Ultrafast Doppler Research Articles

Development of an Imaging Framework for Visualization of Cutaneous Micro-Vasculature by using High Frequency Ultrafast Ultrasound Imaging.

Visualization of cutaneous micro-vasculatures is a determined approach in the diagnosis of skin vascular disorders. Clinically, high frequency ultrasound (HFUS) modalities have been used for cutaneous morphological and structural imaging, but visualization of micro-vessels has always been remained a daunting task. These tiny structures might be visualized by devising a highly sensitive Doppler technique for HFUS systems. In this study, we proposed an imaging framework using HFUS (30 MHz) ultrafast Doppler imaging along with SVD clutter filtering that is proficient in detection of micro-scale circulation. The performance of the devised framework was examined on a 200-micron flow phantom made of poly-vinyl alcohol under four different flow rates (56 - 18 ul/min) and visualized the micro-structure with averaged detected diameter of 93 - 170 µm. The results indicated that the devised framework has sufficient sensitivity and resolvability to visualize the micro-vasculatures in dermis layer of skin (depth ≤ 4 mm). Clinical Relevance - This study brings an insight to visualize in-vivo cutaneous micro-vasculatures with ultrafast Doppler imaging in clinical applications for better assessment of cutaneous disorders.

Improving coronary ultrafast Doppler angiography using fractional moving blood volume and motion-adaptive ensemble length

Coronary microperfusion assessment is a key parameter for understanding cardiac function. Currently, coronary ultrafast Doppler angiography is the only non-invasive clinical imaging technique able to assess coronary microcirculation quantitatively in humans. In this study, we propose to use fractional moving blood volume (FMBV), proportional to the red blood cell concentration, as a metric for perfusion. FMBV compares the power Doppler in a region of interest (ROI) inside the myocardium to the power Doppler of a reference area in the heart chamber, fully filled with blood. This normalization gives then relative values of the ROI blood filling. However, due to the impact of ultrasound attenuation and elevation focus on power Doppler values, the reference area and the ROI need to be at the same depth to allow this normalization. This condition is rarely satisfied in vivo due to the cardiac anatomy. Hereby, we propose to locally compensate the attenuation between the ROI and the reference, by measuring the attenuation law on a phantom. We quantified the efficiency of this approach by comparing FMBV with and without compensation on a flow phantom. Compensated FMBV was able to estimate the ground-truth FMBV with less than 5% variation. This method was then adapted to the in vivo case of myocardial perfusion imaging during heart surgery on human neonates. The translation from in vitro to in vivo required an additional clutter filtering step to ensure that blood signals could be correctly identified in the fast-moving myocardium. We applied the singular value decomposition filter on temporal sliding windows whose lengths were a function of myocardium motion. This motion-adaptive temporal sliding window approach was able to improve blood and tissue separation in terms of contrast-to-noise ratio, as compared to well-established constant-length sliding window approaches. Therefore, compensated FMBV and singular value decomposition assisted with motion-adaptive temporal sliding windows improves the quantification of blood volume in coronary ultrafast Doppler angiography.

Improved Ultrafast Power Doppler Imaging by Using Spatiotemporal Non-Local Means Filtering.

The change of microvasculature is associated with the occurrence and development of many diseases. Ultrafast power Doppler imaging (uPDI) is an emerging technology for the visualization of microvessels due to the development of ultrafast plane wave (PW) imaging and advanced clutter filters. However, the low signal-to-noise ratio (SNR) caused by unfocused transmit of PW imaging deteriorates the subsequent imaging of microvasculature. Nonlocal means (NLM) filtering has been demonstrated to be effective in the denoising of both natural and medical images, including ultrasound power Doppler images. However, the feasibility and performance of applying an NLM filter on the ultrasound radio frequency (RF) data have not been investigated so far. In this study, we propose to apply an NLM filter on the spatiotemporal domain of clutter filtered blood flow RF data (St-NLM) to improve the quality of uPDI. Experiments were conducted to compare the proposed method with three different methods (under various similarity window sizes), including conventional uPDI without NLM filtering (Non-NLM), NLM filtering on the obtained power Doppler images (PD-NLM), and NLM filtering on the spatial domain of clutter filtered blood flow RF data (S-NLM). Phantom experiments, in vivo contrast-enhanced human spinal cord tumor experiments, and in vivo contrast-free human liver experiments were performed to demonstrate the superiority of the proposed St-NLM method over the other three methods. Qualitative and quantitative results show that the proposed St-NLM method can effectively suppress the background noise, improve the contrast between vessels and background, and preserve the details of small vessels at the same time. In the human liver study, the proposed St-NLM method achieves 31.05-, 24.49-, and 11.15-dB higher contrast-to-noise ratios (CNRs) and 36.86-, 36.86-, and 15.22-dB lower noise powers than Non-NLM, PD-NLM, and S-NLM, respectively. In the human spinal cord tumor, the full-width at half-maximums (FWHMs) of vessel cross Section are 76, 201, and [Formula: see text] for St-NLM, Non-NLM, and S-NLM, respectively. The proposed St-NLM method can enhance the microvascular visualization in uPDI and has the potential for the diagnosis of many microvessel-change-related diseases.

Intensity distribution segmentation in ultrafast Doppler combined with scanning laser confocal microscopy for assessing vascular changes associated with ageing in murine hippocampi

The hippocampus plays an important role in learning and memory, requiring high-neuronal oxygenation. Understanding the relationship between blood flow and vascular structure—and how it changes with ageing—is physiologically and anatomically relevant. Ultrafast Doppler (muDoppler) and scanning laser confocal microscopy (SLCM) are powerful imaging modalities that can measure in vivo cerebral blood volume (CBV) and post mortem vascular structure, respectively. Here, we apply both imaging modalities to a cross-sectional and longitudinal study of hippocampi vasculature in wild-type mice brains. We introduce a segmentation of CBV distribution obtained from muDoppler and show that this mice-independent and mesoscopic measurement is correlated with vessel volume fraction (VVF) distribution obtained from SLCM—e.g., high CBV relates to specific vessel locations with large VVF. Moreover, we find significant changes in CBV distribution and vasculature due to ageing (5 vs. 21 month-old mice), highlighting the sensitivity of our approach. Overall, we are able to associate CBV with vascular structure—and track its longitudinal changes—at the artery-vein, venules, arteriole, and capillary levels. We believe that this combined approach can be a powerful tool for studying other acute (e.g., brain injuries), progressive (e.g., neurodegeneration) or induced pathological changes.

Ultrafast Doppler imaging and ultrasound localization microscopy reveal the complexity of vascular rearrangement in chronic spinal lesion

Acute spinal cord injury (SCI) leads to severe damage to the microvascular network. The process of spontaneous repair is accompanied by formation of new blood vessels; their functionality, however, presumably very important for functional recovery, has never been clearly established, as most studies so far used fixed tissues. Here, combining ultrafast Doppler imaging and ultrasound localization microscopy (ULM) on the same animals, we proceeded at a detailed analysis of structural and functional vascular alterations associated with the establishment of chronic SCI, both at macroscopic and microscopic scales. Using a standardized animal model of SCI, our results demonstrate striking hemodynamic alterations in several subparts of the spinal cord: a reduced blood velocity in the lesion site, and an asymmetrical hypoperfusion caudal but not rostral to the lesion. In addition, the worsening of many evaluated parameters at later time points suggests that the neoformed vascular network is not yet fully operational, and reveals ULM as an efficient in vivo readout for spinal cord vascular alterations. Finally, we show statistical correlations between the diverse biomarkers of vascular dysfunction and SCI severity. The imaging modality developed here will allow evaluating recovery of vascular function over time in pre-clinical models of SCI. Also, used on SCI patients in combination with other quantitative markers of neural tissue damage, it may help classifying lesion severity and predict possible treatment outcomes in patients.

A New Plane Wave Compounding Scheme Using Phase Compensation for Motion Detection.

Plane wave (PW) transmission has enabled multiple new applications, such as shear wave elastography, ultrafast Doppler imaging, and functional ultrasound imaging. PW compounding (PWC), which coherently sums the echo signals from multiple PW transmits with different angles, is widely used to improve B-mode image quality. When the motion between two speckle images is estimated, PWC suffers from an inherent displacement estimation error. This is derived theoretically and experimentally demonstrated in this work. We show that the phase difference between the acquired data with PW emissions with different angles is related to this error. When the absolute value of the phase difference is larger than π /2, the displacement estimation error occurs. A new scheme, named initial-phase-compensated PWC (IPCPWC), is proposed, which compensates the phase of echo signals from each PW transmit and maintains the absolute value of the phase difference smaller than π /2. The increased signal-to-noise ratio and reduced jitter of IPCPWC in motion data are demonstrated using tissue mimicking phantoms compared with PWC.

Ultrafast ultrasound localization microscopy method for spinal cord mircovasculature imaging

Function of spinal cord is crucial to nerve conduction pathway. Traumatic spinal cord injury often results in a vasculature disruption after primary insult and further leads to abnormal responses of the intact vessels in neighboring tissue during secondary injury. Therefore, the vasculature and blood supply play significant roles in evaluating the spinal cord function . Ultrasound localization microscopy (ULM) overcomes the shortcomings of extensively used angiography, such as computed tomography angiography (CTA) and magnetic resonance angiography (MRA), in terms of limited resolution, radiation and poor-portability, which meets the needs of comprehensive intraoperative examination and prognosis tracking. In this study, an L22-14vX probe with a transmission frequency of 15.625 MHz is utilized, yielding an imaging wavelength of 100 μm. The ULM is conducted based on ultrafast ultrasound technology with multiple tilted plane-wave illuminations. Robust principal component analysis (RPCA) based spatial-temporal clutter filtering method is used for separating the microbubble signals from tissue signals and high frequency noise. Through microbubble localization, trajectory tracking and mapping, subwavelength super-resolution ultrasound imaging is finally achieved. The whole process of microbubble localization and vessel reconstruction are monitored through measuring the time dependent microbubble detections and saturation. Saturation curve corresponds to the time dependent total area covered by microbubble detections on the image. Quantification analysis is carried out for evaluating the imaging results including resolution measurements based on the Fourier ring correlation (FRC) and full-width at half-maximum (FWHM). The <i>i</i><i>n-vivo</i> experimental results show that ULM can be used to obtain super-resolution vasculature imaging in rat spinal cord. The velocity distributed from 1 mm/s to 50 mm/s can be detected. Within the same vessel, the velocity of a point is inversely correlated with the distance from the point to the center of the vessel. The velocity in the center of the vessel is larger than that at the wall of the vessel. The larger vessels support higher flow in the center of the vessel. The FWHM results indicate that ultrafast Doppler displays vessels in diameters between 135 μm and 270 μm while ULM displays them in diameters between 28 μm and 35 μm. The FRC-based resolution evaluation shows that the ULM achieves a super resolution of 16 μm, much less than the imaging wavelength of 100 μm. Yet, long acquisition time is required to detect microbubbles in the smallest vessels, leading to long reconstruction of the microvasculature, which is still a problem worth studying . Compromise between saturation and acquisition time needs considering. Generally speaking, microbubbles are more likely to flow in large vessels, leading to relatively short reconstruction time of large vessels. When saturation curve almost converges, the imaging improvement with new vessels is not so significant that the detail sacrifice of some small microvessels can reduce acquisition time (i.e. most of microvasculature can still be gained when the saturation curve does not converge). Besides, the increase of microbubble concentration and advanced track identification and extraction may also accelerate the saturation rate of convergence with acquisition time decreasing. In conclusion, ULM can be used to obtain a super-resolution imaging of spinal cord microvasculature, giving a 10-fold improvement in resolution in comparison with ultrafast Doppler imaging. Relevant results can facilitate the super-resolution ULM imaging of spinal cord which may promote the function diagnosis, treatment intervention, disability prevention, and prognosis recovery of spinal cord injury.

Study on the Application of Super-Resolution Ultrasound for Cerebral Vessel Imaging in Rhesus Monkeys.

Background: Ultrasound is ideal for displaying intracranial great vessels but not intracranial microvessels and terminal vessels. Even with contrast agents, the imaging effect is still unsatisfactory. In recent years, significant theoretical advances have been achieved in super-resolution imaging. The latest commonly used ultrafast plane-wave ultrasound Doppler imaging of the brain and microbubble-based super-resolution ultrasound imaging have been applied to the imaging of cerebral microvessels and blood flow in small animals such as mice but have not been applied to in vivo imaging of the cerebral microvessels in monkeys and larger animals. In China, preliminary research results have been obtained using super-resolution imaging in certain fields but rarely in fundamental and clinical experiments on large animals. In recent years, we have conducted a joint study with the Xi'an Jiaotong University to explore the application and performance of this new technique in the diagnosis of cerebrovascular diseases in large animals.Objective: To explore the characteristics and advantages of microbubble-based super-resolution ultrasound imaging of intracranial vessels in rhesus monkeys compared with conventional transcranial ultrasound.Methods: First, the effectiveness and feasibility of the super-resolution imaging technique were verified by modular simulation experiments. Then, the imaging parameters were adjusted based on in vitro experiments. Finally, two rhesus monkeys were used for in vivo experiments of intracranial microvessel imaging.Results: Compared with conventional plane-wave imaging, super-resolution imaging could measure the inner diameters of cerebral microvessels at a resolution of 1 mm or even 0.7 mm and extract blood flow information. In addition, it has a better signal-to-noise ratio (5.625 dB higher) and higher resolution (~30-fold higher). The results of the experiments with rhesus monkeys showed that microbubble-based super-resolution ultrasound imaging can achieve an optimal resolution at the micron level and an imaging depth >35 mm.Conclusion: Super-resolution imaging can realize the monitoring imaging of high-resolution and fast calculation of microbubbles in the process of tissue damage, providing an important experimental basis for the clinical application of non-invasive transcranial ultrasound.

Abstract 10644: Impact of Cardiopulmonary Bypass Surgery on Myocardial Perfusion Assessed by Ultrafast Power Doppler: A Human Proof-of-Concept Study

Introduction: Inadequate myocardial coronary perfusion is a major cause of cardiac dysfunction in several clinical settings including congenital heart disease and cardiopulmonary bypass surgery (CPB). Blood flow to the myocardium (i.e. coronary perfusion) is primarily controlled by the coronary microvasculature (vessels < 500 μm) which plays a key part in coronary perfusion autoregulation. Until recently, direct quantitative coronary perfusion assessment had been infeasible due to limitations in spatial and/or temporal resolution of clinical imaging modalities. The study objective is to assess if ultrafast ultrasound-mediated power Doppler (PD) can approximate changes in myocardial perfusion in humans. Methods: We used a 6.9 MHz linear array probe connected to a programmable ultrafast ultrasound scanner (Verasonics Vantage®). We included 7 neonates with transposition of the great arteries (TGA) and acquired epicardial ultrafast acquisitions immediately before and after CPB (arterial switch operation) via open chest. The acquisitions were acquired at 2000 fps (PRF=10000Hz, 5 sources). Tissue clutter was separated from coronary signals with a sliding spatiotemporal filter. PD was measured as a representative of blood volume that scales with hematocrit. Fractional moving blood volume (FMBV) was calculated to normalize the PD signal: mean PD divided by the PD of the ventricular blood pool, a region with 100% vascular amplitude. Results and Conclusions: The FMBV post-operatively increased by a factor of two compared to pre-operative assessment, a reflection of hyperemia. These values returned to baseline on repeat assessment prior to discharge. Our findings suggest that ultrafast PD is a reliable tool in approximating changes in myocardial perfusion in the operating room and beyond. Thus, ultrafast power Doppler can be utilized to quantitatively assess the impact of CPB on coronary perfusion in humans.

Abstract 9565: Quantitative Assessment of Neonatal Brain Perfusion by Ultrafast Power Doppler in the Operating Room

Introduction: The main challenge with cardiopulmonary bypass (CPB) surgery in newborns with congenital heart disease is to prevent ischemic brain injury impacting on the long-term neurodevelopmental outcomes. To date, no quantitative method is available to adapt the CBP parameters for optimal per-operative cerebral perfusion. Ultrafast power Doppler (UPD) is a new portative bedside technique to map and quantify cerebral perfusion. Our objective was to evaluate UPD for quantifying the variation of cerebral perfusion in neonates during CBP surgery. Methods: UPD was performed in 5 newborns with hypoplastic left heart syndrome undergoing a Norwood procedure and 5 age-matched healthy newborns. Using a 6.9 MHz linear array probe (11L, General Electric) connected to a programmable and portable ultrafast ultrasound scanner (Vantage 256, Verasonics Inc.), via a transfontanellar approach, six pre-defined brain imaging planes were acquired in sagittal and coronal views. Assessments were performed pre-operatively, during various perfusions states intra-operatively and 24-48 hours post-operatively. Global and regional cerebral blood volume (CBV) and resistivity index (RI) maps from UPD were obtained. Results: The baseline brain perfusion was the same for both groups (p=0.62). During CPB, whole brain and regional CBV decreases more than 50% compared to baseline and reaching approximately 25% of initial CBV during selective brain perfusion and during the final stages of bypass (Figure). RI maps shows intermittent overall decrease of vascular resistivities below 0.5 on bypass and selective brain perfusion before returning to baseline in post-op, reflecting an overall decrease of the cerebral vascular resistance during CPB. Conclusions: UPD demonstrates variation in cerebral vascular resistance and blood volume in neonates undergoing CPB surgery. UPD paves the road for optimization of CPB parameters in neonates undergoing cardiac surgery.

Carotid plaque vulnerability assessed by combined shear wave elastography and ultrafast doppler compared to histology: the UF-plaque study

Abstract Purpose New biomarkers are needed to assess the vulnerability of carotid plaque to guide carotid surgery decision. Ultrafast Ultrasound Imaging (UUI) provides an estimation of plaque stiffness by Shear Wave Elastography (SWE) and the quantification of wall shear stress (WSS) by ultrafast Doppler. We aimed at evaluating the plaque stiffness and WSS applied on the plaque as potential biomarkers of plaque vulnerability. Methods Patients were referred for carotid endarterectomy because of symptomatic or asymptomatic carotid stenosis. Their plaques were evaluated by UUI within 48 hours before surgery. For each plaque, WSS and SWE were obtained on a longitudinal view at the stenosis. After endarterectomy, gross analysis and histology were performed on each removed plaque. Results 46 plaques with SWE data and 29 with WSS data were analysed. Histological analysis revealed 29 vulnerable and 17 stable plaques. Analysis of the Gray Scale Median by B mode, mean and standard deviation of stiffness by SWE were not helpful in identifying vulnerable plaques. Figure 1 presents the SWE acquisition on one plaque (A) and the distribution of plaque's stiffness average over all plaques showing the 4 ranges of stiffness (B). SWE analysis revealed that the percentage of stiffness range of [3–5] m/s was significantly increased in vulnerable plaques (p=0.048) (Figure 2A). WSS alone showed no significant difference between stable and vulnerable plaques regardless of which segment of the plaque was analysed. A multiparametric score using maximal WSS at the peak of the plaque associated with SWE texture analysis parameters was created by a stepwise analysis, leading to a score with a sensitivity of 80% and a specificity of 78%. The ROC curve of this score found an AUC of 0.85 (Figure 2B). Conclusions Multiparameter scoring including plaque stiffness and flow analysis using ultrafast ultrasound imaging allows an effective identification of histologically vulnerable carotid plaques. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Fédération Française de cardiologieSociété Française de Cardiologie Figure 1Figure 2

A Micro-flow Phantom for Superficial Micro-vasculature Imaging

Visualization of cutaneous micro-vasculatures is a powerful approach assisting in the diagnosis of skin vascular disorders. These minute structures can be visualized by high-frequency ultrasound (HFUS) using ultrafast Doppler imaging. Ultrasound flow phantoms have been used as assessment tools to evaluate the performance of the ultrasound imaging system, however, to optimize the imaging system for visualization of micro-structures, flow phantom with micro-channels is required which are usually difficult to fabricate. Here, we design a simple approach for micro-flow phantom which is easy to fabricate and cast for detection of micro-circulation in superficial micro-structures. The proposed approach features (i) the micro-channels of 200-micron at the depth of 4 mm (ii) casted in the cryogel mixture of Poly-vinyl alcohol (PVA) and (iii) infused at flow speed of 30 mm/s using infusion pump. Visualization of micro-flow channel in power Doppler image obtained by HFUS ultrafast Doppler imaging reveals that the proposed micro-flow phantom could serve as a viable assessment tool for optimizing the system for in-vivo cutaneous micro-vasculature imaging.

Wall shear stress mapping for human femoral artery based on ultrafast ultrasound vector Doppler estimations.

Wall shear stress (WSS), a type of friction exerted on the artery wall by flowing blood, is considered a crucial factor in atherosclerotic plaque development. Currently, achieving a reliable WSS mapping of an artery noninvasively by using existing imaging modalities is still challenging. In this study, a WSS mapping based on vector Doppler flow velocity estimation was proposed to measure the dynamic WSS on the human femoral artery. Because ultrafast ultrasound imaging was used here, flow-enhanced imaging was also performed to observe the moving blood flow condition. The performance of WSS mapping was verified using both straight (8mm in diameter) and stenosis (70% of stenosis) phantoms under a pulsatile flow condition. A human study was conducted from five healthy volunteers. Experimental results demonstrated that the WSS estimation was close to the standard value that was obtained from maximum velocity estimation in straight phantom experiments. In a stenosis phantom experiment, a low WSS region was observed at a site downstream of an obstruction, which is a high-risk area for plaque formation. Dynamic WSS mapping was accomplished in measurement in the femoral artery bifurcation. In measurements, the time-averaged WSS of the common femoral artery, superficial femoral artery, and deep femoral artery was 0.52± 0.19, 0.44 ± 0.21, and 0.29 ± 0.16Pa, respectively, for the anterior wall and 0.29 ± 0.11, 0.54 ± 0.24, and 0.23 ± 0.10Pa, respectively, for the posterior wall. All results indicated that WSS mapping has the potential to be a useful tool for vessel duplex scanning in the future.

A functional ultrasound brain GPS for automatic vascular-based neuronavigation

Recent advances in ultrasound imaging triggered by transmission of ultrafast plane waves have rendered functional ultrasound (fUS) imaging a valuable neuroimaging modality capable of mapping cerebral vascular networks, but also for the indirect capture of neuronal activity with high sensitivity thanks to the neurovascular coupling. However, the expansion of fUS imaging is still limited by the difficulty to identify cerebral structures during experiments based solely on the Doppler images and the shape of the vessels. In order to tackle this challenge, this study introduces the vascular brain positioning system (BPS), a GPS of the brain. The BPS is a whole-brain neuronavigation system based on the on-the-fly automatic alignment of ultrafast ultrasensitive transcranial Power Doppler volumic images to common templates such as the Allen Mouse Brain Common Coordinates Framework. This method relies on the online registration of the complex cerebral vascular fingerprint of the studied animal to a pre-aligned reference vascular atlas, thus allowing rapid matching and identification of brain structures. We quantified the accuracy of the automatic registration using super-resolution vascular images obtained at the microscopic scale using Ultrasound Localization Microscopy and found a positioning error of 44 µm and 96 µm for intra-animal and inter-animal vascular registration, respectively. The proposed BPS approach outperforms the manual vascular landmark recognition performed by expert neuroscientists (inter-annotator errors of 215 µm and 259 µm). Using the online BPS approach coupled with the Allen Atlas, we demonstrated the capability of the system to position itself automatically over chosen anatomical structures and to obtain corresponding functional activation maps even in complex oblique planes. Finally, we show that the system can be used to acquire and estimate functional connectivity matrices automatically. The proposed functional ultrasound on-the-fly neuronavigation approach allows automatic brain navigation and could become a key asset to ensure standardized experiments and protocols for non-expert and expert researchers.

Dealiasing High-Frame-Rate Color Doppler Using Dual-Wavelength Processing.

Doppler ultrasound is the premier modality to analyze blood flow dynamics in clinical practice. With conventional systems, Doppler can either provide a time-resolved quantification of the flow dynamics in sample volumes (spectral Doppler) or an average Doppler velocity/power [color flow imaging (CFI)] in a wide field of view (FOV) but with a limited frame rate. The recent development of ultrafast parallel systems made it possible to evaluate simultaneously color, power, and spectral Doppler in a wide FOV and at high-frame rates but at the expense of signal-to-noise ratio (SNR). However, like conventional Doppler, ultrafast Doppler is subject to aliasing for large velocities and/or large depths. In a recent study, staggered multi-pulse repetition frequency (PRF) sequences were investigated to dealias color-Doppler images. In this work, we exploit the broadband nature of pulse-echo ultrasound and propose a dual-wavelength approach for CFI dealiasing with a constant PRF. We tested the dual-wavelength bandpass processing, in silico, in laminar flow phantom and validated it in vivo in human carotid arteries ( n = 25 ). The in silico results showed that the Nyquist velocity could be extended up to four times the theoretical limit. In vivo, dealiased CFI were highly consistent with unfolded Spectral Doppler ( r2=0.83 , y=1.1x+0.1 , N=25 ) and provided consistent vector flow images. Our results demonstrate that dual-wavelength processing is an efficient method for high-velocity CFI.

Carotid plaque vulnerability assessed by Shear Wave elastography and ultrafast Doppler compared to histology: The UF-plaque study

Ultrafast Ultrasound Imaging (UUI) provides an estimation of carotid plaque stiffness by shear wave elastography (SWE) and the quantification of wall shear stress (WSS) by ultrafast Doppler. We aimed to evaluate the combined criteria of plaque stiffness and WSS applied on the plaque as potential biomarkers of plaque vulnerability assessed by histology. We included patients for whom carotid endarterectomy had been decided by a multidisciplinary team. UUI was performed within 48 hours before surgery, and acquisitions were obtained on a carotid longitudinal view. After endarterectomy, gross examination and histological analysis were performed on each removed plaque. Forty-six plaques with SWE data and 29 with WSS data were analysed. Histological analysis revealed 29 vulnerable and 17 stable plaques. Gray Scale Median analysis by B mode, mean and standard deviation of stiffness by SWE did not differ between vulnerable and stable plaques. SWE analysis revealed that the percentage of stiffness range of [3–5] m/s was significantly increased in vulnerable plaques ( P = 0.048). WSS alone showed no difference between stable and vulnerable plaques regardless of the segment of the plaque which was analysed. A multiparametric score using maximal WSS at the peak of the plaque associated with SWE texture analysis parameters was calculated by stepwise regression, leading to a score with a sensitivity of 80% and a specificity of 78%. Area under the Receiver Operating Characteristics curve was 0.85. A multiparameter scoring system including plaque stiffness and flow analysis using UUI allows to effectively identify histologically vulnerable carotid plaques.

Whole-Brain 3D Activation and Functional Connectivity Mapping in Mice using Transcranial Functional Ultrasound Imaging.

Functional ultrasound (fUS) imaging is a novel brain imaging modality that relies on the high-sensitivity measure of the cerebral blood volume achieved by ultrafast doppler angiography. As brain perfusion is strongly linked to local neuronal activity, this technique allows the whole-brain 3D mapping of task-induced regional activation as well as resting-state functional connectivity, non-invasively, with unmatched spatio-temporal resolution and operational simplicity. In comparison with fMRI (functional magnetic resonance imaging), a main advantage of fUS imaging consists in enabling a complete compatibility with awake and behaving animal experiments. Moreover, fMRI brain mapping in mice, the most used preclinical model in Neuroscience, remains technically challenging due to the small size of the brain and the difficulty to maintain stable physiological conditions. Here we present a simple, reliable and robust protocol for whole-brain fUS imaging in anesthetized and awake mice using an off-the-shelf commercial fUS system with a motorized linear transducer, yielding significant cortical activation following sensory stimulation as well as reproducible 3D functional connectivity pattern for network identification.

Whole-Brain 3D Activation and Functional Connectivity Mapping in Mice using Transcranial Functional Ultrasound Imaging

Functional ultrasound (fUS) imaging is a novel brain imaging modality that relies on the high-sensitivity measure of the cerebral blood volume achieved by ultrafast doppler angiography. As brain perfusion is strongly linked to local neuronal activity, this technique allows the whole-brain 3D mapping of task-induced regional activation as well as resting-state functional connectivity, non-invasively, with unmatched spatio-temporal resolution and operational simplicity. In comparison with fMRI (functional magnetic resonance imaging), a main advantage of fUS imaging consists in enabling a complete compatibility with awake and behaving animal experiments. Moreover, fMRI brain mapping in mice, the most used preclinical model in Neuroscience, remains technically challenging due to the small size of the brain and the difficulty to maintain stable physiological conditions. Here we present a simple, reliable and robust protocol for whole-brain fUS imaging in anesthetized and awake mice using an off-the-shelf commercial fUS system with a motorized linear transducer, yielding significant cortical activation following sensory stimulation as well as reproducible 3D functional connectivity pattern for network identification.

3D ultrasound coronarography: first proof of concept study on isolated beating rat hearts

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Bettencourt Foundation Background/Introduction We demonstrated recently that Ultrafast ultrasound Doppler imaging can image the intramyocardial coronary circulation in beating hearts of large animals and patients [1]. Yet, ultrasound spatial resolution remains limited by wave physics and coronaries smaller than ∼100 µm could not be imaged. Ultrasound Localization Microscopy (ULM) [2] was recently introduced to tackle this issue and exploit the micrometric localization of microbubble contrast agents at ultrafast frame rate in order to image blood flows in micrometer vessels. Purpose The objective of this work was to demonstrate that 3D ultrafast ultrasound with contrast agents can provide the full 3D mapping of the coronary microcirculation with quantitative flow velocity on a beating rat heart. Methods Acquisitions were performed on ex vivo rat hearts (n = 5) with retrograde perfusion (Langendorff model). A flow of a Krebs–Henseleit solution mixed with a diluted microbubbles solution (0.22%) was perfused at controlled pressure into the coronary arteries (between 5 and 15 mL/min). We used a 32 × 32 elements, 8-MHz matrix-array ultrasound transducer connected to a 1024-channel programmable ultrasound scanner. An ultrafast Doppler imaging sequence consisting of 9 plane waves was transmitted at a PRF of 20 kHz during 270 ms and repeated 40 times. After beamforming and SVD clutter filtering, the microbubbles were localized and tracked in 3D. Flow velocity were mapped at baseline and after infusion of Adenosine (10e-5 µMol) at constant coronary perfusion pressure (120 mm Hg). Eventually, the hearts were fixed using formaldehyde perfusion and imaged by µCT after injection of radio opaque agent. Results We successfully imaged the coronary blood flows of entire rat hearts. It revealed the entire vasculature from large main coronaries arteries (cross section up to 1 mm) to small arterioles (smaller than 40 µm). Coronary flow velocities ranged from [1 – 50] cm/s depending on the arteries diameter. Velocity estimates were validated in vitro in tubes of Ø0.58mm and were in good agreement with theoretical values of a Poiseuille’s flow (relative ratio of 10% for maximum velocities). After Adenosine infusion, perfusion flow rates increased 102% ± 50% (p < 0.05) on average. Eventually, anatomy revealed by 3D ultrasound coronarography was in accordance with the anatomy revealed by the µCT. Conclusion(s) We demonstrated the feasibility of 3D ultrasound coronarography on isolated beating rat hearts. This technique has the potential to become a novel imaging tool to investigate the coronary micro-circulation and quantify non-invasively the Coronary Flow Reserve (CFR). Abstract Figure. Ultrasound coronarography

Non-contrast-enhanced ultrafast ultrasound Doppler imaging of spinal cord micro-vessels

With the advantages of non-radiation and low-cost, ultrasound imaging has been widely used in clinical diagnosis. However, due to the compromise between temporal and spatial resolution, the traditional ultrasound imaging method which collects images line by line fails to obtain the images at a high frame rate. Ultrafast ultrasound imaging method based on the plane-wave emission can achieve a high frame rate with the capability for instantaneous hemodynamic imaging of neurovascular response. Besides, by the coherent compounding of the echo signals received from emitting a set of tilting plane-waves, the image quality can be improved in terms of resolution, contrast and signal-to-noise ratio (SNR). Considering the fact that received signals are the mixture of echo signals from the low-speed soft tissue and high-speed blood flow, a clutter filtering method is used to remove the signals of soft tissue. In this study, the ultrafast ultrasound sequence of emission and reception is designed to image the spinal cord by using the groups of multiple steering-angle plane-waves. The so-called f-k migration algorithm based on an exploding reflector model (ERM) is used for coherent plane-wave compounding. Eigenvalue decomposition (EVD) is then applied to tissue and blood signal extraction. The static tissue signals correspond to eigenvectors with low Doppler frequency shift and large magnitude eigenvalue while the high-speed blood flow signals correspond to eigenvectors with high Doppler frequency shift and small eigenvalue. Therefore, frequency and amplitude thresholds can be applied to the accurate separation of the blood component and the tissue component. After the signal extraction, the hemodynamic imaging of blood vessels can thus be obtained from the power Doppler results. The experiments are carried out by using a programmable ultrasonic array system and a high-frequency linear array transducer L22-14vX with a central frequency of 15.625 MHz. The sample acquisition frequency is set to be 62.5 MHz. In rat experiments <i>in vivo</i>, 14040 angle-stilting images per second are compounded into 520 images, each of which is compounded from 27 tilting images (the tilting angles ranging from –10° to 10°). The experiments are conducted on the anesthetized rats with part of the vertebral plate removed. The ultrafast B-mode images are acquired from a 14.0 mm ×12.7 mm region-of-interest. The 520 frames acquired in one second are processed by the clutter filter based on eigenvalue decomposition and Doppler shift analysis. The eigenvectors and eigenvalues corresponding to the soft tissue are discarded. The power Doppler images of the spinal cord micro-vessels are obtained. The experimental results indicate that the ultrafast ultrasound Doppler imaging method is effective for monitoring the hemodynamic variation in spinal cord. The micro-hemorrhage can be identified from the power Doppler images. The quantitative results indicate that the SNR increases with the steering angles increasing. Compared with the results obtained by using 9 steering angles, 5 dB SNR enhancement can be obtained by using the 27 steering angles. In conclusion, the ultrafast ultrasound Doppler technology has the potential applications in spinal cord microvascular imaging and hemodynamic evaluation of neurovascular function of spinal cord.