Changes in cerebral blood flow are associated with stroke, aneurysms, vascular cognitive impairment, neurodegenerative diseases and other pathologies. Brain angiograms, typically performed via computed tomography or magnetic resonance imaging, are limited to millimetre-scale resolution and are insensitive to blood-flow dynamics. Here, we show that ultrafast ultrasound localization microscopy of intravenously injected microbubbles enables transcranial imaging of deep vasculature in the adult human brain at microscopic resolution and the quantification of haemodynamic parameters. Adaptive speckle tracking to correct for micrometric brain-motion artefacts and for ultrasonic-wave aberrations induced during transcranial propagation allowed us to map the vascular network of tangled arteries, to functionally characterize blood-flow dynamics at a resolution of up to 25 μm, and to detect blood vortices in a small deep-seated aneurysm in a patient. Ultrafast ultrasound localization microscopy may facilitate the understanding of brain haemodynamics and of how vascular abnormalities in the brain are related to neurological pathologies.
Medical ultrasound is a widely used diagnostic imaging technique for tissues and blood vessels. However, its spatial resolution is limited to a sub-millimeter scale. Ultrasound Localization Microscopy was recently introduced to overcome this limit and relies on subwavelength localization and tracking of microbubbles injected in the blood circulation. Yet, as microbubbles follow blood flow, long acquisition time are required to detect them in the smallest vessels, leading to long reconstruction of the microvasculature. The objective of this work is to understand how blood flow limits acquisition time. We studied the reconstruction of a coronal slice of a rat’s brain during a continuous microbubble injection close to clinical concentrations. After acquiring 192000 frames over 4 minutes, we find that the biggest vessels can be reconstructed in seconds but that it would take tens of minutes to map the entire capillary network. Moreover, the appropriate characterization of flow profiles based on microbubble velocity within vessels is bound by even more stringent temporal limitations. As we use simple blood flow models to characterize its impact on reconstruction time, we foresee that these results and methods can be adapted to determine adequate microbubble injections and acquisition times in clinical and preclinical practice.
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