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The quest to decode the complex supraspinal mechanisms that integrate cutaneous thermal information in the central system is still ongoing. The dorsal horn of the spinal cord is the first hub that encodes thermal input which is then transmitted to brain regions via the spinothalamic and thalamocortical pathways. So far, our knowledge about the strength of the interplay between the brain regions during thermal processing is limited. To address this question, we imaged the brains of adult awake male mice in resting state using functional ultrasound imaging during plantar exposure to constant and varying temperatures. Our study reveals for the first time the following: (1) a dichotomy in the response of the somatomotor-cingulate cortices and the hypothalamus, which was never described before, due to the lack of appropriate tools to study such regions with both good spatial and temporal resolutions. (2) We infer that cingulate areas may be involved in the affective responses to temperature changes. (3) Colder temperatures (ramped down) reinforce the disconnection between the somatomotor-cingulate and hypothalamus networks. (4) Finally, we also confirm the existence in the mouse brain of a brain mode characterized by low cognitive strength present more frequently at resting neutral temperature. The present study points toward the existence of a common hub between somatomotor and cingulate regions, whereas hypothalamus functions are related to a secondary network. [ABSTRACT FROM AUTHOR]

In vivo assessment of dispersion affecting the propagation of visco-elastic waves in soft tissues is key to understand the rheology of human tissues. In this paper, the ability of the supersonic shear imaging (SSI) technique to generate planar shear waves propagating in tissues is fully exploited. First, by strongly limiting shear wave diffraction in the imaging plane, this imaging technique enables to discriminate between the usually concomitant influences of both medium rheological properties and diffraction affecting the shear wave dispersion. Second, transient propagation of these plane shear waves in soft tissues can be measured using echographic images acquired at very high frame. In vitro and in vivo experiments demonstrate that dispersion curves, which characterize the rheological behavior of tissues by measuring the frequency dependence of shear wave speed and attenuation, can be recovered in the 75-600 Hz frequency range. Based on a phase difference algorithm, the dispersion curves are computed in 1 [cm.sup.2] regions of interest from the acquired propagation movie. In vivo measurements in Biceps Brachii muscle and liver of three healthy volunteers show important differences in the rheological behavior of these different tissues. Liver tissue appears to be much more dispersive with a phase velocity ranging from ~ 1.5 m/s at 75 Hz to ~ 3 m/s at 500 Hz whereas muscle tissue shows an important anisotropy, shear waves propagating longitudinally to the muscular fibers are almost nondispersive while those propagating transversally are very dispersive with a shear wave speed ranging from 0.5 to 2 m/s between 75 and 500 Hz. The estimation of dispersion curves is local and can be performed separately in different regions of the organ. This signal processing approach based on the SSI modality introduces the new concept of in vivo shear wave spectroscopy (SWS) that could become an additional tool for tissue characterization. This paper demonstrates the in vivo ability of this SWS to quantify both local shear elasticity and dispersion in real time. Index Terms--Dispersion, elastography, liver, muscle, rheology, shear wave spectroscopy (SWS), supersonic shear imaging (SSI).

Spreading depolarization (SD), usually termed cortical spreading depression has been proposed as the pathophysiological substrate of migraine aura and as an endogenous trigger of headache pain. The links between neurovascular coupling and cortical craniofacial nociceptive activities modulated by SD were assessed by combining in vivo local field potential (LFPs) recordings in the primary somatosensory cortex (S1) with functional ultrasound (fUS) imaging of S1 and caudal insular (INS) cortices of anesthetized male rats. A single SD wave triggered in the primary visual cortex elicited an ipsilateral, quadriphasic hemodynamic and electrophysiological response in S1 with an early phase consisting of concomitant increases of relative cerebral blood volume (rCBV) and LFPs. A transient hypoperfusion was then correlated with the beginning of the neuronal silence, followed by a strong increase of rCBV while synaptic activities remained inhibited.LFPs and rCBV recovery period was followed by a progressive increase in S1 and INS baseline activities and facilitation of cortical responses evoked by periorbital cutaneous receptive fields stimulation. Sensitization of cortical ophthalmic fields by SD was bilateral, occurred with precise spatiotemporal profiles and was significantly reduced by pre-treatment with a NMDA antagonist. Combined high-resolution assessing of neurovascular coupling and electrophysiological activities has revealed a useful preclinical tool for deciphering central sensitization mechanisms involved in migraine attacks. [ABSTRACT FROM AUTHOR]

The article presents a new approach called the echo mechanomypgraphy, where in the two-dimensional (2-D) and three-dimensional (3-D) very high frame rate ultrasound imaging is employed to study the mechanical properties of the musculoskeletal system. The approach is shown to be widely used for the noninvasive muscle diagnosis of an active contractile tissue.

In both human and nonhuman primates (NHP), the medial prefrontal region, defined as the supplementary eye field (SEF), can indirectly influence behavior selection through modulation of the primary selection process in the oculomotor structures. To perform this oculomotor control, SEF integrates multiple cognitive signals such as attention, memory, reward, and error. As changes in pupil responses can assess these cognitive efforts, a better understanding of the precise dynamics by which pupil diameter and medial prefrontal cortex activity interact requires thorough investigations before, during, and after changes in pupil diameter. We tested whether SEF activity is related to pupil dynamics during a mixed pro/antisaccade oculomotor task in 2 macaque monkeys. We used functional ultrasound (fUS) imaging to examine temporal changes in brain activity at the 0.1-s time scale and 0.1-mm spatial resolution concerning behavioral performance and pupil dynamics. By combining the pupil signals and real-time imaging of NHP during cognitive tasks, we were able to infer localized cerebral blood volume (CBV) responses within a restricted part of the dorsomedial prefrontal cortex, referred to as the SEF, an area in which antisaccade preparation activity is also recorded. Inversely, SEF neurovascular activity measured by fUS imaging was found to be a robust predictor of specific variations in pupil diameter over short and long-time scales. Furthermore, we directly manipulated pupil diameter and CBV in the SEF using reward modulations. These results bring a novel understanding of the physiological links between pupil and SEF, but it also raises questions about the role of anterior cingulate cortex (ACC), as CBV variations in the ACC seems to be negligible compared to CBV variations in the SEF. Ultrafast functional imaging reveals short- and long-term covariations between pupil diameter and activity in the Supplementary Eye Field (SEF) of awake behaving non-human primates, yielding a novel understanding of the physiological links between the pupil and SEF. [ABSTRACT FROM AUTHOR]

Aims Hepatic capillaries are lined with specialized liver sinusoidal endothelial cells (LSECs) which support macromolecule passage to hepatocytes and prevent fibrosis by keeping hepatic stellate cells (HSCs) quiescent. LSEC specialization is co-determined by transcription factors. The zinc-finger E-box-binding homeobox (Zeb)2 transcription factor is enriched in LSECs. Here, we aimed to elucidate the endothelium-specific role of Zeb2 during maintenance of the liver and in liver fibrosis. Methods and results To study the role of Zeb2 in liver endothelium we generated EC-specific Zeb2 knock-out (ECKO) mice. Sequencing of liver EC RNA revealed that deficiency of Zeb2 results in prominent expression changes in angiogenesis-related genes. Accordingly, the vascular area was expanded and the presence of pillars inside ECKO liver vessels indicated that this was likely due to increased intussusceptive angiogenesis. LSEC marker expression was not profoundly affected and fenestrations were preserved upon Zeb2 deficiency. However, an increase in continuous EC markers suggested that Zeb2-deficient LSECs are more prone to dedifferentiation, a process called 'capillarization'. Changes in the endothelial expression of ligands that may be involved in HSC quiescence together with significant changes in the expression profile of HSCs showed that Zeb2 regulates LSEC–HSC communication and HSC activation. Accordingly, upon exposure to the hepatotoxin carbon tetrachloride (CCl4), livers of ECKO mice showed increased capillarization, HSC activation, and fibrosis compared to livers from wild-type littermates. The vascular maintenance and anti-fibrotic role of endothelial Zeb2 was confirmed in mice with EC-specific overexpression of Zeb2, as the latter resulted in reduced vascularity and attenuated CCl4-induced liver fibrosis. Conclusion Endothelial Zeb2 preserves liver angioarchitecture and protects against liver fibrosis. Zeb2 and Zeb2-dependent genes in liver ECs may be exploited to design novel therapeutic strategies to attenuate hepatic fibrosis. [ABSTRACT FROM AUTHOR]

Row column addressing (RCA) transducers have the potential to provide volumetric imaging at ultrafast frame rate using a low channel count over a large field of view. In previous works we have shown that vascular imaging of large arteries as well as functional neuroimaging of the rat brain were feasible using RCA orthogonal plane wave imaging (OPW), but these applications required to transmit many plane waves, significantly reducing the frame rate. In this study, we introduce XDoppler imaging, a novel method to increase the performances of RCA flow imaging by taking advantage of the blood spatial decorrelation statistics combined with the limited spatial overlap of the point spread functions (PSF) of the two orthogonal apertures of the RCA transducer. We provide at first a theoretical basis to understand how the correlation operation reduces the sidelobe level. Then, we demonstrate both in vitro and in vivo in the human carotid artery and in the rat brain that XDoppler provides a significant gain in contrast-to-noise ratio (CNR) (between 3 and 6 dB depending on the application) compared to OPW. This improvement also leads to a sensitivity increase in the rat brain as more blood vessels are detected by XDoppler imaging. [ABSTRACT FROM AUTHOR]

• As fMRI, functional ultrasound imaging (fUS) is based on neurovascular coupling. • fUS has a high spatio temporal resolution and sensitivity. • fUS portability allows imaging in awake animals. • fUS is promising for human neonates or per-operative surgery imaging. Ultrasound sensitivity to slow blood flow motion gained two orders of magnitude in the last decade thanks to the advent of ultrafast ultrasound imaging at thousands of frames per second. In neuroscience, this access to small cerebral vessels flow led to the introduction of ultrasound as a new and full-fledged neuroimaging modality. Much as functional MRI or functional optical imaging, functional Ultrasound (fUS) takes benefit of the neurovascular coupling. Its ease of use, portability, spatial and temporal resolution makes it an attractive tool for functional imaging of brain activity in preclinical imaging. A large and fast-growing number of studies in a wide variety of small to large animal models have demonstrated its potential for neuroscience research. Beyond preclinical imaging, first proof of concept applications in humans are promising and proved a clear clinical interest in particular in human neonates, per-operative surgery, or even for the development of non-invasive brain machine interfaces. [ABSTRACT FROM AUTHOR]

The rise of ultrafast ultrasound imaging—with plane or diverging waves - paved the way to new applications of ultrasound in biomedical applications. However, propagation through complex layers (typically fat, muscle, and bone) hinder considerably the image quality, especially because of sound speed heterogeneities. In difficult-to-image patients, in the case of the hepatic steatosis for instance, a good image and a reliable sound speed quantification are crucial to provide a powerful non-invasive diagnosis tool. In this work, we proposed to adapt the singular value decomposition (SVD) beamformer method for diverging waves and thus present a novel aberration correction approach for widely used curved arrays. We probed its efficiency experimentally both in vitro and in vivo. Besides the proposed matrix formalism, we explored the physical meaning of the SVD of ultrafast data. Finally, we demonstrated the ability of the technique to improve the image quality and offer new perspectives particularly in quantitative liver imaging. [ABSTRACT FROM AUTHOR]

A shift of paradigm is currently underway in biomedical ultrasound thanks to plane or diverging waves coherent compounding for faster imaging. One remaining challenge consists in handling phase and amplitude aberrations induced during the ultrasonic propagation through complex layers. Unlike conventional line-per-line imaging, ultrafast ultrasound provides backscattering information from the whole imaged area for each transmission. Here, we take benefit from this feature and propose an efficient approach to perform fast aberration correction. Our method is based on the Singular Value Decomposition (SVD) of an ultrafast compound matrix containing backscattered data for several plane wave transmissions. First, we explain the physical signification of SVD and associated singular vectors within the ultrafast matrix formalism. We theoretically demonstrate that the separation of spatial and angular variables, rendered by SVD on ultrafast data, provides an elegant and straightforward way to optimize the angular coherence of backscattered data. In heterogeneous media, we demonstrate that the first spatial and angular singular vectors retrieve respectively the non-aberrated image of a region of interest, and the phase and amplitude of its aberration law. Numerical, in vitro and in vivo results prove the efficiency of the image correction, but also the accuracy of the aberrator determination. Based on spatial and angular coherence, we introduce a complete methodology for adaptive beamforming of ultrafast data, performed on successive isoplanatism patches undergoing SVD beamforming. The simplicity of this method paves the way to real-time adaptive ultrafast ultrasound imaging and provides a theoretical framework for future quantitative ultrasound applications. [ABSTRACT FROM AUTHOR]

Functional ultrasound imaging (fUS) recently emerged as a promising neuroimaging modality to image and monitor brain activity based on cerebral blood volume response (CBV) and neurovascular coupling. fUS offers very good spatial and temporal resolutions compared to fMRI gold standard as well as simplicity and portability. It was recently extended to 4D fUS imaging in preclinical settings although this approach remains limited and complex. Indeed 4D fUS requires a 2D matrix probe and specific hardware able to drive the N2 elements of the probe with thousands of electronic channels. Several under-sampling approaches are currently investigated to limit the channel count and spread ultrasound 4D modalities. Among them, the Row Column Addressing (RCA) approach combined with ultrafast imaging is a compelling alternative using only N + N channels. We present a large field of view RCA probe prototype of 128 + 128 channels and 15 MHz central frequency adapted for preclinical imaging. Based on the Orthogonal Plane Wave compounding scheme, we were able to perform 4D vascular brain acquisitions at high volume rate. Doppler volumes of the whole rat brain were obtained in vivo at high rates (23 dB CNR at 156 Hz and 19 dB CNR at 313 Hz). Visual and whiskers stimulations were performed and the corresponding CBV increases were reconstructed in 3D with successful functional activation detected in the superior colliculus and somato-sensorial cortex respectively. This proof of concept study demonstrates for the first time the use of a low-channel count RCA array for in vivo 4D fUS imaging in the whole rat brain. [ABSTRACT FROM AUTHOR]

For successful brain therapy, transcranial focused ultrasound must compensate for the time shifts induced locally by the skull. The patient-specific phase profile is currently generated by multi-element arrays which, over time, have tended toward increasing element count. We recently introduced a new approach, consisting of a single-element transducer coupled to an acoustic lens of controlled thickness. By adjusting the local thickness of the lens, we were able to induce phase differences which compensated those induced by the skull. Nevertheless, such an approach suffers from an apparent limitation: the lens is a priori designed for one specific target. In this paper, we demonstrate the possibility of taking advantage of the isoplanatic angle of the aberrating skull in order to steer the focus by mechanically moving the transducer/acoustic lens pair around its initial focusing position. This study, conducted on three human skull samples, demonstrates that tilting of the transducer with the lens restores a single −3 dB focal volume at 914 kHz for a steering up to ±11 mm in the transverse direction, and ±10 mm in the longitudinal direction, around the initial focal region. [ABSTRACT FROM AUTHOR]