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

Atherosclerotic Plaque Characterization in Humans with Acoustic Radiation Force Impulse (ARFI) Imaging

Cardio- and cerebrovascular diseases (CVD) are among the leading causes of death and disability in the United States. A vast majority of heart attacks and strokes are linked to atherosclerosis; a condition characterized by inflammation and plaque accumulation in the arterial wall that can rupture and propagate an acute thrombotic event. Identification of plaques that are vulnerable to rupture is paramount to the prevention of heart attacks and strokes, but a noninvasive plaque characterization imaging technology that is cost-effective, safe, and accurate has remained elusive. The goal of this dissertation is to evaluate whether acoustic radiation force impulse (ARFI) imaging, an ultrasound-based elastography technique, can noninvasively characterize plaque components and identify features that have been shown to correlate with plaque vulnerability. Data are presented from preclinical studies, done in a porcine model of atherosclerosis, and clinical studies, performed in patients undergoing carotid endarterectomy (CEA), to demonstrate the sensitivity and specificity of ARFI for various plaque components. Additionally, the ability of ARFI to measure fibrous cap thickness is assessed with finite element method (FEM) modelling, and the limits of ARFI fibrous cap resolution are analyzed. Lastly, advanced ARFI-based plaque imaging methods are explored, including intravascular ARFI for coronary plaque characterization. Overall, these studies demonstrate that ARFI can delineate features consistent with vulnerable plaque in a clinical imaging context and suggest that ARFI has the potential to improve the current state of the art in atherosclerosis diagnostics.Doctor of Philosoph

Non-invasive ultrasound monitoring of regional carotid wall structure and deformation in atherosclerosis

Thesis (Ph. D.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, 2001.Includes bibliographical references (p. 223-242).Atherosclerosis is characterized by local remodeling of arterial structure and distensibility. Developing lesions either progress gradually to compromise tissue perfusion or rupture suddenly to cause catastrophic myocardial infarction or stroke. Reliable measurement of changes in arterial structure and composition is required for assessment of disease progression. Non-invasive carotid ultrasound can image the heterogeneity of wall structure and distensibility caused by atherosclerosis. However, this capability has not been utilized for clinical monitoring because of speckle noise and other artifacts. Clinical measures focus instead on average wall thickness and diameter distension in the distal common carotid to reduce sensitivity to noise. The goal of our research was to develop an effective system for reliable regional structure and deformation measurements since these are more sensitive indicators of disease progression. We constructed a system for freehand ultrasound scanning based on custom software which simultaneously acquires real-time image sequences and 3D frame localization data from an electromagnetic spatial localizer. With finite element modeling, we evaluated candidate measures of regional wall deformation.(cont.) Finally, we developed a multi-step scheme for robust estimation of local wall structure and deformation. This new strategy is based on a directionally-sensitive segmentation functional and a motion-region-of-interest constrained optical flow algorithm. We validated this estimator with simulated images and clinical ultrasound data. The results show structure estimates that are accurate and precise, with inter- and intra-observer reproducibility surpassing existing methods. Estimates of wall velocity and deformation likewise show good overall accuracy and precision. We present results from a proof-of-principle evaluation conducted in a pilot study of normal subjects and clinical patients. For one example, we demonstrate the combination of 2D image processing with 3D frame localization for visualization of the carotid volume. With slice localization, estimates of carotid wall structure and deformation can be derived for all axial positions along the carotid artery. The elements developed here provide the tools necessary for reliable quantification of regional wall structure and composition changes which result from atherosclerosis.by Raymond C. Chan.Ph.D

The determinants of intra-plaque neovascularisation: a study by contrast-enhanced carotid ultrasonography

Atherosclerosis is a chronic inflammatory disorder, initiated by arterial wall injury, mediated by well-recognised cardiovascular risk factors and culminating in formation of plaques, the patho-biological substrate that precedes events such as stroke and myocardial infarction. Intraplaque neovascularisation (IPN) is one of several defence mechanisms in response to atherosclerosis. With development of an atherosclerotic plaque within the intima, the distance between the deeper intimal layers and the luminal surface increases, producing hypoxia within the arterial wall. This stimulates release of pro-angiogenic factors that induces neoangiogenesis in an attempt to normalise oxygen tension. However, these neo-vessels are fragile, immature and leaky and thought to be the primary cause of intraplaque haemorrhage, now appreciated to be a key risk factor for plaque rupture. Therefore, the presence of IPN is now widely recognised as a precursor of the “vulnerable plaque”. Contrast-enhanced ultrasound (CEUS) is a non-invasive method of imaging carotid plaques and, as contrast bubbles travel wherever erythrocytes travel, they permit visualization of IPN. Prior research studies have demonstrated that CEUS can detect IPN with a high degree of accuracy (on comparison with histological plaque specimens) and have shown a relationship between extent of plaque neovessels and plaque echogenicity and between plaque neovascularization and prior cardiovascular events. However, CEUS is a relatively recently described imaging technique and there were a number of unanswered questions in this field, some of which formed the basis for study in this research Thesis. In this Thesis, research studies were conducted on human subjects using CEUS imaging to identify IPN and its determinants. The incidence and determinants of IPN in healthy asymptomatic individuals was unknown and was studied in subjects from the London Life Sciences Population (LOLIPOP) study, a large study exploring mechanisms for differences in cardiovascular disease (CVD) between South Asian and European White individuals. The study found that approximately half of all plaques contain IPN. The only variable associated with IPN presence in an adjusted analysis was Asian ethnicity. This finding potentially has significant implications as it may help explain, in part, the greater CVD burden observed in Asian populations. A study comparing visualization of the carotid tree during B-mode and CEUS imaging was also conducted. Both IMT visualization and plaque detection were significantly improved by CEUS, implying that CEUS is superior to B-mode imaging for detection of sub-clinical atherosclerosis. Radiotherapy (RT) damages arterial walls and promotes atherosclerosis. The carotid arteries frequently receive significant incidental doses of radiation during RT treatment of head and neck cancers. The effect of RT on plaque composition – specifically IPN – had not been studied and thus a collaborative cardio-oncological study was conducted to assess the effects of RT upon IPN in cancer survivors who had previously received RT. A significant association between RT and IPN was found which may provide insights into the mechanisms underlying the increased stroke risk amongst cancer survivors treated by RT. Finally, a collaboration with biophysicists was formed to develop and validate a novel algorithm for quantitative analysis of IPN. Patients clinically scheduled to undergo carotid endarterectomy were recruited and underwent CEUS imaging prior to surgery. This study did not achieve its principal aims due to challenges with patient recruitment, challenges in image quality and with the quantification software also. Future directions of study in this promising field have been addressed in the thesis summary.Open Acces

Intravascular Ultrasound

Intravascular ultrasound (IVUS) is a cardiovascular imaging technology using a specially designed catheter with a miniaturized ultrasound probe for the assessment of vascular anatomy with detailed visualization of arterial layers. Over the past two decades, this technology has developed into an indispensable tool for research and clinical practice in cardiovascular medicine, offering the opportunity to gather diagnostic information about the process of atherosclerosis in vivo, and to directly observe the effects of various interventions on the plaque and arterial wall. This book aims to give a comprehensive overview of this rapidly evolving technique from basic principles and instrumentation to research and clinical applications with future perspectives

Ultrasound Imaging

In this book, we present a dozen state of the art developments for ultrasound imaging, for example, hardware implementation, transducer, beamforming, signal processing, measurement of elasticity and diagnosis. The editors would like to thank all the chapter authors, who focused on the publication of this book

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

Ultrasonic Pulse Wave Imaging for in vivo Assessment of Vascular Wall Dynamics and Characterization of Arterial Pathologies

Arterial diseases such as hypertension, carotid stenosis, and abdominal aortic aneurysm (AAA) may progress silently without symptoms and contribute to acute cardiovascular events such as heart attack, stroke, and aneurysm rupture, which are consistently among the leading causes of death worldwide. The arterial pulse wave, regarded as one of the fundamental vital signs of clinical medicine, originates from the heart and propagates throughout the arterial tree as a pressure, flow velocity, and wall displacement wave, giving rise to the natural pulsation of the arteries. The dynamic properties of the pulse wave are intimately related to the physical state of the cardiovascular system. Thus, the assessment of the arterial wall dynamics driven by the pulse wave may provide valuable insights into vascular mechanical properties for the early detection and characterization of arterial pathologies. The focus of this dissertation was to develop and clinically implement Pulse Wave Imaging (PWI), an ultrasound elasticity imaging-based method for the visualization and spatio-temporal mapping of the pulse wave propagation at any accessible arterial location. Motion estimation algorithms based on cross-correlation of the ultrasound radio-frequency (RF) signals were used to track the arterial walls and capture the pulse wave-induced displacements over the cardiac cycle. PWI facilitates the image-guided measurement of clinically relevant pulse wave features such as propagation speed (pulse wave velocity, or PWV), uniformity, and morphology as well as derivation of the pulse pressure waveform. A parametric study investigating the performance of PWI in two canine aortas ex vivo and 10 normal, healthy human arteries in vivo established the optimal image acquisition and signal processing parameters for reliable measurement of the PWV and wave propagation uniformity. Using this framework, three separate clinical feasibility studies were conducted in patients diagnosed with hypertension, AAA, and carotid stenosis. In a pilot study comparing hypertensive and aneurysmal abdominal aortas with normal controls, the AAA group exhibited significantly higher PWV and lower wave propagation uniformity. A “teetering” motion upon pulse wave arrival was detected in the smaller aneurysms ( 5.5 cm in diameter). While no significant difference in PWV or propagation uniformity was observed between normal and hypertensive aortas, qualitative differences in the pulse wave morphology along the imaged aortic segment may be an indicator of increased wave reflection caused by elevated blood pressure and/or arterial stiffness. Pulse Wave Ultrasound Manometry (PWUM) was introduced as an extension of the PWI method for the derivation of the pulse pressure (PP) waveform in large central arteries. A feasibility study in 5 normotensive, 9 pre-hypertensive, and 5 hypertensive subjects indicated that a significantly higher PP in the hypertensive group was detected in the abdominal aorta by PWUM but not in the peripheral arteries by alternative devices (i.e. a radial applanation tonometer and the brachial sphygmomanometer cuff). A relatively strong positive correlation between aortic PP and both radial and brachial PP was observed in the hypertensive group but not in the normal and pre-hypertensive groups, confirming the notion that PP variation throughout the arterial tree may not be uniform in relatively compliant arteries. The application of PWI in 10 stenotic carotid arteries identified phenomenon such as wave convergence, elevated PWV, and decreased cumulative displacement around and/or within regions of atherosclerotic plaque. Intra-plaque mapping of the PWV and cumulative strain demonstrated the potential to quantitatively differentiate stable (i.e. calcified) and vulnerable (i.e. lipid) plaque components. The lack of correlation between quantitative measurements (PWV, modulus, displacement, and strain) and expected plaque stiffness illuminates to need to consider several physiological and imaging-related factors such as turbulent flow, wave reflection, imaging location, and the applicability of established theoretical models in vivo. PWI presents a highly translational method for visualization of the arterial pulse wave and the image-guided measurement of several clinically relevant pulse wave features. The aforementioned findings collectively demonstrated the potential of PWI to detect, diagnose, and characterize vascular disease based on qualitative and quantitative information about arterial wall dynamics under pathological conditions

Ultrasound Imaging

This book provides an overview of ultrafast ultrasound imaging, 3D high-quality ultrasonic imaging, correction of phase aberrations in medical ultrasound images, etc. Several interesting medical and clinical applications areas are also discussed in the book, like the use of three dimensional ultrasound imaging in evaluation of Asherman's syndrome, the role of 3D ultrasound in assessment of endometrial receptivity and follicular vascularity to predict the quality oocyte, ultrasound imaging in vascular diseases and the fetal palate, clinical application of ultrasound molecular imaging, Doppler abdominal ultrasound in small animals and so on