Ultrasound Localization Microscopy (ULM) is a non-invasive technique that allows for the imaging of micro-vessels in vivo, at depth and with a resolution on the order of ten microns. ULM is based on the sub-resolution localization of individual microbubbles injected in the bloodstream. Mapping the whole angioarchitecture requires the accumulation of microbubbles trajectories from thousands of frames, typically acquired over a few minutes. ULM acquisition times can be reduced by increasing the microbubble concentration, but requires more advanced algorithms to detect them individually. Several deep learning approaches have been proposed for this task, but they remain limited to 2D imaging, in part due to the associated large memory requirements. Herein, we propose the use of sparse tensor neural networks to enable deep learning-based 3D ULM by improving memory scalability with increased dimensionality. We study several approaches to efficiently convert ultrasound data into a sparse format and study the impact of the associated loss of information. When applied in 2D, the sparse formulation reduces the memory requirements by a factor 2 at the cost of a small reduction of performance when compared against dense networks. In 3D, the proposed approach reduces memory requirements by two order of magnitude while largely outperforming conventional ULM in high concentration settings. We show that Sparse Tensor Neural Networks in 3D ULM allow for the same benefits as dense deep learning based method in 2D ULM i.e. the use of higher concentration in silico and reduced acquisition time.

Ultrasound Localization Microscopy (ULM) has proven effective in resolving microvascular structures and local mean velocities at sub-diffraction-limited scales, offering high-resolution imaging capabilities. Dynamic ULM (DULM) enables the creation of angiography or velocity movies throughout cardiac cycles. Currently, these techniques rely on a Localization-and-Tracking (LAT) workflow consisting in detecting microbubbles (MB) in the frames before pairing them to generate tracks. While conventional LAT methods perform well at low concentrations, they suffer from longer acquisition times and degraded localization and tracking accuracy at higher concentrations, leading to biased angiogram reconstruction and velocity estimation. In this study, we propose a novel approach to address these challenges by reversing the current workflow. The proposed method, Tracking-and-Localization (TAL), relies on first tracking the MB and then performing localization. Through comprehensive benchmarking using both in silico and in vivo experiments and employing various metrics to quantify ULM angiography and velocity maps, we demonstrate that the TAL method consistently outperforms the reference LAT workflow. Moreover, when applied to DULM, TAL successfully extracts velocity variations along the cardiac cycle with improved repeatability. The findings of this work highlight the effectiveness of the TAL approach in overcoming the limitations of conventional LAT methods, providing enhanced ULM angiography and velocity imaging.

3D Imaging of the human heart at high frame rate is of major interest for various clinical applications. Electronic complexity and cost has prevented the dissemination of 3D ultrafast imaging into the clinic. Row column addressed (RCA) transducers provide volumetric imaging at ultrafast frame rate by using a low electronic channel count, but current models are ill-suited for transthoracic cardiac imaging due to field-of-view limitations. In this study, we proposed a mechanically curved RCA with an aperture adapted for transthoracic cardiac imaging ( 24×16 mm2). The RCA has a toroidal curved surface of 96 elements along columns (curvature radius rC = 4.47 cm) and 64 elements along rows (curvature radius rR = 3 cm). We implemented delay and sum beamforming with an analytical calculation of the propagation of a toroidal wave which was validated using simulations (Field II). The imaging performance was evaluated on a calibrated phantom. Experimental 3D imaging was achieved up to 12 cm deep with a total angular aperture of 30° for both lateral dimensions. The Contrast-to-Noise ratio increased by 12 dB from 2 to 128 virtual sources. Then, 3D Ultrasound Localization Microscopy (ULM) was characterized in a sub-wavelength tube diameter. Finally, 3D ULM was demonstrated on a perfused ex-vivo swine heart to image the coronary microcirculation.

Ultrasound Localization Microscopy (ULM) can map microvessels at a resolution of a few micrometers ( [Formula: see text]). Transcranial ULM remains challenging in presence of aberrations caused by the skull, which lead to localization errors. Herein, we propose a deep learning approach based on recently introduced complex-valued convolutional neural networks (CV-CNNs) to retrieve the aberration function, which can then be used to form enhanced images using standard delay-and-sum beamforming. CV-CNNs were selected as they can apply time delays through multiplication with in-phase quadrature input data. Predicting the aberration function rather than corrected images also confers enhanced explainability to the network. In addition, 3D spatiotemporal convolutions were used for the network to leverage entire microbubble tracks. For training and validation, we used an anatomically and hemodynamically realistic mouse brain microvascular network model to simulate the flow of microbubbles in presence of aberration. The proposed CV-CNN performance was compared to the coherence-based method by using microbubble tracks. We then confirmed the capability of the proposed network to generalize to transcranial in vivo data in the mouse brain (n=3). Vascular reconstructions using a locally predicted aberration function included additional and sharper vessels. The CV-CNN was more robust than the coherence-based method and could perform aberration correction in a 6-month-old mouse. After correction, we measured a resolution of [Formula: see text] for younger mice, representing an improvement of 25.8%, while the resolution was improved by 13.9% for the 6-month-old mouse. This work leads to different applications for complex-valued convolutions in biomedical imaging and strategies to perform transcranial ULM.

An increased pulse pressure, due to arteries stiffening with age and cardiovascular disease, may lead to downstream brain damage in microvessels and cognitive decline. Brain-wide imaging of the pulsatility propagation from main feeding arteries to capillaries in small animals could improve our understanding of the link between pulsatility and cognitive decline. However, it requires higher spatiotemporal resolution and penetration depth than currently available with existing brain imaging techniques. Herein, we show the feasibility of performing Dynamic Ultrasound Localization Microscopy (DULM), a novel imaging approach to capture hemodynamics with a subwavelength resolution. By producing cine-loops of flowing microbubbles in 2D in the whole rodent brain lasting several cardiac cycles, DULM performed pulsatility measurements in microvessels in-depth, in vivo, with and without craniotomy. Cortical veins and arteries were shown to have a significatively different pulsatility index and the method was compared against Contrast Enhanced Ultrafast Ultrasound Doppler (CEUFD) pulsatility measurements.

Dynamic Myocardial Ultrasound Localization Angiography (MULA) is an ultrasound-based imaging modality destined to enhance the diagnosis and treatment monitoring of coronary pathologies. Current diagnosis methods of coronary artery disease focus on the observation of vessel narrowing in the coronary vasculature to assess the organ's condition. However, we would strongly benefit from mapping and measuring flow from intramyocardial arterioles and capillaries as they are the direct vehicle of the myocardium blood income. With the advent of ultrafast ultrasound scanners, imaging modalities based on the localization and tracking of injected microbubbles allow for the subwavelength resolution imaging of an organ's vasculature. Yet, the application of these vascular imaging modalities relies on an accumulation of cine loops of a region of interest undergoing no or minimal tissue motion. This work introduces the MULA framework that combines 1) the mapping of the dynamics of the microvascular flow using an ultrasound sequence triggered by the electrocardiogram with a 2) novel Lagrangian beamformer based on non-rigid motion registration algorithm to form images directly in the myocardium's material coordinates and thus correcting for the large myocardial motion and deformation. Specifically, we show that this framework enables the non-invasive imaging of the angioarchitecture and dynamics of intramyocardial flow in vessels as small as a few tens of microns in the rat's beating heart in vivo.

Ultrasound Localization Microscopy (ULM) can resolve the microvascular bed down to a few micrometers. To achieve such performance, microbubble contrast agents must perfuse the entire microvascular network. Microbubbles are then located individually and tracked over time to sample individual vessels, typically over hundreds of thousands of images. To overcome the fundamental limit of diffraction and achieve a dense reconstruction of the network, low microbubble concentrations must be used, which leads to acquisitions lasting several minutes. Conventional processing pipelines are currently unable to deal with interference from multiple nearby microbubbles, further reducing achievable concentrations. This work overcomes this problem by proposing a Deep Learning approach to recover dense vascular networks from ultrasound acquisitions with high microbubble concentrations. A realistic mouse brain microvascular network, segmented from 2-photon microscopy, was used to train a three-dimensional convolutional neural network (CNN) based on a V-net architecture. Ultrasound data sets from multiple microbubbles flowing through the microvascular network were simulated and used as ground truth to train the 3D CNN to track microbubbles. The 3D-CNN approach was validated in silico using a subset of the data and in vivo in a rat brain. In silico, the CNN reconstructed vascular networks with higher precision (81%) than a conventional ULM framework (70%). In vivo, the CNN could resolve micro vessels as small as 10 μ m with an improvement in resolution when compared against a conventional approach.

Ultrasound vascular strain imaging has shown its potential to interrogate the motion of the vessel wall induced by the cardiac pulsation for predicting plaque instability. In this study, a sparse model strain estimator (SMSE) is proposed to reconstruct a dense strain field at a high resolution, with no spatial derivatives, and a high computation efficiency. This sparse model utilizes the highly-compacted property of discrete cosine transform (DCT) coefficients, thereby allowing to parameterize displacement and strain fields with truncated DCT coefficients. The derivation of affine strain components (axial and lateral strains and shears) was reformulated into solving truncated DCT coefficients and then reconstructed with them. Moreover, an analytical solution was derived to reduce estimation time. With simulations, the SMSE reduced estimation errors by up to 50% compared with the state-of-the-art window-based Lagrangian speckle model estimator (LSME). The SMSE was also proven to be more robust than the LSME against global and local noise. For in vitro and in vivo tests, residual strains assessing cumulated errors with the SMSE were 2 to 3 times lower than with the LSME. Regarding computation efficiency, the processing time of the SMSE was reduced by 4 to 25 times compared with the LSME, according to simulations, in vitro and in vivo results. Finally, phantom studies demonstrated the enhanced spatial resolution of the proposed SMSE algorithm against LSME.

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 N2elements 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.

A coupled computational method for recovering tissue velocity vector fields from high-frame-rate echocardiography is described. Conventional transthoracic echocardiography provides limited temporal resolution, which may prevent accurate estimation of the 2-D myocardial velocity field dynamics. High-frame-rate compound echocardiography using diverging waves with integrated motion compensation has been shown to provide concurrent high-resolution B-mode and tissue Doppler imaging (TDI). In this paper, we propose a regularized least-squares method to provide accurate myocardial velocities at high frame rates. The velocity vector field was formulated as the minimizer of a cost function that is a weighted sum of: 1) the ${\ell }^{{2}}$ -norm of the material derivative of the B-mode images (optical flow); 2) the ${\ell }^{{2}}$ -norm of the tissue-Doppler residuals; and 3) a quadratic regularizer that imposes spatial smoothness and well-posedness. A finite difference discretization of the continuous problem was adopted, leading to a sparse linear system. The proposed framework was validated in vitro on a rotating disk with speeds up to 20 cm/s, and compared with speckle tracking echocardiography (STE) by block matching. It was also validated in vivo against TDI and STE in a cross-validation strategy involving parasternal long axis and apical three-chamber views. The proposed method based on the combination of optical flow and tissue Doppler led to more accurate time-resolved velocity vector fields.

Color Doppler imaging is an established pulsed ultrasound technique to visualize blood flow non-invasively. High-frame-rate (ultrafast) color Doppler, by emissions of plane or circular wavefronts, allows severalfold increase in frame rates. Conventional and ultrafast color Doppler are both limited by the range-velocity dilemma, which may result in velocity folding (aliasing) for large depths and/or large velocities. We investigated multiple pulse-repetition-frequency (PRF) emissions arranged in a series of staggered intervals to remove aliasing in ultrafast color Doppler. Staggered PRF is an emission process where time delays between successive pulse transmissions change in an alternating way. We tested staggered dual- and triple-PRF ultrafast color Doppler, 1) in vitro in a spinning disc and a free jet flow, and 2) in vivo in a human left ventricle. The in vitro results showed that the Nyquist velocity could be extended to up to 6 times the conventional limit. We found coefficients of determination r(2) ≥ 0.98 between the de-aliased and ground-truth velocities. Consistent de-aliased Doppler images were also obtained in the human left heart. Our results demonstrate that staggered multiple-PRF ultrafast color Doppler is efficient for high-velocity high-frame-rate blood flow imaging. This is particularly relevant for new developments in ultrasound imaging relying on accurate velocity measurements.

Plane strain tensor estimation using non-invasive vascular ultrasound elastography (NIVE) can be difficult to achieve using conventional focus beamforming due to limited lateral resolution and frame rate. Recent developments in compound plane wave (CPW) imaging have led to high speed and high resolution imaging. In this study, we present the performance of NIVE using coherent CPW. We show the impact of CPW beamforming on strain estimates compared to conventional focus sequences. To overcome the inherent variability of lateral strains, associated with the low lateral resolution of linear array transducers, we use the plane strain incompressibility to constrain the estimator. Taking advantage of the approximate tenfold increase in frame rate of CPW compared with conventional focus imaging, we introduce a time-ensemble estimation approach to further improve the elastogram quality. By combining CPW imaging with the constrained Lagrangian speckle model estimator, we observe an increase in elastography quality (∼ 10 dB both in signal-to-noise and contrast-to-noise ratios) over a wide range of applied strains (0.02 to 3.2%).

The homodyned K-distribution appears naturally in the context of random walks and provides a useful model for the distribution of the received intensity in a wide range of non-Gaussian scattering configurations, including medical ultrasonics. An estimation method for the homodyned K-distribution based on the first moment of the intensity and two log-moments (XU method), namely the $X$- and $U$-statistics previously studied in the special case of the K-distribution, is proposed as an alternative to a method based on the first three moments of the intensity (MI method) or the amplitude (MA method), and a method based on the signal-to-noise ratio (SNR), the skewness, and the kurtosis of two fractional orders of the amplitude (labeled RSK method). Properties of the $X$- and $U$-statistics for the homodyned K-distribution are proved, except for one conjecture. Using these properties, an algorithm based on the bisection method for monotonous functions was developed. The algorithm has a geometric rate of convergence. Various tests were performed to study the behavior of the estimators. It was shown with simulated data samples that the estimations of the parameters $1/\alpha$ and $1/(\kappa+1)$ of the homodyned K-distribution are preferable to the direct estimations of the clustering parameter $\alpha$ and the structure parameter $\kappa$ (with respective relative root mean squared errors (RMSEs) of $0.63$ and $0.13$, as opposed to $1.04$ and $4.37$, when $N=1000$). Tests on simulated ultrasound images with only diffuse scatterers (up to $10$ per resolution cell) indicated that the XU estimator is overall more reliable than the other three estimators for the estimation of $1/\alpha$, with relative RMSEs of 0.79 (MI), 0.61 (MA), 0.53 (XU), and 0.67 (RSK). For the parameter $1/(\kappa+1)$, the relative RMSEs were equal to 0.074 (MI), 0.075 (MA), 0.069 (XU), and 0.100 (RSK). In the case of a large number of scatterers (11 to 20 per resolution cell), the relative RMSEs of $1/\alpha$ were equal to 1.43 (MI), 1.27 (MA), 1.25 (XU), and 1.33 (RSK), and the relative RMSEs of $1/(\kappa+1)$ were equal to 0.14 (MI), 0.16 (MA), 0.17 (XU), and 0.20 (RSK). The four methods were also tested on simulated ultrasound images with a variable density of periodic scatterers to test images with a coherent component. The addition of noise on ultrasound images was also studied. Results showed that the XU estimator was better overall than the other three. Finally, on the simulated ultrasound images, the average computation times per image were equal to 6.0 ms (MI), 8.0 ms (MA), 6.8 ms (XU), and 500 ms (RSK). Thus, a fast, reliable, and novel algorithm for the estimation of the homodyned K-distribution was proposed.