2-D and 3-D high frame-rate Pulse Wave Imaging for the characterization of focal vascular disease

Cardiovascular diseases are major causes of morbidity and mortality in Western-style populations. Atherosclerosis and Abdominal Aortic Aneurysms (AAAs) are two prevalent vascular diseases that may progress without symptoms and contribute to acute cardiovascular events such as stroke and AAA rupture, which are consistently among the leading causes of death worldwide. The imaging methods used in the diagnosis of these diseases, have been reported to present several limitations. Given that both are associated with mechanical changes in the arterial wall, imaging of the arterial mechanical properties may improve early disease detection and patient care. Pulse wave velocity (PWV) refers to the velocity at which arterial waves generated by ventricular ejection travel along the arterial tree. PWV is a surrogate marker of arterial stiffness linked to cardiovascular mortality. The foot-to-foot method that is typically used to calculate PWV suffers from errors of distance measurements and time-delay measurements. Additionally, a single PWV estimate is provided over a relatively long distance, thus inherently lacking the capability to provide regional arterial stiffness measurements. Pulse Wave Imaging (PWI) is a noninvasive, ultrasound-based technique for imaging the propagation of pulse waves along the wall of major arteries and providing a regional PWV value for the imaged artery. The aim of this work was to enable PWI to provide more localized PWV and stiffness measurements within the imaged arterial segment and to further extend it into a 2-D and 3-D technique for the detection and monitoring of focal vascular disease at high temporal and spatial resolution. The improved modality was integrated with blood flow imaging modalities aiming to render PWI a comprehensive methodology for the study of arterial biomechanics in vivo. Spatial information was increased with the introduction of piecewise PWI. This novel technique was used to measure PWV within small sub-regions of the imaged vessel in murine aneurysmal (n = 8) and atherosclerotic aortas (n = 11) in vivo. It provided PWV and stiffness maps while capturing the progressive arterial stiffening caused by atherosclerosis. PWI was further augmented with a sophisticated adaptive algorithm, enabling it to optimally partition the imaged artery into relatively homogeneous segments, automatically isolating arterial stiffness inhomogeneities. Adaptive PWI was validated in silicone phantoms consisting of segments of varying stiffness and then tested in murine aortas in vivo. Subsequently, the conventional tradeoff between spatial and temporal resolution was addressed with a plane wave compounding implementation of PWI, allowing the acquisition of full field of view frames at over 2000 Hz. A GPU-accelerated PWI post-processing framework was developed for the processing of the big bulk of generated data. The parameters of coherent compounding were optimized in vivo. The optimized sequences were then used in the clinic to assess the mechanical properties of atherosclerotic carotids (n=10) and carotids of patients after endarterectomy (n=7), a procedure to remove the plaque and restore blood flow to the brain. In the case of atherosclerotic patients undergoing carotid endarterectomy, the results were compared against the histology of the excised plaques. Investigation of the mechanical properties of plaques was also conducted for the first time with a high-frequency transducer (18.5 MHz). Additionally, 4-D PWI was introduced, utilizing high frame rate 3-D plane wave acquisitions with a 2-D matrix array transducer (16x16 elements, 2.5 MHz). A novel methodology for PWV estimation along the direction of pulse wave propagation was implemented and validated in silicone phantoms. 4-D PWI provided comprehensive views of the pulse wave propagation in a plaque phantom and the results were compared against conventional PWI. Finally, its feasibility was tested in the carotid arteries of healthy human subjects (n=6). PWVs derived in 3-D were within the physiological range and showed good agreement with the results of conventional PWI. Finally, PWI was integrated with flow imaging modalities (Color and Vector Doppler). Thus, full field-of-view, high frame-rate, simultaneous and co-localized imaging of the arterial wall dynamics and color flow as well as 2-D vector flow was implemented. The feasibility of both techniques was tested in healthy subjects (n=6) in vivo. The relationship between the timings of the flow and wall velocities was investigated at multiple locations of the imaged artery. Vector flow velocities were found to be aligned with the vessel’s centerline during peak systole in the common carotid artery and interesting flow patterns were revealed in the case of the carotid bifurcation Consequently, with the aforementioned improvements and the inclusion of 3-D imaging, PWI is expected to provide comprehensive information on the mechanical properties of pathological arteries, providing clinicians with a powerful tool for the early detection of vascular abnormalities undetectable on the B-mode, while also enabling the monitoring of fully developed vascular pathology and of the recovery of post-operated vessels

Tracked 3D ultrasound and deep neural network-based thyroid segmentation reduce interobserver variability in thyroid volumetry

Thyroid volumetry is crucial in the diagnosis, treatment, and monitoring of thyroid diseases. However, conventional thyroid volumetry with 2D ultrasound is highly operator-dependent. This study compares 2D and tracked 3D ultrasound with an automatic thyroid segmentation based on a deep neural network regarding inter- and intraobserver variability, time, and accuracy. Volume reference was MRI. 28 healthy volunteers (24—50 a) were scanned with 2D and 3D ultrasound (and by MRI) by three physicians (MD 1, 2, 3) with different experience levels (6, 4, and 1 a). In the 2D scans, the thyroid lobe volumes were calculated with the ellipsoid formula. A convolutional deep neural network (CNN) automatically segmented the 3D thyroid lobes. 26, 6, and 6 random lobe scans were used for training, validation, and testing, respectively. On MRI (T1 VIBE sequence) the thyroid was manually segmented by an experienced MD. MRI thyroid volumes ranged from 2.8 to 16.7ml (mean 7.4, SD 3.05). The CNN was trained to obtain an average Dice score of 0.94. The interobserver variability comparing two MDs showed mean differences for 2D and 3D respectively of 0.58 to 0.52ml (MD1 vs. 2), −1.33 to −0.17ml (MD1 vs. 3) and −1.89 to −0.70ml (MD2 vs. 3). Paired samples t-tests showed significant differences for 2D (p = .140, p = .002 and p = .002) and none for 3D (p = .176, p = .722 and p = .057). Intraobsever variability was similar for 2D and 3D ultrasound. Comparison of ultrasound volumes and MRI volumes showed a significant difference for the 2D volumetry of all MDs (p = .002, p = .009, p <.001), and no significant difference for 3D ultrasound (p = .292, p = .686, p = 0.091). Acquisition time was significantly shorter for 3D ultrasound. Tracked 3D ultrasound combined with a CNN segmentation significantly reduces interobserver variability in thyroid volumetry and increases the accuracy of the measurements with shorter acquisition times

Foetal echocardiographic segmentation

Congenital heart disease affects just under one percentage of all live births [1]. Those defects that manifest themselves as changes to the cardiac chamber volumes are the motivation for the research presented in this thesis. Blood volume measurements in vivo require delineation of the cardiac chambers and manual tracing of foetal cardiac chambers is very time consuming and operator dependent. This thesis presents a multi region based level set snake deformable model applied in both 2D and 3D which can automatically adapt to some extent towards ultrasound noise such as attenuation, speckle and partial occlusion artefacts. The algorithm presented is named Mumford Shah Sarti Collision Detection (MSSCD). The level set methods presented in this thesis have an optional shape prior term for constraining the segmentation by a template registered to the image in the presence of shadowing and heavy noise. When applied to real data in the absence of the template the MSSCD algorithm is initialised from seed primitives placed at the centre of each cardiac chamber. The voxel statistics inside the chamber is determined before evolution. The MSSCD stops at open boundaries between two chambers as the two approaching level set fronts meet. This has significance when determining volumes for all cardiac compartments since cardiac indices assume that each chamber is treated in isolation. Comparison of the segmentation results from the implemented snakes including a previous level set method in the foetal cardiac literature show that in both 2D and 3D on both real and synthetic data, the MSSCD formulation is better suited to these types of data. All the algorithms tested in this thesis are within 2mm error to manually traced segmentation of the foetal cardiac datasets. This corresponds to less than 10% of the length of a foetal heart. In addition to comparison with manual tracings all the amorphous deformable model segmentations in this thesis are validated using a physical phantom. The volume estimation of the phantom by the MSSCD segmentation is to within 13% of the physically determined volume

Morphological segmentation analysis and texture-based support vector machines classification on mice liver fibrosis microscopic images

Background To reduce the intensity of the work of doctors, pre-classification work needs to be issued. In this paper, a novel and related liver microscopic image classification analysis method is proposed. Objective For quantitative analysis, segmentation is carried out to extract the quantitative information of special organisms in the image for further diagnosis, lesion localization, learning and treating anatomical abnormalities and computer-guided surgery. Methods in the current work, entropy based features of microscopic fibrosis mice’ liver images were analyzed using fuzzy c-cluster, k-means and watershed algorithms based on distance transformations and gradient. A morphological segmentation based on a local threshold was deployed to determine the fibrosis areas of images. Results the segmented target region using the proposed method achieved high effective microscopy fibrosis images segmenting of mice liver in terms of the running time, dice ratio and precision. The image classification experiments were conducted using Gray Level Co-occurrence Matrix (GLCM). The best classification model derived from the established characteristics was GLCM which performed the highest accuracy of classification using a developed Support Vector Machine (SVM). The training model using 11 features was found to be as accurate when only trained by 8 GLCMs. Conclusion The research illustrated the proposed method is a new feasible research approach for microscopy mice liver image segmentation and classification using intelligent image analysis techniques. It is also reported that the average computational time of the proposed approach was only 2.335 seconds, which outperformed other segmentation algorithms with 0.8125 dice ratio and 0.5253 precision

Évaluation de la biomécanique cardiovasculaire par élastographie ultrasonore non-invasive

L’élastographie est une technique d’imagerie qui vise à cartographier in vivo les propriétés mécaniques des tissus biologiques dans le but de fournir des informations diagnostiques additionnelles. Depuis son introduction en imagerie ultrasonore dans les années 1990, l’élastographie a trouvé de nombreuses applications. Cette modalité a notamment été utilisée pour l’étude du sein, du foie, de la prostate et des artères par imagerie ultrasonore, par résonance magnétique ou en tomographie par cohérence optique. Dans le contexte des maladies cardiovasculaires, cette modalité a un fort potentiel diagnostique puisque l’athérosclérose modifie la structure des tissus biologiques et leurs propriétés mécaniques bien avant l’apparition de tout symptôme. Quelle que soit la modalité d’imagerie utilisée, l’élastographie repose sur : l’excitation mécanique du tissu (statique ou dynamique), la mesure de déplacements et de déformations induites, et l’inversion qui permet de recouvrir les propriétés mécaniques des tissus sous-jacents. Cette thèse présente un ensemble de travaux d’élastographie dédiés à l’évaluation des tissus de l’appareil cardiovasculaire. Elle est scindée en deux parties. La première partie intitulée « Élastographie vasculaire » s’intéresse aux pathologies affectant les artères périphériques. La seconde, intitulée « Élastographie cardiaque », s’adresse aux pathologies du muscle cardiaque. Dans le contexte vasculaire, l’athérosclérose modifie la physiologie de la paroi artérielle et, de ce fait, ses propriétés biomécaniques. La première partie de cette thèse a pour objectif principal le développement d’un outil de segmentation et de caractérisation mécanique des composantes tissulaires (coeur lipidique, tissus fibreux et inclusions calciques) de la paroi artérielle, en imagerie ultrasonore non invasive, afin de prédire la vulnérabilité des plaques. Dans une première étude (Chapitre 5), nous présentons un nouvel estimateur de déformations, associé à de l’imagerie ultrarapide par ondes planes. Cette nouvelle méthode d’imagerie permet d’augmenter les performances de l’élastographie non invasive. Dans la continuité de cette étude, on propose une nouvelle méthode d’inversion mécanique dédiée à l’identification et à la quantification des propriétés mécaniques des tissus de la paroi (Chapitre 6). Ces deux méthodes sont validées in silico et in vitro sur des fantômes d’artères en polymère. Dans le contexte cardiaque, les ischémies et les infarctus causés par l’athérosclérose altèrent la contractilité du myocarde et, de ce fait, sa capacité à pomper le sang dans le corps (fonction myocardique). En échocardiographie conventionnelle, on évalue généralement la fonction myocardique en analysant la dynamique des mouvements ventriculaires (vitesses et déformations du myocarde). L’abscence de contraintes physiologiques agissant sur le myocarde (contrairement à la pression sanguine qui contraint la paroi vasculaire) ne permet pas de résoudre le problème inverse et de retrouver les propriétés mécaniques du tissu. Le terme d’élastographie fait donc ici référence à l’évaluation de la dynamique des mouvements et des déformations et non à l’évaluation des propriétés mécanique du tissu. La seconde partie de cette thèse a pour principal objectif le développement de nouveaux outils d’imagerie ultrarapide permettant une meilleure évaluation de la dynamique du myocarde. Dans une première étude (Chapitre 7), nous proposons une nouvelle approche d’échocardiographie ultrarapide et de haute résolution, par ondes divergentes, couplée à de l'imagerie Doppler tissulaire. Cette combinaison, validée in vitro et in vivo, permet d’optimiser le contraste des images mode B ainsi que l’estimation des vitesses Doppler tissulaires. Dans la continuité de cette première étude, nous proposons une nouvelle méthode d’imagerie des vecteurs de vitesses tissulaires (Chapitre 8). Cette approche, validée in vitro et in vivo, associe les informations de vitesses Doppler tissulaires et le mode B ultrarapide de l’étude précédente pour estimer l’ensemble du champ des vitesses 2D à l’intérieur du myocarde.Elastography is an imaging technique that aims to map the in vivo mechanical properties of biological tissues in order to provide additional diagnostic information. Since its introduction in ultrasound imaging in the 1990s, elastography has found many applications. This method has been used for the study of the breast, liver, prostate and arteries by ultrasound imaging, magnetic resonance imaging (MRI) or optical coherence tomography (OCT). In the context of cardiovascular diseases (CVD), this modality has a high diagnostic potential as atherosclerosis, a common pathology causing cardiovascular diseases, changes the structure of biological tissues and their mechanical properties well before any symptoms appear. Whatever the imaging modality, elastography is based on: the mechanical excitation of the tissue (static or dynamic), the measurement of induced displacements and strains, and the inverse problem allowing the quantification of the mechanical properties of underlying tissues. This thesis presents a series of works in elastography for the evaluation of cardiovascular tissues. It is divided into two parts. The first part, entitled « Vascular elastography » focuses on diseases affecting peripheral arteries. The second, entitled « Cardiac elastography » targets heart muscle pathologies. In the vascular context, atherosclerosis changes the physiology of the arterial wall and thereby its biomechanical properties. The main objective of the first part of this thesis is to develop a tool that enables the segmentation and the mechanical characterization of tissues (necrotic core, fibrous tissues and calcium inclusions) in the vascular wall of the peripheral arteries, to predict the vulnerability of plaques. In a first study (Chapter 5), we propose a new strain estimator, associated with ultrafast plane wave imaging. This new imaging technique can increase the performance of the noninvasive elastography. Building on this first study, we propose a new inverse problem method dedicated to the identification and quantification of the mechanical properties of the vascular wall tissues (Chapter 6). These two methods are validated in silico and in vitro on polymer phantom mimicking arteries. In the cardiac context, myocardial infarctions and ischemia caused by atherosclerosis alter myocardial contractility. In conventional echocardiography, the myocardial function is generally evaluated by analyzing the dynamics of ventricular motions (myocardial velocities and deformations). The abscence of physiological stress acting on the myocardium (as opposed to the blood pressure which acts the vascular wall) do not allow the solving the inverse problem and to find the mechanical properties of the fabric. Elastography thus here refers to the assessment of motion dynamics and deformations and not to the evaluation of mechanical properties of the tissue. The main objective of the second part of this thesis is to develop new ultrafast imaging tools for a better evaluation of the myocardial dynamics. In a first study (Chapter 7), we propose a new approach for ultrafast and high-resolution echocardiography using diverging waves and tissue Doppler. This combination, validated in vitro and in vivo, optimize the contrast in B-mode images and the estimation of myocardial velocities with tissue Doppler. Building on this study, we propose a new velocity vector imaging method (Chapter 8). This approach combines tissue Doppler and ultrafast B-mode of the previous study to estimate 2D velocity fields within the myocardium. This original method was validated in vitro and in vivo on six healthy volunteers

Doctor of Philosophy

dissertationCongenital heart defects are classes of birth defects that affect the structure and function of the heart. These defects are attributed to the abnormal or incomplete development of a fetal heart during the first few weeks following conception. The overall detection rate of congenital heart defects during routine prenatal examination is low. This is attributed to the insufficient number of trained personnel in many local health centers where many cases of congenital heart defects go undetected. This dissertation presents a system to identify congenital heart defects to improve pregnancy outcomes and increase their detection rates. The system was developed and its performance assessed in identifying the presence of ventricular defects (congenital heart defects that affect the size of the ventricles) using four-dimensional fetal chocardiographic images. The designed system consists of three components: 1) a fetal heart location estimation component, 2) a fetal heart chamber segmentation component, and 3) a detection component that detects congenital heart defects from the segmented chambers. The location estimation component is used to isolate a fetal heart in any four-dimensional fetal echocardiographic image. It uses a hybrid region of interest extraction method that is robust to speckle noise degradation inherent in all ultrasound images. The location estimation method's performance was analyzed on 130 four-dimensional fetal echocardiographic images by comparison with manually identified fetal heart region of interest. The location estimation method showed good agreement with the manually identified standard using four quantitative indexes: Jaccard index, Sørenson-Dice index, Sensitivity index and Specificity index. The average values of these indexes were measured at 80.70%, 89.19%, 91.04%, and 99.17%, respectively. The fetal heart chamber segmentation component uses velocity vector field estimates computed on frames contained in a four-dimensional image to identify the fetal heart chambers. The velocity vector fields are computed using a histogram-based optical flow technique which is formulated on local image characteristics to reduces the effect of speckle noise and nonuniform echogenicity on the velocity vector field estimates. Features based on the velocity vector field estimates, voxel brightness/intensity values, and voxel Cartesian coordinate positions were extracted and used with kernel k-means algorithm to identify the individual chambers. The segmentation method's performance was evaluated on 130 images from 31 patients by comparing the segmentation results with manually identified fetal heart chambers. Evaluation was based on the Sørenson-Dice index, the absolute volume difference and the Hausdorff distance, with each resulting in per patient average values of 69.92%, 22.08%, and 2.82 mm, respectively. The detection component uses the volumes of the identified fetal heart chambers to flag the possible occurrence of hypoplastic left heart syndrome, a type of congenital heart defect. An empirical volume threshold defined on the relative ratio of adjacent fetal heart chamber volumes obtained manually is used in the detection process. The performance of the detection procedure was assessed by comparison with a set of images with confirmed diagnosis of hypoplastic left heart syndrome and a control group of normal fetal hearts. Of the 130 images considered 18 of 20 (90%) fetal hearts were correctly detected as having hypoplastic left heart syndrome and 84 of 110 (76.36%) fetal hearts were correctly detected as normal in the control group. The results show that the detection system performs better than the overall detection rate for congenital heart defect which is reported to be between 30% and 60%

Automatic whole heart segmentation based on image registration

Whole heart segmentation can provide important morphological information of the heart, potentially enabling the development of new clinical applications and the planning and guidance of cardiac interventional procedures. This information can be extracted from medical images, such as these of magnetic resonance imaging (MRI), which is becoming a routine modality for the determination of cardiac morphology. Since manual delineation is labour intensive and subject to observer variation, it is highly desirable to develop an automatic method. However, automating the process is complicated by the large shape variation of the heart and limited quality of the data. The aim of this work is to develop an automatic and robust segmentation framework from cardiac MRI while overcoming these difficulties. The main challenge of this segmentation is initialisation of the substructures and inclusion of shape constraints. We propose the locally affine registration method (LARM) and the freeform deformations with adaptive control point status to tackle the challenge. They are applied to the atlas propagation based segmentation framework, where the multi-stage scheme is used to hierarchically increase the degree of freedom. In this segmentation framework, it is also needed to compute the inverse transformation for the LARM registration. Therefore, we propose a generic method, using Dynamic Resampling And distance Weighted interpolation (DRAW), for inverting dense displacements. The segmentation framework is validated on a clinical dataset which includes nine pathologies. To further improve the nonrigid registration against local intensity distortions in the images, we propose a generalised spatial information encoding scheme and the spatial information encoded mutual information (SIEMI) registration. SIEMI registration is applied to the segmentation framework to improve the accuracy. Furthermore, to demonstrate the general applicability of SIEMI registration, we apply it to the registration of cardiac MRI, brain MRI, and the contrast enhanced MRI of the liver. SIEMI registration is shown to perform well and achieve significantly better accuracy compared to the registration using normalised mutual information

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