Biomechanical Modeling and Inverse Problem Based Elasticity Imaging for Prostate Cancer Diagnosis

Early detection of prostate cancer plays an important role in successful prostate cancer treatment. This requires screening the prostate periodically after the age of 50. If screening tests lead to prostate cancer suspicion, prostate needle biopsy is administered which is still considered as the clinical gold standard for prostate cancer diagnosis. Given that needle biopsy is invasive and is associated with issues including discomfort and infection, it is desirable to develop a prostate cancer diagnosis system that has high sensitivity and specificity for early detection with a potential to improve needle biopsy outcome. Given the complexity and variability of prostate cancer pathologies, many research groups have been pursuing multi-parametric imaging approach as no single modality imaging technique has proven to be adequate. While imaging additional tissue properties increases the chance of reliable prostate cancer detection and diagnosis, selecting an additional property needs to be done carefully by considering clinical acceptability and cost. Clinical acceptability entails ease with respect to both operating by the radiologist and patient comfort. In this work, effective tissue biomechanics based diagnostic techniques are proposed for prostate cancer assessment with the aim of early detection and minimizing the numbers of prostate biopsies. The techniques take advantage of the low cost, widely available and well established TRUS imaging method. The proposed techniques include novel elastography methods which were formulated based on an inverse finite element frame work. Conventional finite element analysis is known to have high computational complexity, hence computation time demanding. This renders the proposed elastography methods not suitable for real-time applications. To address this issue, an accelerated finite element method was proposed which proved to be suitable for prostate elasticity reconstruction. In this method, accurate finite element analysis of a large number of prostates undergoing TRUS probe loadings was performed. Geometry input and displacement and stress fields output obtained from the analysis were used to train a neural network mapping function to be used for elastopgraphy imaging of prostate cancer patients. The last part of the research presented in this thesis tackles an issue with the current 3D TRUS prostate needle biopsy. Current 3D TRUS prostate needle biopsy systems require registering preoperative 3D TRUS to intra-operative 2D TRUS images. Such image registration is time-consuming while its real-time implementation is yet to be developed. To bypass this registration step, concept of a robotic system was proposed which can reliably determine the preoperative TRUS probe position relative to the prostate to place at the same position relative to the prostate intra-operatively. For this purpose, a contact pressure feedback system is proposed to ensure similar prostate deformation during 3D and 2D image acquisition in order to bypass the registration step

Ultrasound Elastography: Direct Strain Estimation

Ultrasound elastography involves measuring the mechanical properties of tissue, and has many applications in diagnostics and intervention. Ultrasound elastography techniques mainly target obtaining strain images from raw Radio-Frequency (RF) echo field produced by ultrasound machine without adding any hardware. A common step in different elastography methods is imaging the tissue while it undergoes deformation and estimating the displacement field from the images. A popular next step is to estimate tissue strain, which gives clues into the underlying tissue elasticity modulus. To estimate the strain, one should compute the gradient of the displacement image, which amplifies the noise. The noise is commonly minimized by least square estimation of the gradient from multiple displacement measurements, which reduces the noise by sacrificing image resolution. The first part of this thesis propose a new method which adaptively adjusts the level and orientation of the smoothing strain images using two different mechanisms. First, the precision of the displacement field decreases significantly in the regions with high signal decorrelation, which requires increasing the smoothness. Second, smoothing the strain field at the boundaries between different tissue types blurs the edges, which can render small targets invisible. To minimize blurring and noise, we perform anisotropic smoothing and perform smoothing parallel to the direction of the edges. The first mechanism ensures that textures/variations in the strain image reflect underlying tissue properties and are not caused by errors in the displacement estimation. The second mechanism keeps the edges between different tissue structures sharp while minimizing the noise. The second part of this thesis introduces a 2D strain imaging technique called SHORTCUT (meSHing Of gRadienT in DP for direCt Ultrasound elasTography) based on minimizing a cost function. The cost function incorporates similarity of echo amplitudes and tissue continuity. The proposed technique is fast, robust and accurate and it directly produces the strain images from RF data using a novel dynamic programming (DP) configuration. Unlike the standard DP algorithm which discretizes the decision space (displacement field) and search in the space of piecewise constant functions, the proposed DP discretizes the gradient of the decision space (strain field) and search the space of continuous piecewise linear functions. Eliminating the displacement differentiation block and performing a global search instead of local search which exist in all of the available strain estimation techniques result in substantial improvement in SNR, CNR and accuracy of the estimations. The effectiveness of the proposed methods is investigated through simulation data, phantom experiments, and in vivo patient data

Exploiting Mechanics-Based Priors for Lateral Displacement Estimation in Ultrasound Elastography

Tracking the displacement between the pre- and post-deformed radio-frequency (RF) frames is a pivotal step of ultrasound elastography, which depicts tissue mechanical properties to identify pathologies. Due to ultrasound's poor ability to capture information pertaining to the lateral direction, the existing displacement estimation techniques fail to generate an accurate lateral displacement or strain map. The attempts made in the literature to mitigate this well-known issue suffer from one of the following limitations: 1) Sampling size is substantially increased, rendering the method computationally and memory expensive. 2) The lateral displacement estimation entirely depends on the axial one, ignoring data fidelity and creating large errors. This paper proposes exploiting the effective Poisson's ratio (EPR)-based mechanical correspondence between the axial and lateral strains along with the RF data fidelity and displacement continuity to improve the lateral displacement and strain estimation accuracies. We call our techniques MechSOUL (Mechanically-constrained Second-Order Ultrasound eLastography) and L1-MechSOUL (L1-norm-based MechSOUL), which optimize L2- and L1-norm-based penalty functions, respectively. Extensive validation experiments with simulated, phantom, and in vivo datasets demonstrate that MechSOUL and L1-MechSOUL's lateral strain and EPR estimation abilities are substantially superior to those of the recently-published elastography techniques. We have published the MATLAB codes of MechSOUL and L1-MechSOUL at http://code.sonography.ai.Comment: Link to the Supplemental Video: https://drive.google.com/file/d/1uOmt-T4i9MwR98jUoMsu-eOhQ2mgjrBd/view?usp=sharin

New Image Processing Methods for Ultrasound Musculoskeletal Applications

In the past few years, ultrasound (US) imaging modalities have received increasing interest as diagnostic tools for orthopedic applications. The goal for many of these novel ultrasonic methods is to be able to create three-dimensional (3D) bone visualization non-invasively, safely and with high accuracy and spatial resolution. Availability of accurate bone segmentation and 3D reconstruction methods would help correctly interpreting complex bone morphology as well as facilitate quantitative analysis. However, in vivo ultrasound images of bones may have poor quality due to uncontrollable motion, high ultrasonic attenuation and the presence of imaging artifacts, which can affect the quality of the bone segmentation and reconstruction results. In this study, we investigate the use of novel ultrasonic processing methods that can significantly improve bone visualization, segmentation and 3D reconstruction in ultrasound volumetric data acquired in applications in vivo. Specifically, in this study, we investigate the use of new elastography-based, Doppler-based and statistical shape model-based methods that can be applied to ultrasound bone imaging applications with the overall major goal of obtaining fast yet accurate 3D bone reconstructions. This study is composed to three projects, which all have the potential to significantly contribute to this major goal. The first project deals with the fast and accurate implementation of correlation-based elastography and poroelastography techniques for real-time assessment of the mechanical properties of musculoskeletal tissues. The rationale behind this project is that, iii in the future, elastography-based features can be used to reduce false positives in ultrasonic bone segmentation methods based on the differences between the mechanical properties of soft tissues and the mechanical properties of hard tissues. In this study, a hybrid computation model is designed, implemented and tested to achieve real time performance without compromise in elastographic image quality . In the second project, a Power Doppler-based signal enhancement method is designed and tested with the intent of increasing the contrast between soft tissue and bone while suppressing the contrast between soft tissue and connective tissue, which is often a cause of false positives in ultrasonic bone segmentation problems. Both in-vitro and in-vivo experiments are performed to statistically analyze the performance of this method. In the third project, a statistical shape model based bone surface segmentation method is proposed and investigated. This method uses statistical models to determine if a curve detected in a segmented ultrasound image belongs to a bone surface or not. Both in-vitro and in-vivo experiments are performed to statistically analyze the performance of this method. I conclude this Dissertation with a discussion on possible future work in the field of ultrasound bone imaging and assessment

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

Ultrasound Elastography: Deep Learning Approach

Ultrasound elastography images the elasticity of a biological tissue. Conventional algorithms for ultrasound elastography suffer from different noises severely compromising the quality of time-delay estimation. Calculation of time-delay estimation is a key component of strain estimation. However, time-delay estimation is analogous to optical flow estimation, a classical computer vision problem. Deep learning networks have reported recent success in optical flow estimation compared to the conventional techniques. Classical ultrasound elastography algorithms have been unable to provide a single solution to both commonly known issues of noise and computation time. Deep learning techniques have a bright prospect in addressing both issues. The goal of this thesis is to investigate whether optical flow estimation is translatable to ultrasound elastography as the core nature of both of these problems are analogous. In this thesis we aim to develop and train a robust deep neural network for ultrasound elastography. First, an efficient deep learning network trained for optical flow estimation is used for time-delay estimation. The initial time-delay estimation is further fine-tuned by optimizing a global cost function for generating high quality strain images. Simulation, phantom and clinical experiments show the robustness of the deep learning approach both quantitatively and qualitatively. Next, the weights of the deep learning network are fine-tuned using transfer learning technique for transferring the efficacy of optical flow estimation to time-delay estimation. The objective is to retain the robustness introduced by the deep learning network while enhancing the overall performance of the time-delay estimation in ultrasound elastography. Simulation and experimental phantom results show that the time-delay estimation has improved slightly after fine-tuning the weights using transfer learning