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.

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This is the second article in a series of two which report on a matrix approach for ultrasound imaging in heterogeneous media. This article describes the quantification and correction of aberration, i.e. the distortion of an image caused by spatial variations in the medium speed-of-sound. Adaptive focusing can compensate for aberration, but is only effective over a restricted area called the isoplanatic patch. Here, we use an experimentally-recorded matrix of reflected acoustic signals to synthesize a set of virtual transducers. We then examine wave propagation between these virtual transducers and an arbitrary correction plane. Such wave-fronts consist of two components: (i) An ideal geometric wave-front linked to diffraction and the input focusing point, and; (ii) Phase distortions induced by the speed-of-sound variations. These distortions are stored in a so-called distortion matrix, the singular value decomposition of which gives access to an optimized focusing law at any point. We show that, by decoupling the aberrations undergone by the outgoing and incoming waves and applying an iterative strategy, compensation for even high-order and spatially-distributed aberrations can be achieved. After a numerical validation of the process, ultrasound matrix imaging (UMI) is applied to the in-vivo imaging of a gallbladder. A map of isoplanatic modes is retrieved and is shown to be strongly correlated with the arrangement of tissues constituting the medium. The corresponding focusing laws yield an ultrasound image with drastically improved contrast and transverse resolution. UMI thus provides a flexible and powerful route towards computational ultrasound.

Precision targeting and monitoring of preclinical focused ultrasound enabled by fluorescence-guided transcranial ultrasound.

Ultrasound can be delivered transcranially to ablate brain tissue, open the blood-brain barrier, or affect neural activity. Transcranial focused ultrasound in small rodents is typically done with lowfrequency single-element transducers, which results in unspecific targeting and impedes the concurrent use of fast neuroimaging methods. In this article, we devised a wide-angle spherical array bidirectional interface for high-resolution parallelized optoacoustic imaging and transcranial ultrasound (POTUS) delivery in the same target regions. The system operates between 3 and 9 MHz, allowing to generate and steer focal spots with widths down to 130 m across a field of view covering the entire mouse brain, while the same array is used to capture high-resolution 3-D optoacoustic data in real time. We showcase the system's versatile beam-forming capacities as well as volumetric optoacoustic imaging capabilities and discuss its potential to noninvasively monitor brain activity and various effects of ultrasound emission.

This is the first article in a series of two dealing with a matrix approach for aberration quantification and correction in ultrasound imaging. Advanced synthetic beamforming relies on a double focusing operation at transmission and reception on each point of the medium. Ultrasound matrix imaging (UMI) consists in decoupling the location of these transmitted and received focal spots. The response between those virtual transducers form the so-called focused reflection matrix that actually contains much more information than a confocal ultrasound image. In this paper, a time-frequency analysis of this matrix is performed, which highlights the single and multiple scattering contributions as well as the impact of aberrations in the monochromatic and broadband regimes. Interestingly, this analysis enables the measurement of the incoherent input-output point spread function at any pixel of this image. A fitting process enables the quantification of the single scattering, multiple scattering and noise components in the image. From the single scattering contribution, a focusing criterion is defined, and its evolution used to quantify the amount of aberration throughout the ultrasound image. In contrast to the state-of-the-art coherence factor, this new indicator is robust to multiple scattering and electronic noise, thereby providing a contrasted map of the focusing quality at a much better transverse resolution. After a validation of the proof-of-concept based on time-domain simulations, UMI is applied to the in-vivo study of a human calf. Beyond this specific example, UMI opens a new route for speed-of-sound and scattering quantification in ultrasound imaging.

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