenous access and an ultrasound contrast agent."
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        "description": {
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          "value": {
            "text": "The theoretical (Cramer-Rao-type) lower bound on microbubble-echo localization precision is about 2 µm axially at 7 MHz. Structural map accumulation time differs from functional temporal resolution. Functional ULM in rat brain follows evoked changes in 1 s sliding windows, with repeated stimulations needed for smaller vessels. In a rat brain coronal slice acquired under a steady 0.8 ml/kg infusion, a map at 100 µm pixels, or of 70–100 µm vessels, forms within 10 s. It takes 60 s for 20 µm pixels and gets close to 4 minutes for 5 µm pixels. 30–50 µm vessels need at least 40 s, and fully populating all vessels below 25 µm might take more than 10 minutes. Under those study conditions, complete capillary reconstruction was projected to take about ten minutes. The study projected roughly an order of magnitude longer at a clinical dose of 0.03 ml/kg. Acquisition times of over 10 minutes are estimated for microvascular targets at 5 cm depth and λ/20. Transcranial coverage through both temporal windows is a proposed whole-brain extension, represented by the stipulated large-brain anatomical reference of 1.23358 liters."
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            "id": "https://clinicaltrials.gov/api/v2/studies/NCT01325623",
            "url": "https://clinicaltrials.gov/api/v2/studies/NCT01325623"
          }
        ]
      },
      "stimulation": {
        "state": "known",
        "value": {
          "stimuli": [
            "electrical activation of vagal nerve fibers"
          ],
          "note": "Drives A- and B-fiber (and disputedly C-fiber) afferent and efferent axons of the cervical vagus nerve; brain effects arise indirectly through afferent projections to the nucleus tractus solitarius rather than through any direct action on brain tissue."
        },
        "node": "01a0d3b8-5b28-7151-b6d6-86fb67d3a20e",
        "sources": [
          {
            "node": "01a05915-2bef-75a1-8554-44b454302c3c",
            "kind": "doi",
            "id": "10.3389/fnins.2021.790943",
            "url": "https://doi.org/10.3389/fnins.2021.790943"
          },
          {
            "node": "01a05915-7c46-7933-862d-44ac0a33410c",
            "kind": "doi",
            "id": "10.1007/s40473-014-0010-5",
            "url": "https://doi.org/10.1007/s40473-014-0010-5"
          },
          {
            "node": "01a0599b-c09e-7a52-9a0f-1a4f99e9b747",
            "kind": "doi",
            "id": "10.3390/brainsci14070675",
            "url": "https://doi.org/10.3390/brainsci14070675"
          },
          {
            "node": "01a0599b-de94-7930-b500-0b5575c9f445",
            "kind": "doi",
            "id": "10.1016/j.neurot.2023.e00308",
            "url": "https://doi.org/10.1016/j.neurot.2023.e00308"
          }
        ]
      },
      "destructiveness": {
        "state": "known",
        "value": {
          "kind": "minimally_destructive",
          "note": "Implantation causes local surgical-access damage through neck and chest incisions, opening the carotid sheath, forming a subcutaneous generator pocket, and tunneling the lead; no destruction of the vagus nerve or brain tissue is described as the technique’s purpose."
        },
        "node": "01a0b7cd-66bd-7272-9288-2164b71e61a2",
        "sources": [
          {
            "node": "01a0599b-c09e-7a52-9a0f-1a4f99e9b747",
            "kind": "doi",
            "id": "10.3390/brainsci14070675",
            "url": "https://doi.org/10.3390/brainsci14070675"
          },
          {
            "node": "01a0599b-de94-7930-b500-0b5575c9f445",
            "kind": "doi",
            "id": "10.1016/j.neurot.2023.e00308",
            "url": "https://doi.org/10.1016/j.neurot.2023.e00308"
          }
        ]
      },
      "preparation": {
        "state": "known",
        "value": {
          "steps": [
            {
              "kind": "surgery",
              "note": "Typically outpatient implantation of a programmable pulse generator: neck incision and carotid-sheath dissection expose the vagus nerve; a subclavicular subcutaneous generator pocket is created and the lead tunneled to it."
            },
            {
              "kind": "anesthesia",
              "note": "General anesthesia."
            }
          ],
          "note": "No genetic-engineering or germline preparation is described."
        },
        "node": "01a0b7d4-8c9a-73b0-b506-062cb5bd6227",
        "sources": [
          {
            "node": "01a05915-7c46-7933-862d-44ac0a33410c",
            "kind": "doi",
            "id": "10.1007/s40473-014-0010-5",
            "url": "https://doi.org/10.1007/s40473-014-0010-5"
          },
          {
            "node": "01a0599b-c09e-7a52-9a0f-1a4f99e9b747",
            "kind": "doi",
            "id": "10.3390/brainsci14070675",
            "url": "https://doi.org/10.3390/brainsci14070675"
          }
        ]
      },
      "cost": {
        "state": "known",
        "items": [
          {
            "value": {
              "kind": "procedure",
              "currency": "USD",
              "amount_min": 45000.5,
              "year": 2026,
              "label": "Medicare OPPS 64568 cranial-nerve neurostimulator implantation"
            },
            "node": "01a06f3b-0ea5-76a0-a4da-99bbe24a0a9b",
            "sources": [
              {
                "node": "01a05972-2dc8-7091-9c27-760e9af9e164",
                "kind": "url",
                "id": "https://www.cms.gov/files/zip/july-2026-opps-addendum-b.zip",
                "url": "https://www.cms.gov/files/zip/july-2026-opps-addendum-b.zip"
              }
            ]
          },
          {
            "value": {
              "kind": "procedure",
              "currency": "USD",
              "amount_min": 3490.14,
              "year": 2026,
              "label": "Medicare OPPS 64570 neurostimulator removal"
            },
            "node": "01a06f3b-1621-7100-9bcd-792c2a9ca252",
            "sources": [
              {
                "node": "01a05972-2dc8-7091-9c27-760e9af9e164",
                "kind": "url",
                "id": "https://www.cms.gov/files/zip/july-2026-opps-addendum-b.zip",
                "url": "https://www.cms.gov/files/zip/july-2026-opps-addendum-b.zip"
              }
            ]
          },
          {
            "value": {
              "kind": "session",
              "currency": "USD",
              "amount_min": 38.13,
              "amount_max": 97.13,
              "year": 2026,
              "label": "Medicare OPPS 95976/95977 simple vs complex programming"
            },
            "node": "01a06f3b-1d47-7db3-9fd1-e17bd7e08836",
            "sources": [
              {
                "node": "01a05972-2dc8-7091-9c27-760e9af9e164",
                "kind": "url",
                "id": "https://www.cms.gov/files/zip/july-2026-opps-addendum-b.zip",
                "url": "https://www.cms.gov/files/zip/july-2026-opps-addendum-b.zip"
              }
            ]
          },
          {
            "value": {
              "kind": "procedure",
              "currency": "AUD",
              "amount_min": 50000.0,
              "amount_max": 50000.0,
              "label": "Non-subsidized VNS device plus implantation procedure, approximate figure (~AU$50,000)"
            },
            "node": "01a090ca-c88f-7a43-85d6-6586a5e4ec08",
            "sources": [
              {
                "node": "01a05915-55c8-7f90-8438-8d19daf3a7c4",
                "kind": "doi",
                "id": "10.1186/s42494-025-00219-1",
                "url": "https://doi.org/10.1186/s42494-025-00219-1"
              },
              {
                "node": "01a05915-d4bc-74b1-ba58-e301c62d7324",
                "kind": "doi",
                "id": "10.3389/fnins.2020.00284",
                "url": "https://doi.org/10.3389/fnins.2020.00284"
              }
            ]
          }
        ]
      },
      "theoretical": {
        "description": {
          "state": "known",
          "value": {
            "text": "Spatial: allocating the pooled mean cross-sectional area of the human cervical vagus nerve (5.49 mm²) equally among its mean 6.25 fascicles, each as a circle, gives a diameter of about 1.06 mm per fascicle. This is a geometric proxy for the finest unit a nerve electrode could address, not an observed fascicle diameter or a measured selective-stimulation resolution. Time: in human peripheral nerve, the reported absolute refractory period is 0.6–0.7 ms in the median nerve and 0.75 ms in median sensory fibres; in 20 ulnar motor nerves a second response first exceeds 5% at a mean 1.16 ± 0.18 ms and exceeds 95% at 2.11 ± 0.50 ms."
          },
          "node": "01a15d87-7652-7073-b0ab-86eb9c3f7728",
          "sources": [
            {
              "node": "01a0e313-99c7-7b03-86f0-69917ec96edc",
              "kind": "doi",
              "id": "10.1136/jnnp.41.9.784",
              "url": "https://doi.org/10.1136/jnnp.41.9.784"
            },
            {
              "node": "01a0e570-0b90-70b2-aa2f-fd9de33a7fbc",
              "kind": "doi",
              "id": "10.3389/fnins.2026.1731234",
              "url": "https://doi.org/10.3389/fnins.2026.1731234"
            }
          ]
        },
        "spatial_resolution_m": {
          "state": "known",
          "value": {
            "min": 0.00105755,
            "max": 0.00105755,
            "unit": "m",
            "note": "Reported pooled means of 5.49 mm² nerve area and 6.25 fascicles give d≈0.00106 m under equal-area circular allocation of the entire cross-section. This geometric proxy is neither observed fascicle diameter nor measured selective-stimulation resolution."
          },
          "node": "01a14f9c-1807-7bf0-a3ad-1ce7ff96a863",
          "sources": [
            {
              "node": "01a0e570-0b90-70b2-aa2f-fd9de33a7fbc",
              "kind": "doi",
              "id": "10.3389/fnins.2026.1731234",
              "url": "https://doi.org/10.3389/fnins.2026.1731234"
            }
          ]
        },
        "temporal_resolution_s": {
          "state": "known",
          "value": {
            "min": 0.0006,
            "max": 0.0007,
            "unit": "s",
            "note": "Reported human ulnar response-recovery intervals and reported median-nerve refractory values.",
            "endpoint": "inter_pulse_interval",
            "operating_points": [
              {
                "label": "Ulnar motor nerve, test response >5%",
                "min": 0.00098,
                "max": 0.00134,
                "note": "Reported mean 0.00116 s ± 0.00018 s SD in 20 ulnar nerves.",
                "endpoint": "inter_pulse_interval"
              },
              {
                "label": "Ulnar motor nerve, test response >95%",
                "min": 0.00161,
                "max": 0.00261,
                "note": "Reported mean 0.00211 s ± 0.00050 s SD.",
                "endpoint": "inter_pulse_interval"
              },
              {
                "label": "Median nerve, absolute refractory period",
                "min": 0.0006,
                "max": 0.0007,
                "note": "Reported median-nerve absolute refractory values.",
                "endpoint": "inter_pulse_interval"
              },
              {
                "label": "Median sensory fibres, absolute refractory period",
                "min": 0.00075,
                "max": 0.00075,
                "note": "Reported median sensory-fibre value.",
                "endpoint": "inter_pulse_interval"
              }
            ]
          },
          "node": "01a165e4-00ec-7460-abad-5bc5088c3441",
          "sources": [
            {
              "node": "01a0e313-99c7-7b03-86f0-69917ec96edc",
              "kind": "doi",
              "id": "10.1136/jnnp.41.9.784",
              "url": "https://doi.org/10.1136/jnnp.41.9.784"
            }
          ]
        },
        "field_of_view_m3": {
          "state": "incomplete"
        },
        "field_of_view_neurons": {
          "state": "incomplete"
        }
      }
    },
    {
      "slug": "voltage-imaging-gevi",
      "name": "Voltage imaging (GEVI)",
      "group": {
        "id": "optical",
        "name": "Optical & ultrasound (in vivo)"
      },
      "mode": "read",
      "core": true,
      "summary": {
        "value": "Voltage imaging with genetically encoded indicators is fluorescence microscopy of neurons that carry a protein sensor whose brightness changes with membrane voltage; two-photon excitation reaches the sensor in deep tissue. What it reads is voltage-dependent fluorescence, an indirect measure from which spikes and slower subthreshold changes are inferred. In mice, viral delivery confined the indicator to excitatory neurons of visual cortex layer 2/3, enriched at their cell bodies and nearest dendrites, and traces from awake animals yielded inferred spikes and slow voltage changes; in larval zebrafish, spike-like transients were detected.",
        "node": "01a151cc-2907-7052-a264-06f8a5aafd99",
        "sources": [
          {
            "node": "01a15161-4d18-7ab2-9793-b2e6e13c2bc6",
            "kind": "doi",
            "id": "10.1016/j.cell.2022.07.013",
            "url": "https://doi.org/10.1016/j.cell.2022.07.013"
          },
          {
            "node": "01a15169-ae53-7ac1-a790-c00b0231afe7",
            "kind": "doi",
            "id": "10.1038/s41598-026-58107-8",
            "url": "https://doi.org/10.1038/s41598-026-58107-8"
          }
        ]
      },
      "row_node": "01a15d53-0f37-7643-86ee-37f204633642",
      "description": {
        "state": "known",
        "value": {
          "text": "Genetically encoded voltage indicators are protein biosensors whose fluorescence brightness changes with membrane voltage. Indicators built by coupling a fluorescent protein to a voltage-sensitive phosphatase domain combine voltage sensing and fluorescence modulation in one genetically encoded molecule. Their fluorescence-versus-voltage relation can be sigmoidal, consistent with voltage-sensitive-domain behavior. Two-photon optical excitation permits visualization in deep tissue, while fluorescence detection measures voltage-dependent brightness changes that report neuronal voltage dynamics.\n\nIn a mouse protocol, Cre-dependent AAVs delivered indicator genes to visual-cortex layer 2/3 in transgenic mice expressing Cre in excitatory cells. A short Kv2.1-derived peptide restricted the indicator to somata and proximal dendrites to minimize neuropil background. Ring-like fluorescence was consistent with plasma-membrane localization and somatic enrichment. This genetic targeting confines expression to the Cre-defined cell population, and two-photon visualization provides optical access to fluorescence from labeled neurons in tissue. Within this scope, detected fluorescence brightness tracks neuronal membrane voltage, while the expression strategy determines cell-type targeting and subcellular localization."
        },
        "node": "01a15191-aa44-7cb1-9110-4a7772722672",
        "sources": [
          {
            "node": "01a15161-4d18-7ab2-9793-b2e6e13c2bc6",
            "kind": "doi",
            "id": "10.1016/j.cell.2022.07.013",
            "url": "https://doi.org/10.1016/j.cell.2022.07.013"
          }
        ]
      },
      "spatial_resolution_m": {
        "state": "known",
        "value": {
          "min": 0.00004,
          "max": 0.00006,
          "unit": "m",
          "note": "In-vivo mouse cortical voltage imaging tracked sparsely labelled V1-to-LM neuronal somata separated by approximately 40–60 µm, about 150 µm below the brain surface, with wide-field epifluorescence at 1 kHz. This is a demonstrated soma-separation range, not a measured minimum optical resolution. The bead calibration characterizes the FlatMux two-photon platform, a different system from the wide-field neuronal experiment.",
          "endpoint": "two_source_separation",
          "operating_points": [
            {
              "label": "Separate FlatMux two-photon platform: dual-plane bead calibration, 150 µm axial offset",
              "min": 6.1e-7,
              "max": 1.35e-6,
              "note": "Lateral Gaussian FWHM on 0.5 µm fluorescent beads in a different imaging system from the wide-field neuronal experiment; finest value 0.61 µm.",
              "endpoint": "point_spread"
            }
          ]
        },
        "node": "01a15ce4-f5ba-7ce1-9aa2-d4b0987f3e48",
        "sources": [
          {
            "node": "01a15169-ba13-7990-9765-fdc16b7deb10",
            "kind": "doi",
            "id": "10.1038/s41592-026-03158-y",
            "url": "https://doi.org/10.1038/s41592-026-03158-y"
          },
          {
            "node": "01a15cc4-e4db-7d70-9e2e-6355197c9e3b",
            "kind": "doi",
            "id": "10.1126/science.aab0810",
            "url": "https://doi.org/10.1126/science.aab0810"
          }
        ]
      },
      "temporal_resolution_s": {
        "state": "known",
        "value": {
          "min": 0.008,
          "max": 0.008,
          "unit": "s",
          "note": "Scanless two-photon voltage imaging of JEDI-2P-Kv in mouse dentate-gyrus organotypic slices resolved single action potentials in spike trains up to 125 Hz, an 8 ms interval, with 1 kHz acquisition at power densities of at least 0.66 mW µm^-2.",
          "endpoint": "recoverable_timing",
          "operating_points": [
            {
              "label": "Scanless 2P, organotypic slices, 500 Hz imaging",
              "min": 0.01,
              "max": 0.01,
              "note": "Individual action potentials tracked in trains up to 100 Hz; 500 Hz was insufficient for robust tracking in 125 Hz trains.",
              "endpoint": "recoverable_timing"
            },
            {
              "label": "Single-cell scanless two-photon imaging, mouse dentate-gyrus organotypic slices, 500 Hz",
              "min": 0.002,
              "max": 0.002,
              "note": "Tracked individual action potentials in trains up to 100 Hz. This cadence was insufficient for robust tracking in 125 Hz trains.",
              "endpoint": "sample_interval"
            },
            {
              "label": "Single-cell scanless two-photon imaging, mouse dentate-gyrus organotypic slices, 1 kHz",
              "min": 0.001,
              "max": 0.001,
              "note": "At power densities of at least 0.66 mW µm⁻², 125 Hz train recordings had better detection probability and fluorescence response than recordings at 500 Hz.",
              "endpoint": "sample_interval"
            },
            {
              "label": "Single-soma ULoVE recording, head-fixed running mouse",
              "min": 0.0002,
              "max": 0.0004,
              "note": "Single somas were recorded at 2.5–5 kHz using two sequential excitation patterns and 15 mW power.",
              "endpoint": "sample_interval"
            },
            {
              "label": "Paired-cell ULoVE recording, mouse visual-cortex layer 2/3",
              "min": 0.0004,
              "max": 0.0004,
              "note": "Pairs were recorded at 2.5 kHz without decreasing dwell time per cell; action potentials were easily detectable.",
              "endpoint": "sample_interval"
            },
            {
              "label": "Dual-plane neuronal population voltage imaging, mouse cortical layers 2/3 and 4",
              "min": 0.00133,
              "max": 0.00133,
              "note": "Approximate interval at the stated 752 Hz frame rate; 180 neurons were identified across the two planes.",
              "endpoint": "sample_interval"
            },
            {
              "label": "High-SNR in vivo population voltage imaging, awake mouse",
              "min": 0.00133,
              "max": 0.00133,
              "note": "Approximate interval at the stated 752 Hz frame rate; the two protocols identified 18 and 22 neurons.",
              "endpoint": "sample_interval"
            },
            {
              "label": "Volumetric voltage imaging, live 4–6 dpf larval zebrafish",
              "min": 0.005,
              "max": 0.005,
              "note": "Volumes were acquired at up to 200 volumes per second using 28 sequential images per scan, including 25 x-slices and 3 discarded settling images; recordings lasted up to 31 s.",
              "endpoint": "sample_interval"
            }
          ]
        },
        "node": "01a15cf7-2cb6-7bf0-99ac-5ec3a666de97",
        "sources": [
          {
            "node": "01a15161-4d18-7ab2-9793-b2e6e13c2bc6",
            "kind": "doi",
            "id": "10.1016/j.cell.2022.07.013",
            "url": "https://doi.org/10.1016/j.cell.2022.07.013"
          },
          {
            "node": "01a15163-6722-7b32-aa30-28852da170a6",
            "kind": "doi",
            "id": "10.1038/s41467-024-49192-2",
            "url": "https://doi.org/10.1038/s41467-024-49192-2"
          },
          {
            "node": "01a15169-ae53-7ac1-a790-c00b0231afe7",
            "kind": "doi",
            "id": "10.1038/s41598-026-58107-8",
            "url": "https://doi.org/10.1038/s41598-026-58107-8"
          },
          {
            "node": "01a15169-ba13-7990-9765-fdc16b7deb10",
            "kind": "doi",
            "id": "10.1038/s41592-026-03158-y",
            "url": "https://doi.org/10.1038/s41592-026-03158-y"
          },
          {
            "node": "01a15169-c291-7613-b8ca-a7ce279a69d3",
            "kind": "doi",
            "id": "10.1038/s41592-026-03158-y",
            "url": "https://doi.org/10.1038/s41592-026-03158-y"
          }
        ]
      },
      "field_of_view_m3": {
        "state": "known",
        "value": {
          "min": 1.8685e-11,
          "max": 1.8685e-11,
          "unit": "m3",
          "note": "Volumetric field of view of the oblique plane microscope protocol, reconstructed by affine transformation: 127 μm (x) × 678 μm (y) × 217 μm (z) = 18,685,002 μm3 ≈ 1.87e-11 m3. Scope: transgenic larval zebrafish at 4 to 6 dpf expressing Ace-mNeon2-Kv2.1 under the QFDBD-QUAS system, paralyzed with 0.25 mg/ml pancuronium bromide and exposed to and immersed in 20 mM PTZ. Cadence is up to 200 volumes per second (5 ms per volume, 5,600 Hz camera, 28 images per galvo cycle with 3 discarded, 25 x-slices, step size up to 3.2 to 5.3 μm), with recordings up to 31 s. Higher volume rates reduce the x field of view or axial sampling.",
          "endpoint": "acquired_volume"
        },
        "node": "01a15746-b10b-7a41-8914-16e9bf72d976",
        "sources": [
          {
            "node": "01a15169-ae53-7ac1-a790-c00b0231afe7",
            "kind": "doi",
            "id": "10.1038/s41598-026-58107-8",
            "url": "https://doi.org/10.1038/s41598-026-58107-8"
          }
        ]
      },
      "field_of_view_neurons": {
        "state": "known",
        "value": {
          "min": 180.0,
          "max": 180.0,
          "unit": "neuron",
          "note": "Two-photon FlatMux voltage imaging of mouse cortex in dual-plane mode: 180 identified neurons (85 + 95) recorded simultaneously across two acquired planes, each 200 × 590 μm, at 165 μm (L2/3) and 315 μm (L4) depth in PPC with whisker stimulation; ASAP5, 752 Hz frame rate, 175 mW average power, spike SNR 3.2 ± 0.1. The count covers two discrete planes only, without the volume between them.",
          "endpoint": "sensing_envelope",
          "operating_points": [
            {
              "label": "Large-FOV, JEDI3sub",
              "min": 106.0,
              "max": 106.0,
              "note": "Single plane, 400 × 590 μm FOV at 200 μm depth; 752 Hz; 170 mW; cortical two-photon voltage imaging.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "Large-FOV, FORCE1s",
              "min": 87.0,
              "max": 87.0,
              "note": "Single plane, 400 × 590 μm FOV at 200 μm depth; 752 Hz; 175 mW.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "High-speed, FORCE1f (Fig. 3j–o)",
              "min": 43.0,
              "max": 43.0,
              "note": "Single plane, 200 × 375 μm FOV at 200 μm depth; 2,003 Hz; 150 mW.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "High-speed, FORCE1f (Fig. 3c–i)",
              "min": 24.0,
              "max": 24.0,
              "note": "Single plane, 200 × 375 μm FOV at 200 μm depth; 2,003 Hz; 160 mW.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "Deep, FORCE1s",
              "min": 55.0,
              "max": 55.0,
              "note": "Single plane, 200 × 590 μm FOV at 500 μm depth; 752 Hz; 150 mW.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "High-SNR, awake mouse, FORCE1s",
              "min": 22.0,
              "max": 22.0,
              "note": "140 × 140 μm FOV at 180 μm depth; 752 Hz; 82 mW. Other high-SNR configurations: 18 neurons (JEDI3sub, 112 × 140 μm, 140 μm depth, 70 mW) and 14 neurons (ASAP5, 112 × 140 μm, 200 μm depth, 90 mW), both at 752 Hz.",
              "endpoint": "sensing_envelope"
            },
            {
              "label": "Paired-cell ULoVE, JEDI-2P, head-fixed mouse",
              "min": 2.0,
              "max": 2.0,
              "note": "Two layer 2/3 visual cortex somas per recording at 2.5 kHz (reduced from 5 kHz to keep per-cell dwell time); single somas illuminated with 15 mW; cell separation 18–169 μm, depth 111–248 μm; 17 separate pairs, not pooled.",
              "endpoint": "sensing_envelope"
            }
          ]
        },
        "node": "01a1519e-ce6d-7500-b8b5-bf7cf0da3b8a",
        "sources": [
          {
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            "id": "10.1016/j.cell.2022.07.013",
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      "measurand": {
        "state": "known",
        "value": {
          "measurands": [
            "voltage-dependent fluorescence",
            "inferred action potentials",
            "inferred subthreshold membrane-voltage fluctuations"
          ],
          "note": "Fluorescence is the observed indirect voltage signal. JEDI-2P followed a sigmoidal voltage-step curve; awake mouse L2/3 two-photon traces yielded MLspike-inferred spikes and slow voltage changes. Larval zebrafish denoised Ace-mNeon2 ΔF/F₀ decreases yielded detected spike-like transients."
        },
        "node": "01a15192-c379-75b2-bd6f-16b348f5c1d4",
        "sources": [
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            "id": "10.1038/s41598-026-58107-8",
            "url": "https://doi.org/10.1038/s41598-026-58107-8"
          }
        ]
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      "stimulation": {
        "state": "unknown",
        "value": {
          "reason": "During neuronal reporter readout, QuasAr1 and QuasAr2 generate no detectable photocurrent under red light tested up to 900 W/cm² or tested blue light, and JEDI-2P fluorescence varies with voltage. Deliberate neural-writing output is inapplicable to these readouts; stimulation by a separate actuator is distinct."
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        "node": "01a15769-4cc3-7582-bc6d-be1274a8968a",
        "sources": [
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            "node": "01a15161-4d18-7ab2-9793-b2e6e13c2bc6",
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          }
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        "state": "known",
        "value": {
          "kind": "minimally_destructive",
          "note": "In mice, somatic AAV injection into layer 2/3 visual cortex is minimally destructive because it penetrates cortical tissue. The inherited-transgenic larval zebrafish protocol separately uses bath paralysis, PTZ exposure and agarose mounting."
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        "node": "01a151a1-2919-7b92-81fe-07e1c4d3a5b1",
        "sources": [
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            "node": "01a15161-4d18-7ab2-9793-b2e6e13c2bc6",
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          }
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        "state": "known",
        "value": {
          "steps": [
            {
              "kind": "germline_genetic_engineering",
              "note": "Mouse inherited-Cre protocol: use Slc17a7-Cre mice."
            },
            {
              "kind": "genetic_engineering",
              "note": "Mouse inherited-Cre protocol: inject Cre-dependent JEDI-2P AAV into visual cortex."
            },
            {
              "kind": "anesthesia",
              "note": "Mouse inherited-Cre protocol: use isoflurane surgical anesthesia with analgesia and local bupivacaine."
            },
            {
              "kind": "surgery",
              "note": "Mouse inherited-Cre protocol: open a craniotomy over the injection site, seal it with a coverslip, and cement a washer headbar to the skull."
            },
            {
              "kind": "other",
              "note": "Mouse inherited-Cre protocol: immobilize the head through the attached headbar."
            },
            {
              "kind": "genetic_engineering",
              "note": "Mouse viral-Cre protocol: co-inject Cre AAV and Cre-dependent JEDI-2P AAV into visual cortex of wild-type C57BL/6J mice."
            },
            {
              "kind": "anesthesia",
              "note": "Mouse viral-Cre protocol: use Zolethil-Xylazine surgical anesthesia with preoperative buprenorphine."
            },
            {
              "kind": "surgery",
              "note": "Mouse viral-Cre protocol: place and cement a coverslip over the targeted cortex and cement an aluminum head plate to the skull."
            },
            {
              "kind": "other",
              "note": "Mouse viral-Cre protocol: habituate mice progressively to head fixation before recording."
            },
            {
              "kind": "germline_genetic_engineering",
              "note": "Larval zebrafish protocol: use fluorescence-positive F2 transgenic reporter larvae on a casper or nacre background at 4–6 days post-fertilization."
            },
            {
              "kind": "other",
              "note": "Larval zebrafish protocol: paralyze larvae with pancuronium bromide and confirm paralysis by absent movement after tactile stimulation."
            },
            {
              "kind": "other",
              "note": "Larval zebrafish protocol: expose paralyzed larvae to PTZ, embed them in low-melting-point agarose, and maintain PTZ as the immersion medium during imaging."
            }
          ],
          "note": "The mouse Cre routes are alternative protocols; the larval zebrafish protocol is separate."
        },
        "node": "01a151b9-1308-71d0-8373-3edf24625ec7",
        "sources": [
          {
            "node": "01a15161-4d18-7ab2-9793-b2e6e13c2bc6",
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            "url": "https://doi.org/10.1016/j.cell.2022.07.013"
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            "node": "01a15169-ae53-7ac1-a790-c00b0231afe7",
            "kind": "doi",
            "id": "10.1038/s41598-026-58107-8",
            "url": "https://doi.org/10.1038/s41598-026-58107-8"
          }
        ]
      },
      "cost": {
        "state": "known",
        "items": [
          {
            "value": {
              "kind": "consumable",
              "currency": "USD",
              "amount_min": 94.0,
              "year": 2026,
              "label": "Addgene pAAV-hSyn-ASAP3-WPRE plasmid #132331, agar stab"
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            "node": "01a06f3b-4036-7123-adaf-02bf3c3a361a",
            "sources": [
              {
                "node": "01a05964-1ab1-7ab0-b300-a07987d631e1",
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                "url": "https://www.addgene.org/132331/"
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          },
          {
            "value": {
              "kind": "consumable",
              "currency": "USD",
              "amount_min": 459.0,
              "amount_max": 459.0,
              "label": "Voltron2-ST AAV1 #172907-AAV1, 100 µL at ≥7×10¹² vg/mL, including required plasmid DNA ($425 + $34)"
            },
            "node": "01a15cca-e0e9-7523-bfcf-bb23b635ed4e",
            "sources": [
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                "url": "https://www.addgene.org/172907/?tab=overview"
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            ]
          },
          {
            "value": {
              "kind": "instrument",
              "currency": "USD",
              "amount_min": 43800.0,
              "amount_max": 43800.0,
              "year": 2024,
              "label": "ORCA Quest qCMOS camera kit, US federal award 36C24E25P0004; detector component, excluding microscope and excitation optics"
            },
            "node": "01a15cce-7e72-72c0-8473-9a83be85d772",
            "sources": [
              {
                "node": "01a15cb9-c26e-73c2-9723-bcca189ceff2",
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                "id": "https://www.hamamatsu.com/us/en/applications/life-sciences/fluorescence-imaging/super-resolution-microscopy.html",
                "url": "https://www.hamamatsu.com/us/en/applications/life-sciences/fluorescence-imaging/super-resolution-microscopy.html"
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            ]
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        ]
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        "description": {
          "state": "incomplete"
        },
        "spatial_resolution_m": {
          "state": "known",
          "value": {
            "min": 3.7e-7,
            "max": 3.7e-7,
            "unit": "m",
            "note": "Theoretical lateral FWHM limit of 0.37 µm for the larval zebrafish whole-brain voltage-imaging remote-refocusing light-sheet system (×6.16 magnification). Optical-system conditional prediction, not an in-vivo neural functional resolution. Empirical calibration uses 200-nm beads (605-nm emission) in agarose under continuous scanning across a 206-µm axial range at 200.8 Hz. Measured FWHMs exceed theory because of motion blur (~3 µm axial travel per frame) and undersampling by the 0.73-µm effective pixel. Volume resolution is limited by pixel size and the 5–6 µm z-step; the Nyquist effective lateral resolution of 1.46 µm is a sampling figure, not a PSF.",
            "endpoint": "point_spread",
            "operating_points": [
              {
                "label": "Theoretical axial FWHM",
                "min": 1.21e-6,
                "max": 1.21e-6,
                "note": "Theoretical axial limit for the same optical system.",
                "endpoint": "point_spread"
              },
              {
                "label": "Measured lateral FWHM, 605-nm beads, continuous scan",
                "min": 1e-6,
                "max": 1e-6,
                "note": "~1 µm across the full Φ900 × 200 µm^3 FOV. Obtained from a 2D Gaussian fit to the downsampled PSF and inflated by pixel undersampling and motion blur.",
                "endpoint": "point_spread"
              },
              {
                "label": "Measured axial FWHM, 605-nm beads, continuous scan",
                "min": 3.5e-6,
                "max": 3.5e-6,
                "note": "~3.5 µm across the full FOV. Obtained from a dual-Gaussian fit to the z-profile and inflated by ~3 µm axial travel per frame.",
                "endpoint": "point_spread"
              },
              {
                "label": "Nyquist effective lateral resolution from 0.73-µm pixel",
                "min": 1.46e-6,
                "max": 1.46e-6,
                "note": "Sampling-limited figure, not a PSF width.",
                "endpoint": "sampling"
              }
            ]
          },
          "node": "01a1575c-d7e4-7181-b1e2-92e952a299a3",
          "sources": [
            {
              "node": "01a15758-34fe-76f2-a295-1640e5db47d1",
              "kind": "doi",
              "id": "10.1038/s41592-026-03179-7",
              "url": "https://doi.org/10.1038/s41592-026-03179-7"
            }
          ]
        },
        "temporal_resolution_s": {
          "state": "incomplete"
        },
        "field_of_view_m3": {
          "state": "known",
          "value": {
            "min": 1.272e-10,
            "max": 1.272e-10,
            "unit": "m3",
            "note": "Modeled cylindrical 3D-FOV for larval zebrafish whole-brain voltage imaging, diameter 900 um by depth 200 um: pi x (450e-6 m)^2 x (200e-6 m) = pi x 2.025e-7 m2 x 2e-4 m = pi x 4.05e-11 m3 = about 1.272e-10 m3 (about 0.127 mm3). A Zemax model of the detection path (three custom tube lenses, a PBS and a relay lens pair, excluding the detection and remote objectives) gives diffraction-limited performance over this volume at NA 1.0, with 0.15 lambda RMS wavefront error at 550 nm at the FOV edge. Relay magnification is about x6.16. This figure is a model-constrained optical envelope and does not guarantee a recording volume for functional neurons.",
            "endpoint": "reachable_envelope"
          },
          "node": "01a1575d-6b50-77f1-8699-a25ccc28ebf4",
          "sources": [
            {
              "node": "01a15758-34fe-76f2-a295-1640e5db47d1",
              "kind": "doi",
              "id": "10.1038/s41592-026-03179-7",
              "url": "https://doi.org/10.1038/s41592-026-03179-7"
            }
          ]
        },
        "field_of_view_neurons": {
          "state": "incomplete"
        }
      }
    },
    {
      "slug": "volume-em",
      "name": "Volume EM connectomics",
      "group": {
        "id": "microscopy-exvivo",
        "name": "Microscopy & ex vivo"
      },
      "mode": "read",
      "core": true,
      "summary": {
        "value": "Volume electron microscopy is electron imaging of fixed, heavy-metal-stained tissue, serial section by serial section, stitched into a three-dimensional volume; the short wavelength of electrons resolves synapses. What it reads is structure: electron-image contrast from the stain, from which cell shapes, synapses and the wiring between cells are reconstructed; it records no voltage or spikes. In a cubic millimetre of human temporal cortex resected during epilepsy surgery, 5019 sections about 34 nm thick were imaged at 4 nm pixels, and a classifier detected about 150 million synapses.",
        "node": "01a151cc-65fd-7e71-9afb-ff69f9af7082",
        "sources": [
          {
            "node": "01a15171-bc03-7380-90af-143295463bbd",
            "kind": "doi",
            "id": "10.1126/science.adk4858",
            "url": "https://doi.org/10.1126/science.adk4858"
          }
        ]
      },
      "row_node": "01a169ae-29b1-7fa0-8586-020f192331bd",
      "description": {
        "state": "known",
        "value": {
          "text": "Volume electron microscopy resolves dense neural tissue at the synaptic level because the short wavelength of electrons gives extremely high spatial resolution. This makes reconstruction of every cellular element and synapse possible in dense central nervous system networks. In the scoped human example, excess anterior middle temporal gyrus tissue resected during treatment for drug-resistant epilepsy undergoes rapid immersion fixation, which preserves ultrastructure. It is then further preserved and stained with osmium and other heavy metals under a ROTO staining protocol. The stained sample is embedded in resin, trimmed, and cut into thin serial sections that an automatic tape-collecting ultramicrotome collects. A multibeam scanning electron microscope images each section as tiles, and a workflow manager assesses each tile for quality during acquisition and flags problems. Cutting compresses sections in the cutting direction, and a pixel-size correction adjusts for this compression. Stitching and coarse alignment of tiles use microscope stage coordinates, semi-automated feature correspondences, and image patch cross-correlations that relax an elastic triangular mesh of each tile and each section. A fine-scale alignment based on optical flow between neighboring sections removes remaining drift and jitter. Tiles containing cortex combine into a unified image volume of human cerebral cortex."
        },
        "node": "01a151ba-56ae-7b72-a31e-36f94dd4e5c8",
        "sources": [
          {
            "node": "01a15171-bc03-7380-90af-143295463bbd",
            "kind": "doi",
            "id": "10.1126/science.adk4858",
            "url": "https://doi.org/10.1126/science.adk4858"
          }
        ]
      },
      "spatial_resolution_m": {
        "state": "known",
        "value": {
          "min": 2.7e-9,
          "max": 3.5e-9,
          "unit": "m",
          "note": "Step-edge resolution of FIB-SEM, not a FWHM: 2.7 nm as the 50% rise distance at a step edge at 0.08 nA beam current (5.5 nm at 4.0 nA), and below 3.5 nm by a 25–75% step-edge rise criterion in Drosophila brain imaged at 4 × 4 × 4 nm^3 voxels, where the hollow core of microtubules was resolved. In human serial-section multibeam SEM the figures are sampling: 4 nm pixels in-plane and 30–34 nm sections axially, so axial resolution depends on the method.",
          "operating_points": [
            {
              "label": "FIB-SEM, 50% step-edge rise at 0.08 nA",
              "min": 2.7e-9,
              "max": 2.7e-9,
              "note": "5.5 nm at 4.0 nA."
            },
            {
              "label": "FIB-SEM, Drosophila brain, 25–75% step-edge rise",
              "max": 3.5e-9,
              "note": "Resolved hollow microtubule core at 4 × 4 × 4 nm^3 voxels."
            },
            {
              "label": "Human serial-section multibeam SEM: nominal in-plane pixel",
              "min": 4e-9,
              "max": 4e-9,
              "note": "Acquired pixel size, 4 x 4 nm^2, before compression correction.",
              "endpoint": "sampling"
            },
            {
              "label": "Human serial-section multibeam SEM: corrected in-plane pitch, cutting direction",
              "min": 5.55e-9,
              "max": 5.55e-9,
              "note": "Corrected for 28% section compression along the cutting direction.",
              "endpoint": "sampling"
            },
            {
              "label": "Human serial-section multibeam SEM: corrected in-plane pitch, orthogonal direction",
              "min": 4e-9,
              "max": 4e-9,
              "note": "Direction perpendicular to cutting, uncorrected.",
              "endpoint": "sampling"
            },
            {
              "label": "Human serial-section multibeam SEM: axial section thickness, average",
              "min": 3.39e-8,
              "max": 3.39e-8,
              "note": "Average thickness across 5019 ATUM sections.",
              "endpoint": "sampling"
            },
            {
              "label": "Human serial-section multibeam SEM: axial section thickness, typical band",
              "min": 3e-8,
              "max": 3.3e-8,
              "note": "92.5% of sections fall between 30 and 33 nm.",
              "endpoint": "sampling"
            }
          ]
        },
        "node": "01a15cf2-5591-7ba3-9719-4dd8e13efcd2",
        "sources": [
          {
            "node": "01a15171-bc03-7380-90af-143295463bbd",
            "kind": "doi",
            "id": "10.1126/science.adk4858",
            "url": "https://doi.org/10.1126/science.adk4858"
          },
          {
            "node": "01a15196-a08b-7ba2-98d9-3eccaf49c2f6",
            "kind": "doi",
            "id": "10.7554/eLife.25916",
            "url": "https://doi.org/10.7554/eLife.25916"
          }
        ]
      },
      "temporal_resolution_s": {
        "state": "unknown",
        "value": {
          "reason": "In this protocol, excess human anterior middle temporal gyrus tissue resected during drug-resistant epilepsy treatment undergoes rapid immersion fixation, osmium/ROTO heavy-metal staining and resin embedding before ATUM sectioning and multibeam SEM imaging. The measured quantities are anatomical: electron-image contrast, ultrastructure, 3D cellular geometry, and synapses classified excitatory or inhibitory with inferred partners, with no voltage or spike recording. Neural event timing is therefore not a measured quantity, and the 326-day imaging time is acquisition duration, not a temporal resolution of neural activity."
        },
        "node": "01a151bc-7b76-75f1-9662-09a98387650d",
        "sources": [
          {
            "node": "01a15171-bc03-7380-90af-143295463bbd",
            "kind": "doi",
            "id": "10.1126/science.adk4858",
            "url": "https://doi.org/10.1126/science.adk4858"
          }
        ]
      },
      "field_of_view_m3": {
        "state": "known",
        "value": {
          "min": 1.05e-9,
          "max": 1.05e-9,
          "unit": "m3",
          "note": "Human surgically resected excess tissue from anterior middle temporal gyrus (drug-resistant epilepsy treatment), immersion fixed, ROTO heavy-metal stained, resin embedded. 5019 sections at average 33.9 nm give a total sample thickness of 0.170 mm. Multibeam SEM at 4 × 4 nm^2, with pixel size corrected to 5.55 × 4 nm for 28% cutting compression, gives a total imaged volume of 1.05 mm^3 of uncompressed tissue. This is a fixed-tissue structural nanoscale reconstruction of a cortical fragment, with imaging time of 326 days, and is not a living or whole-brain recording.",
          "endpoint": "acquired_volume"
        },
        "node": "01a151bc-f8a2-79e2-8bf2-7f70af2223ff",
        "sources": [
          {
            "node": "01a15171-bc03-7380-90af-143295463bbd",
            "kind": "doi",
            "id": "10.1126/science.adk4858",
            "url": "https://doi.org/10.1126/science.adk4858"
          }
        ]
      },
      "field_of_view_neurons": {
        "state": "known",
        "value": {
          "min": 82247.0,
          "max": 82247.0,
          "unit": "neuron",
          "note": "Mouse visual cortex, cubic-millimetre-scale serial-section EM dataset: a nucleus-feature classifier (96.9% precision, 99.6% recall against manual calls) predicted 82,247 neurons in the larger subvolume, which holds about 65% of the sections. The whole reconstruction contains more than 200,000 cells.",
          "endpoint": "acquired_volume",
          "operating_points": [
            {
              "label": "Human temporal cortex, 1.05 mm^3",
              "min": 16087.0,
              "max": 16087.0,
              "note": "Neurons manually identified among nucleated cells in surgically resected tissue.",
              "endpoint": "acquired_volume"
            },
            {
              "label": "Human: Spiny neurons",
              "min": 10531.0,
              "max": 10531.0,
              "note": "65.5% of neurons; 8,803 of these have a pyramidal shape.",
              "endpoint": "acquired_volume"
            },
            {
              "label": "Human: Spiny pyramidal-shaped neurons",
              "min": 8803.0,
              "max": 8803.0,
              "note": "Subset of the spiny neurons.",
              "endpoint": "acquired_volume"
            },
            {
              "label": "Human: Non-spiny neurons (interneurons)",
              "min": 4688.0,
              "max": 4688.0,
              "note": "29.1% of neurons, classified as interneurons.",
              "endpoint": "acquired_volume"
            },
            {
              "label": "Human: Unclassified neurons",
              "min": 868.0,
              "max": 868.0,
              "note": "5.4% of neurons that do not easily fit the spiny/non-spiny categorization, mostly because their somata are not fully in the volume.",
              "endpoint": "acquired_volume"
            }
          ]
        },
        "node": "01a16639-1cee-7d12-bdcc-9f30b98bf620",
        "sources": [
          {
            "node": "01a054da-6af8-70e1-bcea-4163be06fab2",
            "kind": "doi",
            "id": "10.1038/s41586-025-08790-w",
            "url": "https://doi.org/10.1038/s41586-025-08790-w"
          },
          {
            "node": "01a15171-bc03-7380-90af-143295463bbd",
            "kind": "doi",
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            "url": "https://doi.org/10.1126/science.adk4858"
          },
          {
            "node": "01a15195-c83a-71f3-aac8-f5e2c4aec704",
            "kind": "doi",
            "id": "10.1038/s41586-025-08790-w",
            "url": "https://doi.org/10.1038/s41586-025-08790-w"
          }
        ]
      },
      "measurand": {
        "state": "known",
        "value": {
          "measurands": [
            "heavy-metal-stained electron-image contrast",
            "ultrastructure",
            "3D cellular geometry and segmentation",
            "automatically detected synapses classified excitatory or inhibitory",
            "inferred synaptic connectivity between pre- and postsynaptic partners"
          ],
          "note": "In one rapidly immersion-fixed, osmium/ROTO-stained, resin-embedded sample of human anterior middle temporal gyrus resected during drug-resistant epilepsy treatment, 5019 ATUM sections averaging 33.9 nm thick are imaged by multibeam SEM at 4 x 4 nm, corrected to 5.55 x 4 nm for 28% cutting compression, giving 1.05 mm^3. Stitched, aligned images yield segmented neurons with residual split and merge errors that require proofreading. A U-Net classifier identifies ~150M synapses (~111M excitatory, ~39M inhibitory) with layer-wise densities and assigns them to partners, giving excitatory and inhibitory input maps per cell. These are anatomical counts and classifications of synaptic contacts, with no voltage or spike recording."
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          "text": "A macroscope illuminates the dorsal cortex with blue light and records GCaMP fluorescence with a camera while the mouse is head-fixed. Clear dental cement and a coverslip make the intact skull suitable for chronic imaging; the demonstrated window spans about 11 × 9 mm across both hemispheres. The images follow cortical calcium activity across regions. Fluorescence mixes contributions from different tissue depths, and scattering broadens the signal, so camera pixels do not identify individual neurons."
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          "note": "In the intact-skull implementation, imaging is external to the brain: the scalp is removed and the skull is gently cleaned and covered with transparent cement and glass, while the skull and brain remain intact. This category concerns brain tissue, not the absence of surgery or a guarantee against harm."
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