Ultrafast ultrasonic imaging is a rapidly developing field based on the unfocused transmission of plane or diverging ultrasound waves. This recent approach to ultrasound imaging leads to a large increase in raw ultrasound data available per acquisition. Bigger synchronous ultrasound imaging datasets can be exploited in order to strongly improve the discrimination between tissue and blood motion in the field of Doppler imaging. Here we propose a spatiotemporal singular value decomposition clutter rejection of ultrasonic data acquired at ultrafast frame rate. The singular value decomposition (SVD) takes benefits of the different features of tissue and blood motion in terms of spatiotemporal coherence and strongly outperforms conventional clutter rejection filters based on high pass temporal filtering. Whereas classical clutter filters operate on the temporal dimension only, SVD clutter filtering provides up to a four-dimensional approach (3D in space and 1D in time). We demonstrate the performance of SVD clutter filtering with a flow phantom study that showed an increased performance compared to other classical filters (better contrast to noise ratio with tissue motion between 1 and 10mm/s and axial blood flow as low as 2.6 mm/s). SVD clutter filtering revealed previously undetected blood flows such as microvascular networks or blood flows corrupted by significant tissue or probe motion artifacts. We report in vivo applications including small animal fUltrasound brain imaging (blood flow detection limit of 0.5 mm/s) and several clinical imaging cases, such as neonate brain imaging, liver or kidney Doppler imaging.

We developed an integrated experimental framework which extends the brain exploration capabilities of functional ultrasound imaging to awake/mobile animals. In addition to hemodynamic data, this method further allows parallel access to EEG recordings of neuronal activity. This approach is illustrated with two proofs of concept: first, a behavioral study, concerning theta rhythm activation in a maze running task and, second, a disease-related study concerning spontaneous epileptic seizures.In vivo brain activity recordings provide a unique contribution to neuroscience to unravel the underlying mechanisms of complex behaviors and pathologies. Ideally we would like to capture instantly both neuronal activity and metabolic events, which form two major facets of global brain equilibrium, in the most natural conditions, that is when the subject is awake and freely moving. There is an increasing awareness today that major issues of neurophysiology need to be addressed with such global approaches. Notably, the basic mechanisms involved in functional network dynamics and pathologies including epilepsy can be deciphered only if the electrographic and metabolic components are sensed concomitantly [Logothetis 2008, Sada 2015. More generally, the multiple feedbacks between electrographic and metabolic signals represent the rule, rather than the exception. They have been tackled separately only by lack of appropriate methods for accessing the global picture, prompting the development of multimodal strategies.In practice there is a compromise between the size of imaging field, time resolution, sensitivity, separability of processing and metabolism, and physical constraint on the animal.Corresponding author: IC, ivan.cohen@upmc.fr. Author contributions LAS designed the surgical procedure and prosthetic skull, and performed and analyzed epilepsy experiments; AB designed intrahippocampal recording procedure and performed and analyzed navigation experiments; ET and TD developed the "burst mode" ultrasound recording sequence; MP and JLG developed the "continuous mode" ultrasound recording sequence; JLG and MT designed and supervised the ultrasound scanner and probe; IC designed and supervised the experiments, designed the probe holder, programmed acquisition and analysis software; IC, LAS, AB wrote the paper.

Rapid eye movement sleep (REMS) is a peculiar brain state combining the behavioral components of sleep and the electrophysiological profiles of wake. After decades of research our understanding of REMS still is precluded by the difficulty to observe its spontaneous dynamics and the lack of multimodal recording approaches to build comprehensive datasets. We used functional ultrasound (fUS) imaging concurrently with extracellular recordings of local field potentials (LFP) to reveal brain-wide spatiotemporal hemodynamics of single REMS episodes. We demonstrate for the first time the close association between global hyperemic events – largely outmatching wake levels in most brain regions – and local hippocampal theta (6–10 Hz) and fast gamma (80–110 Hz) events in the CA1 region. In particular, the power of fast gamma oscillations strongly correlated with the amplitude of subsequent vascular events. Our findings challenge our current understanding of neurovascular coupling and question the evolutionary benefit of such energy-demanding patterns in REMS function.