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.

The strain rate effect on large strain dissipation and behavior recovery are presented to understand the toughening effect of silica nanoparticles in nanohybrid hydrogels. Such nanohybrid gels combine a poly(N,N-dimethylacrylamide) (PDMA) covalent network and physical interactions by adsorption of polymer chains at the silica nanoparticle surface. A series of model nanohybrid gels has been designed to obtain a well-controlled architecture. First insights on the structure (SANS) demonstrated that silica nanoparticles were welldispersed in the gel, including after cyclic mechanical loading. The characteristic times involved in the nanoparticle/polymer association were investigated by large strain mechanical cycling varying the strain rate from 3 × 10 −4 s −1 to 0.6 s −1 . The mechanical behavior of the hybrid hydrogel varies tremendously over a relatively small range of strain rates, ranging from almost non dissipative (at slow strain rates) to highly dissipative at high strain rates. However, upon cycling over time-scales of tens of seconds, the strong physical interactions taking place between nanosilica particles and PDMA network chains enabled the hydrogel to recover its initial mechanical properties. The main feature of this work is the remarkable role played by silica nanoparticles in the network to promote transient and recoverable connectivity by reversible adsorption/desorption processes. The strong strain rate dependence suggests that toughening mechanisms operating at standard strain rates as often reported, maybe quite different at slower or larger strain rates.

Neuroimaging modalities such as MRI and EEG are able to record from the whole brain, but this comes at the price of either limited spatiotemporal resolution or limited sensitivity. Here, we show that functional ultrasound imaging (fUS) of the brain is able to assess local changes in cerebral blood volume during cognitive tasks, with sufficient temporal resolution to measure the directional propagation of signals. In two macaques, we observed an abrupt transient change in supplementary eye field (SEF) activity when animals were required to modify their behaviour associated with a change of saccade tasks. SEF activation could be observed in a single trial, without averaging. Simultaneous imaging of anterior cingulate cortex and SEF revealed a time delay in the directional functional connectivity of 0.27 ± 0.07 s and 0.9 ± 0.2 s for both animals. Cerebral hemodynamics of large brain areas can be measured at high spatiotemporal resolution using fUS.

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Elucidating the developmental process of an organism will require the complete cartography of cellular lineages in the spatial, temporal, and molecular domains. We present Zebrahub, a comprehensive dynamic atlas of zebrafish embryonic development that combines single-cell sequencing time course data with light-sheet microscopy-based lineage reconstructions. Zebrahub is a foundational resource to study developmental processes at both transcriptional and spatiotemporal levels. It is publicly accessible as a web-based resource, providing an open-access collection of datasets and tools. Using this resource we shed new light on the pluripotency of Neuro-Mesodermal Progenitors (NMPs). We find that NMPs are pluripotent only during early axis elongation before becoming exclusively mesodermal progenitors. We attribute this restriction in NMP cell fate to emerging morphodynamic features that compartmentalize tissue motion.

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-µm spatial and 1-s temporal resolution in deep regions of the rat brain.

Perfusion parameter estimation from dynamic contrast-enhanced ultrasound (DCE-US) data relies on fitting parametric models of flow to curves describing linear echo power as a function of time. The least squares criterion is generally used to fit these models to data. This criterion is optimal in the sense of maximum likelihood under the assumption of an additive white Gaussian noise. In the current work, it is demonstrated that this assumption is not held for DCEUS. A better-adapted maximum likelihood criterion based on a multiplicative model is proposed. It is tested on simulated bolus perfusion data and on 11 sequences acquired in vivo during bolus perfusion of contrast agent in the cortex of healthy murine kidney, an area where the perfusion is expected to be approximately homogeneous. Results on simulated data show a significant improvement (p < 0.05) of the precision and the accuracy for the estimations of perfusion parameters time to peak (TTP), wash-in rate (WiR), and mean transit time (MTT). On the 11 in vivo sequences, the new method leads to a significant reduction (p < 0.05) in the variation of parametric maps for 9 sequences for TTP and 10 sequences for WiR and MTT. The mean percent decreases of the coefficient of variation are 40%, 25%, and 59% for TTP, WiR, and MTT, respectively. This method should contribute to a more robust and accurate estimation of perfusion parameters and an improved resolution of parametric imaging.

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