Ultrasound localization microscopy to image and assess microvasculature in a rat kidney.

The recent development of ultrasound localization microscopy, where individual microbubbles (contrast agents) are detected and tracked within the vasculature, provides new opportunities for imaging the vasculature of entire organs with a spatial resolution below the diffraction limit. In stationary tissue, recent studies have demonstrated a theoretical resolution on the order of microns. In this work, single microbubbles were localized in vivo in a rat kidney using a dedicated high frame rate imaging sequence. Organ motion was tracked by assuming rigid motion (translation and rotation) and appropriate correction was applied. In contrast to previous work, coherence-based non-linear phase inversion processing was used to reject tissue echoes while maintaining echoes from very slowly moving microbubbles. Blood velocity in the small vessels was estimated by tracking microbubbles, demonstrating the potential of this technique to improve vascular characterization. Previous optical studies of microbubbles in vessels of approximately 20 microns have shown that expansion is constrained, suggesting that microbubble echoes would be difficult to detect in such regions. We therefore utilized the echoes from individual MBs as microscopic sensors of slow flow associated with such vessels and demonstrate that highly correlated, wideband echoes are detected from individual microbubbles in vessels with flow rates below 2 mm/s

Ultrafast 3-D Super Resolution Ultrasound using Row-Column Array specific Coherence-based Beamforming and Rolling Acoustic Sub-aperture Processing: In Vitro, In Vivo and Clinical Study

The row-column addressed array is an emerging probe for ultrafast 3-D ultrasound imaging. It achieves this with far fewer independent electronic channels and a wider field of view than traditional 2-D matrix arrays, of the same channel count, making it a good candidate for clinical translation. However, the image quality of row-column arrays is generally poor, particularly when investigating tissue. Ultrasound localisation microscopy allows for the production of super-resolution images even when the initial image resolution is not high. Unfortunately, the row-column probe can suffer from imaging artefacts that can degrade the quality of super-resolution images as `secondary' lobes from bright microbubbles can be mistaken as microbubble events, particularly when operated using plane wave imaging. These false events move through the image in a physiologically realistic way so can be challenging to remove via tracking, leading to the production of 'false vessels'. Here, a new type of rolling window image reconstruction procedure was developed, which integrated a row-column array-specific coherence-based beamforming technique with acoustic sub-aperture processing for the purposes of reducing `secondary' lobe artefacts, noise and increasing the effective frame rate. Using an {\it{in vitro}} cross tube, it was found that the procedure reduced the percentage of `false' locations from $\sim$26\% to $\sim$15\% compared to traditional orthogonal plane wave compounding. Additionally, it was found that the noise could be reduced by $\sim$7 dB and that the effective frame rate could be increased to over 4000 fps. Subsequently, {\it{in vivo}} ultrasound localisation microscopy was used to produce images non-invasively of a rabbit kidney and a human thyroid

Ultrafast Ultrasound Imaging

Among medical imaging modalities, such as computed tomography (CT) and magnetic resonance imaging (MRI), ultrasound imaging stands out due to its temporal resolution. Owing to the nature of medical ultrasound imaging, it has been used for not only observation of the morphology of living organs but also functional imaging, such as blood flow imaging and evaluation of the cardiac function. Ultrafast ultrasound imaging, which has recently become widely available, significantly increases the opportunities for medical functional imaging. Ultrafast ultrasound imaging typically enables imaging frame-rates of up to ten thousand frames per second (fps). Due to the extremely high temporal resolution, this enables visualization of rapid dynamic responses of biological tissues, which cannot be observed and analyzed by conventional ultrasound imaging. This Special Issue includes various studies of improvements to the performance of ultrafast ultrasoun

Coherent Multi-Transducer Ultrasound Imaging

An extended aperture has the potential to greatly improve ultrasound imaging performance. This work extends the effective aperture size by coherently compounding the received radio frequency data from multiple transducers. A framework is developed in which an ultrasound imaging system consisting of $N$ synchronized matrix arrays, each with partly shared field of view, take turns to transmit plane waves. Only one individual transducer transmits at each time while all $N$ transducers simultaneously receive. The subwavelength localization accuracy required to combine information from multiple transducers is achieved without the use of any external tracking device. The method developed in this study is based on the study of the backscattered echoes received by the same transducer and resulting from a targeted scatterer point in the medium insonated by the multiple ultrasound probes of the system. The current transducer locations along with the speed of sound in the medium are deduced by optimizing the cross-correlation between these echoes. The method is demonstrated experimentally in 2-D using ultrasound point and anechoic lesion phantoms and a first demonstration of a free-hand experiment is also shown. Results demonstrate that the coherent multi-transducer imaging has the potential to improve ultrasound image quality, improving resolution and target detectability. Lateral resolution, contrast and contrast-to-noise ratio improved from 0.67 mm, -6.708 dB and 0.702, respectively, when using a single probe, to 0.18 mm, -7.251 dB and 0.721 in the coherent multi-transducer imaging case

3-D Coherent Multi-Transducer Ultrasound Imaging with Sparse Spiral Arrays

Coherent multi-transducer ultrasound (CoMTUS) creates an extended effective aperture through the coherent combination of multiple arrays, which results in images with enhanced resolution, extended field-of-view, and higher sensitivity. The subwavelength localization accuracy of the multiple transducers required to coherently beamform the data is achieved by using the echoes backscattered from targeted points. In this study, CoMTUS is implemented and demonstrated for the first time in 3-D imaging using a pair of 256-element 2-D sparse spiral arrays, which keep the channel-count low and limit the amount of data to be processed. The imaging performance of the method was investigated using both simulations and phantom tests. The feasibility of free-hand operation is also experimentally demonstrated. Results show that, in comparison to a single dense array system using the same total number of active elements, the proposed CoMTUS system improves spatial resolution (up to 10 times) in the direction where both arrays are aligned, contrast-to-noise-ratio (CNR, up to 30%), and generalized CNR (up to 11%). Overall, CoMTUS shows narrower main lobe and higher contrast-to-noise-ratio, which results in an increased dynamic range and better target detectability.Comment: 10 pages, 6 figure

3D Quasi-Static Ultrasound Elastography With Plane Wave In Vivo

In biological tissue, an increase in elasticity is often a marker of abnormalities. Techniques such as quasi-static ultrasound elastography have been developed to assess the strain distribution in soft tissues in two dimensions using a quasi-static compression. However, as abnormalities can exhibit very heterogeneous shapes, a three dimensional approach would be necessary to accurately measure their volume and remove operator dependency. Acquisition of volumes at high rates is also critical to performing real-time imaging with a simple freehand compression. In this study, we developed for the first time a 3D quasi-static ultrasound elastography method with plane waves that estimates axial strain distribution in vivo in entire volumes at high volume rate. Acquisitions were performed with a 2D matrix array probe of 2.5MHz frequency and 256 elements. Plane waves were emitted at a volume rate of 100 volumes/s during a continuous motorized and freehand compression. 3D B-mode volumes and 3D cumulative axial strain volumes were successfully estimated in inclusion phantoms and in ex vivo canine liver before and after a high intensity focused ultrasound ablation. We also demonstrated the in vivo feasibility of the method using freehand compression on the calf muscle of a human volunteer and were able to retrieve 3D axial strain volume at a high volume rate depicting the differences in stiffness of the two muscles which compose the calf muscle. 3D ultrasound quasi-static elastography with plane waves could become an important technique for the imaging of the elasticity in human bodies in three dimensions using simple freehand scanning

Characterization of carotid artery plaques using noninvasive vascular ultrasound elastography

L'athérosclérose est une maladie vasculaire complexe qui affecte la paroi des artères (par l'épaississement) et les lumières (par la formation de plaques). La rupture d'une plaque de l'artère carotide peut également provoquer un accident vasculaire cérébral ischémique et des complications. Bien que plusieurs modalités d'imagerie médicale soient actuellement utilisées pour évaluer la stabilité d'une plaque, elles présentent des limitations telles que l'irradiation, les propriétés invasives, une faible disponibilité clinique et un coût élevé. L'échographie est une méthode d'imagerie sûre qui permet une analyse en temps réel pour l'évaluation des tissus biologiques. Il est intéressant et prometteur d’appliquer une échographie vasculaire pour le dépistage et le diagnostic précoces des plaques d’artère carotide. Cependant, les ultrasons vasculaires actuels identifient uniquement la morphologie d'une plaque en termes de luminosité d'écho ou l’impact de cette plaque sur les caractéristiques de l’écoulement sanguin, ce qui peut ne pas être suffisant pour diagnostiquer l’importance de la plaque. La technique d’élastographie vasculaire non-intrusive (« noninvasive vascular elastography (NIVE) ») a montré le potentiel de détermination de la stabilité d'une plaque. NIVE peut déterminer le champ de déformation de la paroi vasculaire en mouvement d’une artère carotide provoqué par la pulsation cardiaque naturelle. En raison des différences de module de Young entre les différents tissus des vaisseaux, différents composants d’une plaque devraient présenter différentes déformations, caractérisant ainsi la stabilité de la plaque. Actuellement, les performances et l’efficacité numérique sous-optimales limitent l’acceptation clinique de NIVE en tant que méthode rapide et efficace pour le diagnostic précoce des plaques vulnérables. Par conséquent, il est nécessaire de développer NIVE en tant qu’outil d’imagerie non invasif, rapide et économique afin de mieux caractériser la vulnérabilité liée à la plaque. La procédure à suivre pour effectuer l’analyse NIVE consiste en des étapes de formation et de post-traitement d’images. Cette thèse vise à améliorer systématiquement la précision de ces deux aspects de NIVE afin de faciliter la prédiction de la vulnérabilité de la plaque carotidienne. Le premier effort de cette thèse a été dédié à la formation d'images (Chapitre 5). L'imagerie par oscillations transversales a été introduite dans NIVE. Les performances de l’imagerie par oscillations transversales couplées à deux estimateurs de contrainte fondés sur un modèle de déformation fine, soit l’ « affine phase-based estimator (APBE) » et le « Lagrangian speckle model estimator (LSME) », ont été évaluées. Pour toutes les études de simulation et in vitro de ce travail, le LSME sans imagerie par oscillation transversale a surperformé par rapport à l'APBE avec imagerie par oscillations transversales. Néanmoins, des estimations de contrainte principales comparables ou meilleures pourraient être obtenues avec le LSME en utilisant une imagerie par oscillations transversales dans le cas de structures tissulaires complexes et hétérogènes. Lors de l'acquisition de signaux ultrasonores pour la formation d'images, des mouvements hors du plan perpendiculaire au plan de balayage bidimensionnel (2-D) existent. Le deuxième objectif de cette thèse était d'évaluer l'influence des mouvements hors plan sur les performances du NIVE 2-D (Chapitre 6). À cette fin, nous avons conçu un dispositif expérimental in vitro permettant de simuler des mouvements hors plan de 1 mm, 2 mm et 3 mm. Les résultats in vitro ont montré plus d'artefacts d'estimation de contrainte pour le LSME avec des amplitudes croissantes de mouvements hors du plan principal de l’image. Malgré tout, nous avons néanmoins obtenu des estimations de déformations robustes avec un mouvement hors plan de 2.0 mm (coefficients de corrélation supérieurs à 0.85). Pour un jeu de données cliniques de 18 participants présentant une sténose de l'artère carotide, nous avons proposé d'utiliser deux jeux de données d'analyses sur la même plaque carotidienne, soit des images transversales et longitudinales, afin de déduire les mouvements hors plan (qui se sont avérés de 0.25 mm à 1.04 mm). Les résultats cliniques ont montré que les estimations de déformations restaient reproductibles pour toutes les amplitudes de mouvement, puisque les coefficients de corrélation inter-images étaient supérieurs à 0.70 et que les corrélations croisées normalisées entre les images radiofréquences étaient supérieures à 0.93, ce qui a permis de démontrer une plus grande confiance lors de l'analyse de jeu de données cliniques de plaques carotides à l'aide du LSME. Enfin, en ce qui concerne le post-traitement des images, les algorithmes NIVE doivent estimer les déformations des parois des vaisseaux à partir d’images reconstituées dans le but d’identifier les tissus mous et durs. Ainsi, le dernier objectif de cette thèse était de développer un algorithme d'estimation de contrainte avec une résolution de la taille d’un pixel ainsi qu'une efficacité de calcul élevée pour l'amélioration de la précision de NIVE (Chapitre 7). Nous avons proposé un estimateur de déformation de modèle fragmenté (SMSE) avec lequel le champ de déformation dense est paramétré avec des descriptions de transformées en cosinus discret, générant ainsi des composantes de déformations affines (déformations axiales et latérales et en cisaillement) sans opération mathématique de dérivées. En comparant avec le LSME, le SMSE a réduit les erreurs d'estimation lors des tests de simulations, ainsi que pour les mesures in vitro et in vivo. De plus, la faible mise en oeuvre de la méthode SMSE réduit de 4 à 25 fois le temps de traitement par rapport à la méthode LSME pour les simulations, les études in vitro et in vivo, ce qui pourrait permettre une implémentation possible de NIVE en temps réel.Atherosclerosis is a complex vascular disease that affects artery walls (by thickening) and lumens (by plaque formation). The rupture of a carotid artery plaque may also induce ischemic stroke and complications. Despite the use of several medical imaging modalities to evaluate the stability of a plaque, they present limitations such as irradiation, invasive property, low clinical availability and high cost. Ultrasound is a safe imaging method with a real time capability for assessment of biological tissues. It is clinically used for early screening and diagnosis of carotid artery plaques. However, current vascular ultrasound technologies only identify the morphology of a plaque in terms of echo brightness or the impact of the vessel narrowing on flow properties, which may not be sufficient for optimum diagnosis. Noninvasive vascular elastography (NIVE) has been shown of interest for determining the stability of a plaque. Specifically, NIVE can determine the strain field of the moving vessel wall of a carotid artery caused by the natural cardiac pulsation. Due to Young’s modulus differences among different vessel tissues, different components of a plaque can be detected as they present different strains thereby potentially helping in characterizing the plaque stability. Currently, sub-optimum performance and computational efficiency limit the clinical acceptance of NIVE as a fast and efficient method for the early diagnosis of vulnerable plaques. Therefore, there is a need to further develop NIVE as a non-invasive, fast and low computational cost imaging tool to better characterize the plaque vulnerability. The procedure to perform NIVE analysis consists in image formation and image post-processing steps. This thesis aimed to systematically improve the accuracy of these two aspects of NIVE to facilitate predicting carotid plaque vulnerability. The first effort of this thesis has been targeted on improving the image formation (Chapter 5). Transverse oscillation beamforming was introduced into NIVE. The performance of transverse oscillation imaging coupled with two model-based strain estimators, the affine phase-based estimator (APBE) and the Lagrangian speckle model estimator (LSME), were evaluated. For all simulations and in vitro studies, the LSME without transverse oscillation imaging outperformed the APBE with transverse oscillation imaging. Nonetheless, comparable or better principal strain estimates could be obtained with the LSME using transverse oscillation imaging in the case of complex and heterogeneous tissue structures. During the acquisition of ultrasound signals for image formation, out-of-plane motions which are perpendicular to the two-dimensional (2-D) scan plane are existing. The second objective of this thesis was to evaluate the influence of out-of-plane motions on the performance of 2-D NIVE (Chapter 6). For this purpose, we designed an in vitro experimental setup to simulate out-of-plane motions of 1 mm, 2 mm and 3 mm. The in vitro results showed more strain estimation artifacts for the LSME with increasing magnitudes of out-of-plane motions. Even so, robust strain estimations were nevertheless obtained with 2.0 mm out-of-plane motion (correlation coefficients higher than 0.85). For a clinical dataset of 18 participants with carotid artery stenosis, we proposed to use two datasets of scans on the same carotid plaque, one cross-sectional and the other in a longitudinal view, to deduce the out-of-plane motions (estimated to be ranging from 0.25 mm to 1.04 mm). Clinical results showed that strain estimations remained reproducible for all motion magnitudes since inter-frame correlation coefficients were higher than 0.70, and normalized cross-correlations between radiofrequency images were above 0.93, which indicated that confident motion estimations can be obtained when analyzing clinical dataset of carotid plaques using the LSME. Finally, regarding the image post-processing component of NIVE algorithms to estimate strains of vessel walls from reconstructed images with the objective of identifying soft and hard tissues, we developed a strain estimation method with a pixel-wise resolution as well as a high computation efficiency for improving NIVE (Chapter 7). We proposed a sparse model strain estimator (SMSE) for which the dense strain field is parameterized with Discrete Cosine Transform descriptions, thereby deriving affine strain components (axial and lateral strains and shears) without mathematical derivative operations. Compared with the LSME, the SMSE reduced estimation errors in simulations, in vitro and in vivo tests. Moreover, the sparse implementation of the SMSE reduced the processing time by a factor of 4 to 25 compared with the LSME based on simulations, in vitro and in vivo results, which is suggesting a possible implementation of NIVE in real time

Biomolecular Ultrasound and Sonogenetics

Visualizing and modulating molecular and cellular processes occurring deep within living organisms is fundamental to our study of basic biology and disease. Currently, the most sophisticated tools available to dynamically monitor and control cellular events rely on light-responsive proteins, which are difficult to use outside of optically transparent model systems, cultured cells, or surgically accessed regions owing to strong scattering of light by biological tissue. In contrast, ultrasound is a widely used medical imaging and therapeutic modality that enables the observation and perturbation of internal anatomy and physiology but has historically had limited ability to monitor and control specific cellular processes. Recent advances are beginning to address this limitation through the development of biomolecular tools that allow ultrasound to connect directly to cellular functions such as gene expression. Driven by the discovery and engineering of new contrast agents, reporter genes, and bioswitches, the nascent field of biomolecular ultrasound carries a wave of exciting opportunities

Simultaneous transmission and reception on all elements of an array: binary code excitation

Pulse-echo arrays are used in radar, sonar, seismic, medical and non-destructive evaluation. There is a trend to produce arrays with an ever-increasing number of elements. This trend presents two major challenges: (i) often the size of the elements is reduced resulting in a lower signal-to-noise ratio (SNR) and (ii) the time required to record all of the signals that correspond to every transmit–receive path increases. Coded sequences with good autocorrelation properties can increase the SNR while orthogonal sets can be used to simultaneously acquire all of the signals that correspond to every transmit–receive path. However, a central problem of conventional coded sequences is that they cannot achieve good autocorrelation and orthogonality properties simultaneously due to their length being limited by the location of the closest reflectors. In this paper, a solution to this problem is presented by using coded sequences that have receive intervals. The proposed approach can be more than one order of magnitude faster than conventional methods. In addition, binary excitation and quantization can be employed, which reduces the data throughput by roughly an order of magnitude and allows for higher sampling rates. While this concept is generally applicable to any field, a 16-element system was built to experimentally demonstrate this principle for the first time using a conventional medical ultrasound probe