4.8 Article

Functional ultrasound localization microscopy reveals brain-wide neurovascular activity on a microscopic scale

Journal

NATURE METHODS
Volume 19, Issue 8, Pages 1004-+

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41592-022-01549-5

Keywords

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Funding

  1. AXA Research Fund (AXA Chair New Hopes in Medical Imaging with Ultrasound)
  2. INSERM Accelerator of Technological Research in Biomedical Ultrasound
  3. NVIDIA Corporation

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Ultrasound localization microscopy (ULM) is a technique that allows localization and monitoring of cerebral blood flow at a small scale. By detecting the flow of injected microbubbles, ULM provides real-time information about brain activity at high spatiotemporal resolution.
The advent of neuroimaging has increased our understanding of brain function. While most brain-wide functional imaging modalities exploit neurovascular coupling to map brain activity at millimeter resolutions, the recording of functional responses at microscopic scale in mammals remains the privilege of invasive electrophysiological or optical approaches, but is mostly restricted to either the cortical surface or the vicinity of implanted sensors. Ultrasound localization microscopy (ULM) has achieved transcranial imaging of cerebrovascular flow, up to micrometre scales, by localizing intravenously injected microbubbles; however, the long acquisition time required to detect microbubbles within microscopic vessels has so far restricted ULM application mainly to microvasculature structural imaging. Here we show how ULM can be modified to quantify functional hyperemia dynamically during brain activation reaching a 6.5-mu m spatial and 1-s temporal resolution in deep regions of the rat brain. Functional ultrasound localization microscopy monitors cerebrovascular blood flow by detecting the flow of injected microbubbles, providing access to brain activity at high spatiotemporal resolution.

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