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.
germline genetic engineering: GCaMP mice: transgenic GCaMP6f/6s-expressing mice imaged through intact skin and skull.; other: GCaMP mice: a 100 μm black microsphere placed just above the skin for per-pulse laser energy normalization.; anesthesia: Rat: maintained under 1.5% vaporized isoflurane, with ophthalmic ointment over the eyes.; surgery: 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.; surgery: Rat functional imaging: top part of the scalp removed with the skull kept intact.; other: Rat: 3D-printed nose cone and tooth bar placed, with the gap sealed by silicone glue.; anesthesia: Fiber-transducer BALB/c mice: 1.5% isoflurane in air (~0.5 L/min), reduced to 0.75% during imaging.; surgery: Fiber-transducer mice: hair removed; skull thinned from 1–3 mm posterior to bregma, 8 mm wide, centered on the superior sagittal sinus.; other: 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.; surgery: PanoPACT: ~8 mm diameter portion of parietal bone removed without damaging the dura; scalp sutured without replacement.; other: PanoPACT: low-dose mannitol to alleviate brain swelling; brain centered in the array, with the mask–nose interface sealed by parafilm.; other: 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.
Description
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.