Quantitative characterization of viscoelastic behavior in tissue-mimicking phantoms and ex vivo animal tissues.

Viscoelasticity of soft tissue is often related to pathology, and therefore, has become an important diagnostic indicator in the clinical assessment of suspect tissue. Surgeons, particularly within head and neck subsites, typically use palpation techniques for intra-operative tumor detection. This detection method, however, is highly subjective and often fails to detect small or deep abnormalities. Vibroacoustography (VA) and similar methods have previously been used to distinguish tissue with high-contrast, but a firm understanding of the main contrast mechanism has yet to be verified. The contributions of tissue mechanical properties in VA images have been difficult to verify given the limited literature on viscoelastic properties of various normal and diseased tissue. This paper aims to investigate viscoelasticity theory and present a detailed description of viscoelastic experimental results obtained in tissue-mimicking phantoms (TMPs) and ex vivo tissues to verify the main contrast mechanism in VA and similar imaging modalities. A spherical-tip micro-indentation technique was employed with the Hertzian model to acquire absolute, quantitative, point measurements of the elastic modulus (E), long term shear modulus (η), and time constant (τ) in homogeneous TMPs and ex vivo tissue in rat liver and porcine liver and gallbladder. Viscoelastic differences observed between porcine liver and gallbladder tissue suggest that imaging modalities which utilize the mechanical properties of tissue as a primary contrast mechanism can potentially be used to quantitatively differentiate between proximate organs in a clinical setting. These results may facilitate more accurate tissue modeling and add information not currently available to the field of systems characterization and biomedical research

Localized harmonic motion imaging

Localized Harmonic Motion (LHM) Imaging is a new technique of ultrasound imaging which uses the localized stimulus of the oscillatory ultrasonic radiation force as produced by a modulated signal, and estimates the resulting harmonic displacement in the tissue in order to assess its underlying mechanical properties. This method can be highly localized and is considered as a non-invasive modality. In this thesis we first present the background information for LHM imaging and we compare this technique to other tissue mechanical properties imaging techniques. We then describe a setup for LHM induction and how the data is acquired and processed. We first focus on the transducer configuration, its characteristics and the housing built to combine the transducers, then the alignment of these transducers so they are confocal and can induce and detect motion in tissues, and finally we describe the local harmonic motion experiment setup including a supporting system and the induction/detection module. One of the most critical stages is the acquisition of the signal, since signals acquired by the imaging transducer always contain different sources of noise such as acoustic (standing waves, reflection from the tank, mechanical cross-talk between the transducers) and electric noise (electric cross-talk, noise of the high power amplifier) that we need to filter. Electronic filters were designed and implemented into our LHM experiment system. Additionally, digital filters were designed to further improve the performance of the system. We applied several kinds of digital notch filters (finite impulse response (FIR) and infinite impulse response (IIR) classes) and conduct analysis on the performance when obtaining LHM displacement information. After finishing the filtering and the setup, we performed LHM displacement experiments. We analyzed the obtained displacements as well as the noise observed in the final displacement waveforms, and the influence of analog and digital filters on the displacement detection. We finally measured the displacements induced by LHM on samples with different Young modulus and were able to differentiate them by the amplitude of the motion. Finally, we performed optimizations on the algorithm for LHM displacement calculations. Due to the large amount (462) of RF signals, it will typically take around 1h for a 41x41 points image. It was found that the digital filter was the most time consuming part of the processing and it was parallelized using graphics processing unit (GPU)

Real-time quantitative sonoelastography in an ultrasound research system

Quantitative Sono-Elastographie ist eine neue Technologie für die Ultraschall Bildgebung, die Radiologen maligne Tumoren ohne Risiko der strahlungsinduzierten Krebs (d.h. Mammographie) zu erfassen können. Aufgrund gefunden Rechenkomplexität in der aktuellen Algorithmen, Implementierung von Echtzeit-Anwendungen, die Prüfungsverfahren profitieren wurde jedoch noch nicht berichtet. Zusätzlich, aktuelle Schätzer für die Darstellung eine Elastizität Bilder vorhanden Artefakte der hohen Schätzung Varianz, die die Techniker in die Gegenwart steifer Massen irreführen könnten und zwar, falsch-positive Diagnose zu erzeugen. In dieser Arbeit wird eine GPU-basierte Elastographie-System entwickelt und an einem Forschungsultraschallgeräten implementiert. Quantitative Elastizität in Echtzeit bei 2 FPS mit einer Verbesserung Rechenzeitfaktor aus 26 wird gezeigt. Validierung der Systemgenauigkeit Anzeige wurde, auf Gelatinebasis Gewebe Phantome durchgeführt., waren niedrige Vorspannung der Elastizitätswerte berichtet wurde (4,7 %) bei geringe Anregungsfrequenzen nachahmt. Ausserdem wird eine neue Elastizität Schätzer auf quantitative Sono-Elastographie basiert eingeführt. Ein lineares Problem wurde entlang der seitlichen Abmessung modelliert und eine Regularisierung Methode wurde implementieren. Elastizität Bilder mit niedriger Vorspannung wurde darstellen (1,48 %) sowie seine Leistung in einer Brust kalibrierte Phantom mit verbesserter CNR (47,3 dB) im Vergleich mit anderen Schätzer ausgewertet sowie die Verringerung Seiten Artefakte bereits erwähnt in der Literatur (PD: 22,7 dB, 1DH 28,7 dB) gefunden. Diese zwei Beitrag profitieren, die Umsetzung und Entwicklung weiterer Elastographie Techniken, die eine verbesserte Qualität der Elastizität Bilder liefern könnten und somit eine verbesserte Genauigkeit der Diagnose.Quantitative sonoelastography is an alternative technology for ultrasound imaging that helps radiologist to diagnose malignant tumors with no risk of radiation-induced cancer (i.e. mammography). However, due to the high computational complexity found in the current algorithms, implementation of real-time systems that could benefit examination procedures has not been yet reported. Additionally, elasticity maps depicted from current estimators feature artifacts of high estimation variance that could mislead the technician into the presence of stiffer masses, generating false positive diagnosis. In this thesis, a GPU-based elastography system was designed and implemented on a research ultrasound equipment, displaying quantitative elasticity in real-time at 2 FPS with an improvement computational time factor of 26. Validation of the system accuracy was conducted on gelatin-based tissue mimicking phantoms, where low bias of elasticity values were reported (4.7%) at low excitation frequencies. Additionally, a new elasticity estimator based on quantitative sonoelastography was developed. A linear problem was modeled from the acquired sonolastography data along the lateral dimension and a regularization method was implemented. The resulting elasticity images presented low bias (1.48%), enhanced CNR and reduced lateral artifacts when evaluating the algorithm’s performance in a breast calibrated phantom and comparing it with other estimators found in the literature. These two contribution benefit the implementation and development of further elastography techniques that could provide enhanced quality of elasticity images and thus, improved accuracy of diagnosis.Tesi

Development of a Harmonic Motion Imaging guided Focused Ultrasound system for breast tumor characterization and treatment monitoring

Breast cancer is the most common cancer and the second leading cause of cancer death among women. About 1 in 8 U.S. women (about 12%) will develop invasive breast cancer over the course of their lifetime. Existing methods of early detection of breast cancer include mammography and palpation, either by patient self-examination or clinical breast exam. Palpation is the manual detection of differences in tissue stiffness between breast tumors and normal breast tissue. The success of palpation relies on the fact that the stiffness of breast tumors is often an order of magnitude greater than that of normal breast tissue, i.e., breast lesions feel ''hard'' or ''lumpy'' as compared to normal breast tissue. A mammogram is an x-ray that allows a qualified specialist to examine the breast tissue for any suspicious areas. Mammography is less likely to reveal breast tumors in women younger than 50 years with denser breast than in older women. When a suspicious site is detected in the breast through a breast self-exam or on a screening mammogram, the doctor may request an ultrasound of the breast tissue. A breast ultrasound can provide evidence about whether the lump is a solid mass, a cyst filled with fluid, or a combination of the two. An invasive needle biopsy is the only diagnostic procedure that can definitely determine if the suspicious area is cancerous. In the clinic, 80% of women who have a breast biopsy do not have breast cancer. Most women with breast cancer diagnosed will have some type of surgery to remove the tumor. Depending on the type of breast cancer and how advanced it is, the patient might need other types of treatment as well, such as chemotherapy and radiation therapy. Image-guided minimally-invasive treatment of localized breast tumor as an alternative to traditional breast surgery, such as high intensity focused ultrasound (HIFU) treatment, has become a subject of intensive research. HIFU applies extreme high temperatures to induce irreversible cell injury, tumor apoptosis and coagulative necrosis. Compared with conventional surgical procedures the main advantages of HIFU ablation lie in the fact that it is non-invasive, less scarring and less painful, allowing for shorter recovery time. HIFU can be guided by MRI (MRgFUS) or by conventional diagnostic ultrasound (USgFUS). Worldwide, thousands of patients with uterine fibroids, liver cancer, breast cancer, pancreatic cancer, bone tumors, and renal cancer have been treated by USgFUS. In this dissertation, the objective is to develop an integrated Harmonic Motion Imaging guided Focused Ultrasound (HMIgFUS) system as a clinical monitoring technique for breast HIFU with the added capability of detecting tumors for treatment planning, evaluation of tissue stiffness changes during HIFU ablation for treatment monitoring in real time, and assessment of thermal lesion sizes after treatment evaluation. A new HIFU treatment planning method was described that used oscillatory radiation force induced displacement amplitude variations to detect the HIFU focal spot before lesioning. Using this method, we were able to visualize the HMIgFUS focal region at variable depths. By comparing the estimated displacement profiles with lesion locations in pathology, we demonstrated the feasibility of using this HMI-based technique to localize the HIFU focal spot and predict lesion location during the planning phase. For HIFU monitoring, a HIFU lesion detection and ablation monitoring method was first developed using oscillatory radiation force induced displacement amplitude variations in real time. Using this method, the HMIgFUS focal region and lesion formation were visualized in real time at a feedback rate of 2.4 Hz. By comparing the estimated lesion size against gross pathology, the feasibility of using HMIgFUS to monitor treatment and lesion formation without interruption is demonstrated. In order to reduce the imaging time, it is shown in this dissertation that using the steered FUS beam, HMI can be used to image a 2.3 times larger ROI without requiring physical movement of the transducer. Using steering for HMI can be used to shorten the total imaging duration without requiring physical movement of the transducer. For the application of breast tumor, HMI and HMIgFUS were optimized and applied to ex vivo breast tissue. The results showed that HMI is experimentally capable of mapping and differentiating stiffness in normal and abnormal breast tissues. HMIgFUS can also successfully generate thermal lesions on normal and pathological breast tissues. HMI has also been applied to post-surgical breast mastectomy specimens to mimic the in vivo environment. In the end, the first HMI clinical system has been built with added capability of GUP-based parallel beamforming. A clinical trial has been approved at Columbia University to image breast tumor on patient. The HMI clinical system has shown to be able to map fibroadenoma mass on two patients with valid HMI displacement. The study in this dissertation may yield an early-detection technique for breast cancer without any age discrimination and thus, increase the survival rate

Nonlinear ultrasonic wave mixing for the non-destructive evaluation of materials' properties

Nonlinear ultrasonic wave mixing has been shown to be a powerful method to detect and characterise damage or defects in materials. This technique has been used in a wide range of applications such as the non-destructive evaluation of material properties due to its higher sensitivity when compared to conventional, linear, ultrasonic techniques. This technique is based on an investigation of nonlinear behaviours in a material by using harmonic generation or nonlinear resonance, which are able to detect small scale defects or structural degradation, such as cracks, micro cracks, and material characterisation in the wider sense. Within the context of medicine, the detection of deep tissue injury, such as a pressure ulcer, could benefit from the capabilities of nonlinear ultrasonic wave mixing methods. These wounds are currently detected late, leading to difficult treatments. Earlier detection over smaller areas based on difference, in properties relative to neighboring tissue, means nonlinear ultrasound techniques could have a significant impact on patient recovery. The purpose of this thesis is to develop a platform which can detect nonlinearities of materials using nonlinear ultrasonic wave mixing techniques. In this study, two kinds of non-linear wave mixing techniques are introduced for the detection of small particles distributed in a hydrogel phantom, a proxy for an injury area in the early stages of the development of a wound. Wave mixing was also applied to measure an accumulated change to material properties also known as physical aging. The results demonstrated an improved ability of non-linear wave mixing method over linear techniques to distinguish minuscule particles and to be able to monitor a slow rate of change in material properties, which would be used to monitor deep wounds under the skin such as pressure ulcers. The results clearly show that the summed frequency of a nonlinear wave signal can detect a range of microparticle sizes (70m, 100m and 150m) with higher sensitivity and resolution as compared to the linear echo ultrasound. This is a factor of more than 10 increase in the resolution of defect detection as compared to linear methods, allowing for earlier wound identification. In addition, the response of the nonlinear summed frequency interaction was captured with a 30 s sampling rate at 6.25 MHz.This system showed that the nonlinear ultrasonic technique was suitable to detect the physical aging of amorphous polymers at the annealing temperature. When the polymer structure underwent structural relaxation, the nonlinear wave mixing energy gradually increased due to the non-equilibrium state and then continually developed due to physical aging. The system is not only designed to detect the nonlinearities of soft material properties using nonlinear ultrasonic techniques, but also to enable its application to evaluate the accumulated change of material properties. These experimental results suggest that nonlinear ultrasonic wave mixing technique may be useful for detecting small scale (early onset of) pressure ulcers developing deep in the skin. The ability to observe physical aging in polymers, and the analogous behaviour of polymer physical aging and ulcer development, suggest it may be possible to monitor pressure ulcer development with nonlinear techniques

Modélisation de la diffraction des ondes de cisaillement en élastographie dynamique ultrasonore

L'élastographie ultrasonore est une technique d'imagerie émergente destinée à cartographier les paramètres mécaniques des tissus biologiques, permettant ainsi d’obtenir des informations diagnostiques additionnelles pertinentes. La méthode peut ainsi être perçue comme une extension quantitative et objective de l'examen palpatoire. Diverses techniques élastographiques ont ainsi été proposées pour l'étude d'organes tels que le foie, le sein et la prostate et. L'ensemble des méthodes proposées ont en commun une succession de trois étapes bien définies: l'excitation mécanique (statique ou dynamique) de l'organe, la mesure des déplacements induits (réponse au stimulus), puis enfin, l'étape dite d'inversion, qui permet la quantification des paramètres mécaniques, via un modèle théorique préétabli. Parallèlement à la diversification des champs d'applications accessibles à l'élastographie, de nombreux efforts sont faits afin d'améliorer la précision ainsi que la robustesse des méthodes dites d'inversion. Cette thèse regroupe un ensemble de travaux théoriques et expérimentaux destinés à la validation de nouvelles méthodes d'inversion dédiées à l'étude de milieux mécaniquement inhomogènes. Ainsi, dans le contexte du diagnostic du cancer du sein, une tumeur peut être perçue comme une hétérogénéité mécanique confinée, ou inclusion, affectant la propagation d'ondes de cisaillement (stimulus dynamique). Le premier objectif de cette thèse consiste à formuler un modèle théorique capable de prédire l'interaction des ondes de cisaillement induites avec une tumeur, dont la géométrie est modélisée par une ellipse. Après validation du modèle proposé, un problème inverse est formulé permettant la quantification des paramètres viscoélastiques de l'inclusion elliptique. Dans la continuité de cet objectif, l'approche a été étendue au cas d'une hétérogénéité mécanique tridimensionnelle et sphérique avec, comme objectifs additionnels, l'applicabilité aux mesures ultrasonores par force de radiation, mais aussi à l'estimation du comportement rhéologique de l'inclusion (i.e., la variation des paramètres mécaniques avec la fréquence d'excitation). Enfin, dans le cadre de l'étude des propriétés mécaniques du sang lors de la coagulation, une approche spécifique découlant de précédents travaux réalisés au sein de notre laboratoire est proposée. Celle-ci consiste à estimer la viscoélasticité du caillot sanguin via le phénomène de résonance mécanique, ici induit par force de radiation ultrasonore. La méthode, dénommée ARFIRE (''Acoustic Radiation Force Induced Resonance Elastography'') est appliquée à l'étude de la coagulation de sang humain complet chez des sujets sains et sa reproductibilité est évaluée.Ultrasound elastography is an emerging technology derived from the concept of manual palpation and dedicated to the mapping of biological tissue mechanical properties in a diagnostic context. Various elastographic approaches have been applied to the study of organs such as the liver, breast or prostate. All proposed techniques rely on a three-steps procedure: first, the tissue to be studied is mechanically excited, in a static or dynamic way. Induced displacements are then measured and used to estimate qualitatively or quantitatively mechanical properties of the medium. This step is called inversion. While application fields of elastography are constantly broadened, efforts are made to provide robust and accurate inversion algorithms. In this monography, theoretical and experimental works related to the development of new inversion methods dedicated to the study of mechanically inhomogeneous media in dynamic ultrasound elastography are provided. In the context of breast cancer diagnosis, a localized tumour can be assumed as a confined mechanical heterogeneity, also referred as an inclusion, which can disturb the propagation of shear waves (dynamic excitation). The first objective of this thesis is to provide a theoretical model to describe physical interactions occurring between incident shear waves and a tumour, here geometrically assumed as an ellipse. Once the theoretical model is validated, an inverse problem is formulated allowing further quantification of inclusion viscoelastic parameters. Aiming the development of realistic models, the previous work has been extended to the case of three dimensional spherical heterogeneities and adapted to the specific case of an acoustic radiation force excitation. Furthermore, the feasibility of assessing the medium rheological model (i.e., the frequency dependence of mechanical properties) is demonstrated. Finally, in the context of vascular diseases and blood coagulation, an inversion method based on the study of the mechanical resonance phenomenon induced by acoustic radiation force is proposed. The technique, termed ARFIRE (Acoustic Radiation Force Induced Resonance Elastography), is applied to human whole blood samples and the reproducibility of results is assessed

Noninvasive ARFI Ultrasound for Differentiating Carotid Plaque with High Stroke Risk

Stroke is the leading cause of death worldwide. Fortunately, incidence and mortality rates are declining due to the successes of pharmaceutical therapies and revascularization procedures such as carotid endarterectomy (CEA). While CEA has high efficacy for preventing stroke in patients with severe (>70%) carotid stenosis, its usefulness decreases as stroke risk declines in patients without symptoms and less severe stenosis. Clinical studies show that 13 out of 14 symptomatic patients with 50-69% stenosis, and 21 out of 22 asymptomatic patients with severe stenosis undergo CEA unnecessarily. There is an unmet need to identify vulnerable carotid plaque and indicate stroke risk.Improving the assessment of carotid plaque vulnerability could be met by analyzing plaque structure and composition. Post-mortem studies have shown that the presence of thin or ruptured fibrous caps (TRFC), lipid-rich necrotic cores (LRNC), and intraplaque hemorrhage (IPH) is associated with high stroke risk. Further, MRI studies have shown association between the presence of TRFC and IPH with previous stroke or transient ischemic attack (TIA), with increased risk of stroke conferred by TRFC, LRNC, and IPH, in human carotid plaques. While features that convey vulnerability to rupture are well known, there is currently no established low-cost, noninvasive imaging method that consistently characterizes plaque structure and composition.The project proposed herein aims to develop and evaluate Acoustic Radiation Force Impulse (ARFI)-based ultrasound techniques for delineating the structure and composition of carotid plaque in humans. First, novel ARFI imaging methods are evaluated in terms of sensitivity and specificity for detecting of calcium, collagen, lipid-rich necrotic core, and intraplaque hemorrhage in human atherosclerotic plaques in vivo. Second, an automatic classification framework is developed and compared to a human reader-based ARFI image assessment. Third, the automatic classifier performance is improved by including additional data acquisitions in the cardiac cycle, and using high frequency and harmonic tracking. Overall, this project demonstrates the efficacy of ARFI ultrasound, evaluating log(VoA) and with a machine learning-based automatic classifier, to delineate vulnerable plaque components in human carotid plaques in vivo. These findings have the potential to improve the current state of the art in clinical diagnosis and management of atherosclerosis.Doctor of Philosoph

Développement d'une nouvelle méthode de caractérisation tissulaire basée sur l'élastographie ultrasonore : application pour le dépistage précoce du cancer du sein

Le cancer du sein est le cancer le plus fréquent chez la femme. Il demeure la cause de mortalité la plus importante chez les femmes âgées entre 35 et 55 ans. Au Canada, plus de 20 000 nouveaux cas sont diagnostiqués chaque année. Les études scientifiques démontrent que l'espérance de vie est étroitement liée à la précocité du diagnostic. Les moyens de diagnostic actuels comme la mammographie, l'échographie et la biopsie comportent certaines limitations. Par exemple, la mammographie permet de diagnostiquer la présence d’une masse suspecte dans le sein, mais ne peut en déterminer la nature (bénigne ou maligne). Les techniques d’imagerie complémentaires comme l'échographie ou l'imagerie par résonance magnétique (IRM) sont alors utilisées en complément, mais elles sont limitées quant à la sensibilité et la spécificité de leur diagnostic, principalement chez les jeunes femmes (< 50 ans) ou celles ayant un parenchyme dense. Par conséquent, nombreuses sont celles qui doivent subir une biopsie alors que leur lésions sont bénignes. Quelques voies de recherche sont privilégiées depuis peu pour réduire l`incertitude du diagnostic par imagerie ultrasonore. Dans ce contexte, l’élastographie dynamique est prometteuse. Cette technique est inspirée du geste médical de palpation et est basée sur la détermination de la rigidité des tissus, sachant que les lésions en général sont plus rigides que le tissu sain environnant. Le principe de cette technique est de générer des ondes de cisaillement et d'en étudier la propagation de ces ondes afin de remonter aux propriétés mécaniques du milieu via un problème inverse préétabli. Cette thèse vise le développement d'une nouvelle méthode d'élastographie dynamique pour le dépistage précoce des lésions mammaires. L'un des principaux problèmes des techniques d'élastographie dynamiques en utilisant la force de radiation est la forte atténuation des ondes de cisaillement. Après quelques longueurs d'onde de propagation, les amplitudes de déplacement diminuent considérablement et leur suivi devient difficile voir impossible. Ce problème affecte grandement la caractérisation des tissus biologiques. En outre, ces techniques ne donnent que l'information sur l'élasticité tandis que des études récentes montrent que certaines lésions bénignes ont les mêmes élasticités que des lésions malignes ce qui affecte la spécificité de ces techniques et motive la quantification de d'autres paramètres mécaniques (e.g.la viscosité). Le premier objectif de cette thèse consiste à optimiser la pression de radiation acoustique afin de rehausser l'amplitude des déplacements générés. Pour ce faire, un modèle analytique de prédiction de la fréquence de génération de la force de radiation a été développé. Une fois validé in vitro, ce modèle a servi pour la prédiction des fréquences optimales pour la génération de la force de radiation dans d'autres expérimentations in vitro et ex vivo sur des échantillons de tissu mammaire obtenus après mastectomie totale. Dans la continuité de ces travaux, un prototype de sonde ultrasonore conçu pour la génération d'un type spécifique d'ondes de cisaillement appelé ''onde de torsion'' a été développé. Le but est d'utiliser la force de radiation optimisée afin de générer des ondes de cisaillement adaptatives, et de monter leur utilité dans l'amélioration de l'amplitude des déplacements. Contrairement aux techniques élastographiques classiques, ce prototype permet la génération des ondes de cisaillement selon des parcours adaptatifs (e.g. circulaire, elliptique,…etc.) dépendamment de la forme de la lésion. L’optimisation des dépôts énergétiques induit une meilleure réponse mécanique du tissu et améliore le rapport signal sur bruit pour une meilleure quantification des paramètres viscoélastiques. Il est aussi question de consolider davantage les travaux de recherches antérieurs par un appui expérimental, et de prouver que ce type particulier d'onde de torsion peut mettre en résonance des structures. Ce phénomène de résonance des structures permet de rehausser davantage le contraste de déplacement entre les masses suspectes et le milieu environnant pour une meilleure détection. Enfin, dans le cadre de la quantification des paramètres viscoélastiques des tissus, la dernière étape consiste à développer un modèle inverse basé sur la propagation des ondes de cisaillement adaptatives pour l'estimation des paramètres viscoélastiques. L'estimation des paramètres viscoélastiques se fait via la résolution d'un problème inverse intégré dans un modèle numérique éléments finis. La robustesse de ce modèle a été étudiée afin de déterminer ces limites d'utilisation. Les résultats obtenus par ce modèle sont comparés à d'autres résultats (mêmes échantillons) obtenus par des méthodes de référence (e.g. Rheospectris) afin d'estimer la précision de la méthode développée. La quantification des paramètres mécaniques des lésions permet d'améliorer la sensibilité et la spécificité du diagnostic. La caractérisation tissulaire permet aussi une meilleure identification du type de lésion (malin ou bénin) ainsi que son évolution. Cette technique aide grandement les cliniciens dans le choix et la planification d'une prise en charge adaptée.Breast cancer is the most frequent cancer in women and the leading cause of death for women between 35 and 55 years old. In Canada, more than 20,000 new cases are diagnosed each year. Most of the previous works have shown that life expectancy is closely related to the precocity of diagnosis. Current diagnostic imaging methods such as mammography, sonography, MRI present limitations such as irradiation (mammography), low specificity and low resolution (sonography) and high cost (MRI). For example, about 95% of abnormalities detected by mammography are proven to be benign lesions after complementary examinations (biopsy). Sonography is useful as a complementary examination but the low resolution of its images, its low specificity (54% for women less than 50 years) and its operator dependent interpretation seriously limit the use of this modality alone. MRI is a non-invasive technique with a relatively high sensitivity (86% for women below 50 years), but its limitations are the high cost and the waiting time for medical examination, which dedicate it as a monitoring technique in high-risk patients. It is therefore necessary to examine new noninvasive and cost effective methods. In this context, dynamic elastography is a promising approach. It is an emerging quantitative medical imaging technique inspired from palpation and based on the determination of elastic properties (stiffness) of tissues. This thesis aims the development of a novel dynamic ultrasound elastography method for early detection of breast lesions. One of the main problems of dynamic elastography techniques using remote palpation (acoustic radiation force) is the strong attenuation of shear waves. After few wavelengths of propagation, displacement amplitudes considerably decrease and their tracking becomes difficult even impossible. This problem greatly affects biological tissue characterization. Moreover, these techniques give only the information about elasticity while recent studies show that some benign lesions have the same elasticity as malignant lesions which affect the specificity of these techniques and motivate investigation of other physical parameters (e.g. viscosity). The first objective of this thesis is to optimize the acoustic radiation force using frequency adaptation to enhance the amplitude of displacements. An analytical model has been developed to predict the optimal frequency for the generation of the radiation force. Once validated on phantoms (in vitro), this model was used for the prediction of the optimal frequencies for the generation of the radiation force in tissue mimicking phantoms and ex vivo human breast cancer samples obtained after total mastectomy. Gains in magnitude were between 20% to158% for in vitro measurements on agar-gelatin phantoms, and 170% to 336% for ex vivo measurements on a human breast sample, depending on focus depths and attenuations of tested samples. The signal-to-noise ratio was also improved by more than four folds with adapted sequences. We conclude that frequency adaptation is a complementary technique that is efficient for the optimization of displacement amplitudes. This technique can be used safely to optimize the deposited local acoustic energy, without increasing the risk of damaging tissues and transducer elements. In the second part of this thesis, a prototype of an ultrasound probe for the generation of a specific type of adaptive shear waves called ''adaptive torsional shear waves'' has been developed. The goal was to use the optimized radiation force (developed in the first part) to generate adaptive torsional shear wave, and prove their utility in improving the amplitude of displacement. During their inward propagation, the amplitude of displacement generated by torsional shear waves was enhanced and the signal to noise ratio improved due to the constructive interferences. Torsional shear waves can also resonate heterogeneities which further enhance the displacement contrast between suspicious masses and its surrounding medium. Finally, in the context of assessment of mechanical proprieties of tissue, the last step of this thesis is to develop an inverse problem based on the propagation of adaptive torsional shear waves to estimate the viscoelastic parameters. A finite element method (FEM) model was developed to solve the inverse wave propagation problem and obtain viscoelastic properties of interrogated media. The inverse problem was formulated and solved in the frequency domain and its robustness was evaluated. The proposed model was validated in vitro with two independent rheology methods on several homogeneous and heterogeneous breast tissue mimicking phantoms over a broad range of frequencies (up to 400Hz). The obtained results were in good agreement with reference rheology methods with discrepancies between 8% and 38% for shear modulus and from 9% to 67% for loss modulus. The robustness study showed that the proposed inverse problem solution yielded a good estimation of the storage (19%) and loss moduli (32%) even with very noisy signals

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