Ultrasound localization microscopy

Optical & ultrasound (in vivo) · reads

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.

Spatial resolution
16 µm (two-source)
Temporal resolution
1 s (recoverable timing)
Field of view
60.3 cm³ (acquired volume)
Reads
microbubble trajectories; blood-flow speed
Destructive?
non-destructive
Prerequisites
other: Place an intravenous cannula in the medial cubital vein.; contrast agent: Inject an ultrasound contrast agent through the cannula.
Theoretical spatial resolution
2 µm (localisation error)
Theoretical field of view
1.12–1.23 L (reachable envelope)

Description

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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