Ultrassonografia (US) é usada por médicos para ajudar em diagnósticos e intervenções. Ela fornece uma visada tomográfica de órgãos internos como, por exemplo, pâncreas aorta, fígado, bexiga, rins e baço. O médico pode utilizar a US para realizar apenas uma avaliação visual ou pode também comprimir o tecido para analisar a dinâmica, uma vez que a elasticidade da lesão pode estar relacionada à patologias. Consequentemente, diversos procedimentos computacionais vem sendo desenvolvidos com o intuito de fornecer ao médico informações acerca das propriedades elásticas do tecido. Entretanto, uma avaliação completa e objetiva dos procedimentos computacionais sobre US pode ser dificultada pelo difícil acesso a imagens com as propriedades desejadas ou pela falta de padrão-ouro para ser utilizado como referência. Portanto, nós desenvolvemos uma ferramenta capaz de criar phantoms numérico que imitam a compressão induzida por um médico através de um transdutor. A deformação do tecido é baseada em método doe elementos finitos e o deslocamento dos espalhadores é calculado usando isomorfismo linear. Depois do deslocamento dos espalhadores, Field II foi utilizado para simular o ruído Speckle. Assim, foi possível a criação de uma sequência de imagens de US com deformação realística. Este método foi implementado em Matlab e está disponível para download sem custos. A deformação do phantom foi validada através da medição de contraste de compressão em phantoms de duas camadas. Uma atenção especial foi dada a doenças cardiovasculares devido ao impacto que essas patologias causam no cenário médico do Brasil e do mundo. Nas últimas décadas, a prevalência de patologias cardiovasculares têm crescido progressivamente e se tornou uma séria questão de saúde pública. Elas estão entre as maiores causas de mortes, internações e gastos com saúde. Na prática intervencionista, o ultrassom intravascular (IVUS) é utilizado para obter informações do vaso sanguíneo e de eventuais patologias. Portanto, foi desenvolvida também uma simulação numérica de phantoms de IVUS. A simulação do vaso sanguíneo também se baseou em método dos elementos finitos e isomorfismo linear. Contudo, uma simulação confiável de IVUS deve considerar o caminho do cateter no interior do vaso sanguíneo, porque isto determina a posição do transdutor. Portanto, nós desenvolvemos um novo método, baseado em equilíbrio de forças, para determinar a posição de menor energia do cateter. O método foi validado através da comparação da posição estimada com a posição de um fio-guia de aço real e apresentou erro quadrático médio e média Hausdorff menor que 1 mm para ambos. Foram utilizados dois métodos diferentes para rastrear e estimar a deformação de determinadas estruturas no tecido: Optical Flow e 2D Block Matching. Foi aplicado uma implementação inovadora de 2D Block Matching com interpolação sub-pixel linear e propagação de deslocamento. Posteriormente, a validação será feita comparando-se a o movimento estimado com o padrão-ouro numérico utilizado para construir a simulação. O 2D block matching forneceu resultados melhores que o optical flow. Após a análise em phantoms numéricos, equipamento real de ultrassom foi utilizado para aquisição de imagens modo-B de phantoms físicos. Então, nós realizamos a estimativa do movimento das estruturas para analisar as propriedades morfológicas e dinâmicas do tecidos. Os resultados obtidos foram comparados com a elastografia fornecida pelo equipamento. Em acordo com os resultados obtidos na simulação numérica, o 2D block matching novamente apresentou resultados melhores que o optical flow. Finalmente, os dois métodos de rastreamento foi aplicada em imagens simuladas de IVUS, que foram divididas em 2 conjuntos de quadros. O primeiro conjunto, S1, continha todos os quadros da sequência de IVUS e o segundo conjunto, S2, continha apenas os quadros correspondentes a uma fase específica do ciclo cardíaco. Sendo assim, foi analisado o balanço entre o impacto do movimento cardíaco e a taxa de quadros. Para os pontos localizados nas bordas dos objetos, Optical flow teve um bom desempenho para ambos S1 e S2. Em regiões homogêneas, entretanto, o optical flow foi capaz de rastrear os pontos em S2, sugerindo que é melhor o trabalho com movimento cardíaco reduzido em detrimento da taxa de quadros, tal qual a aquisição de IVUS engatilhado por ECG. Já o 2D block matching apresentou um mau rastreamento para todos os pontos selecionados. Além da simulação da aquisição de ultrassonografia com deformação e do rastreamento de estruturas, também desenvolvemos uma nova técnica de filtragem capaz de remover a textura speckle sem borrar as bordas. A técnica proposta apresentou os melhores resultados quando comparados com outros nove filtros da literatura. Foi desenvolvida também uma nova métrica que utiliza o ruído speckle da própria imagem para fornecer um parâmetro que pode ajudar o usuário a decidir o tamanho da janelo de um filtro. / Ultrasonography (US) is used by physicians to help on diagnosis and interventions. It provides tomographic views of inner organs such as pancreas, aorta, inferior vena cava, liver, gall bladder, bile ducts, kidneys and spleen. The physician may utilize US to perform only a visual assessment or may also compress the tissue to analyze its dynamics, since lesion elasticity may be related to dangerousness. Consequently, several computational procedures have been developed in order to provide information about the elastic properties of the tissue. However, a thorough and objective evaluation of US computational procedures may be hindered by the difficult access to US images with the desired features and the lack of gold-standard parameters. Therefore, we developed a tool that is able to create numeric phantom that mimics the compression induced by physician with the transducer. The tissue deformation was based on finite elements method and the displacement of the scatterers were calculated using linear isomorphism. After the scatterer displacement, Field II was used to simulate the speckle noise. Thus, it is possible to create a sequence of US images with realistic deformation. This technique was implemented in Matlab and is available for free download. The phantom deformation was validated by measuring the strain contrast from double-layered phantoms. Special attention was given to cardiovascular diseases due to their impact on Brazilian and world populations. During the last decades, the prevalence of cardiovascular pathologies has increased progressively, and has become a serious public health problem. They are among the major causes of death, hospitalizations and health expenses. In interventionist practice, intravascular ultrasound (IVUS) is used to obtain information about blood vessels and eventual pathologies. Therefore, we also created numeric IVUS phantoms. The simulation of the blood vessel was also based in finite elements method with linear isomorphism. However, a reliable IVUS simulation must consider the catheter path inside the blood vessel, because it determines the position of the transducer. Hence, we developed a new method, based on equilibrium of forces, to determine the minimum energy position of the catheter. The method was validated by comparing its position with the position of a real stainless steel IVUS guidewire and presented root mean squared error and Hausdorff mean smaller than 1 mm for both. We used two different techniques to track and estimate deformation of different structures in the simulated US images, namely, Optical Flow and 2D Block Matching. We applied an innovative implementation of 2D block matching with sub-pixel linear interpolation and displacement propagation. Then, the estimated deformation from both methods were compared with the numeric gold-standard, and 2D block matching presented better results than optical flow. After the work with numeric phantoms, real US equipment was utilized to acquire B-mode images from a physical phantom. Then, we performed the movement estimation of the imaged tissue to analyze its morphological and dynamic properties. The results were compared to the elastography images provided by the US equipment. In accordance with the results from the numeric simulation, 2D block matching presented better results than Optical flow. Finally, we performed the two speckle tracking on a set of numerically simulated IVUS images, where the images were divided into two sets of frames. The first set, S1, contained all the frames from the IVUS sequence and the second set, S2, contained only the frames corresponding to a specific phase of the cardiac cycle. Thus, we analyzed the trade-off between the impact of the cardiac motion and low frame rate. For the points located at the edges of the object, optical flow had a good performance for both S1 and S2. In homogenous regions, however, optical flow was able to track the points only in S2, suggesting that it is better to work with low frame rate and reduced cardiac motion, as in EKG-triggered IVUS acquisition. 2D block matching presented poor results in all points of both S1 and S2. Besides the simulation of ultrasound acquisition with deformation and structure tracking, in this work, we also developed a new filtering technique that is able to remove the speckle texture without blurring the edges. The proposed filter presented the best results when compared to other nine filters from the literature. We also developed a metric that uses the speckle texture of the image to provide a parameter that may help the user decide the size of the window of the filter.

Cette thèse concerne le développement d'un cadre de contrôle robotique pour l'élastographie ultrasonore quantitative. L'élastographie ultrasonore est une technique qui dévoile les paramètres élastiques du tissu qui sont généralement liés à une pathologie. Cette thèse propose trois nouvelles approches robotiques différentes pour pour assister la procédure d'élastographie. La première approche concerne le contrôle d'un robot actionnant une sonde à ultrasons pour effectuer un mouvement de palpation nécessaire pour l'élastographie par ultrasons. L'élasticité du tissu est utilisée pour concevoir une loi d'asservissement afin de maintenir un tissu d'intérêt rigide dans le champ de vision de la sonde ultrasonore. De plus, l'orientation de la sonde est contrôlée par un utilisateur humain pour explorer différentes vues du tissu pendant que l'élastographie est effectuée. La seconde approche exploite le recalage d'images déformables avec des images ultrasonores pour estimer l'élasticité tissulaire et aider à la compensation automatique par asservissement visuel ultrasonore d'un mouvement introduit dans le tissu. La troisième approche offre une méthodologie pour ressentir l'élasticité du tissu en déplaçant une sonde virtuelle dans l'image ultrasonore avec un dispositif haptique pendant que le robot effectue un mouvement de palpation. Les résultats expérimentaux des trois approches robotiques obtenus sur des fantômes constitués de tissus démontrent l'efficacité des méthodes proposées et ouvre des perspectives intéressantes pour l'élastographie ultrasonore assistée par robot. / This thesis concerns the development of a robotic control framework for quantitative ultrasound elastography. Ultrasound elastography is a technology that unveils elastic parameters of a tissue, which are commonly related with certain pathologies. This thesis proposes three novel robotic approaches to assist examiners with elastography. The first approach deals with the control of a robot actuating an ultrasound probe to perform palpation motion required for ultrasound elastography. The elasticity of the tissue is used to design a servo control law to keep a stiff tissue of interest in the field of view of the ultrasound probe. Additionally, the orientation of the probe is controlled by a human user to explore other tissue while elastography is performed. The second approach exploits deformable image registration of ultrasound images to estimate the tissue elasticity and to help in the automatic compensation by ultrasound visual servoing of a motion introduced into the tissue. The third approach offers a methodology to feel the elasticity of the tissue by moving a virtual probe in the ultrasound image with a haptic device while the robot is performing palpation motion. Experimental results of the three robotic approaches over phantoms with tissue-like offer an excellent perspective for robotic-assistance for ultrasound elastography.

Heart disease has remained the deadliest disease in the United States for the past 100 years. Imaging methods are frequently employed in cardiology in order to help clinicians diagnose the specific type of heart disease and to guide treatment decisions. Ultrasound is the most frequently used imaging modality in cardiology because it is inexpensive, portable, easy to use, and extremely safe for patients. Using a variety of imaging processing techniques, deformations exhibited by the cardiac tissue during contraction can be imaged with ultrasound and used as an indicator of myocardial health. This dissertation will demonstrate the clinical implementation of two ultrasound-based strain estimation techniques developed in the Ultrasound and Elasticity Imaging Laboratory at Columbia University. Each of the two imaging methods will be tailored for clinical applications using techniques for optimal strain estimation derived from ultrasound and imaging processing theory. The motion estimation rate (MER) used for strain estimation is examined in the context of the theoretical Strain Filter and used to increase the precision of axial strain estimation. Diverging beam sequences are used to achieve full-view high MER imaging within a single heartbeat. At approximately 500 Hz, the expected elastographic signal-to-noise ratio (E(SNRe|ε)) of the axial strain becomes single-peaked, indicating an absence of “peak-hopping” errors which can severely corrupt strain estimation. In order to mediate the tradeoff in spatial resolution resulting from the use of diverging beams, coherent spatial compounding is used to increase the accuracy of the lateral strain estimation, resulting in a more physiologic strain profile. A sequence with 5 coherently compounded diverging waves is used at 500 Hz to improve the radial SNRe of the strain estimation compared to a single-source diverging sequence at 500 Hz. The first technique, Myocardial Elastography (ME), is used in conjunction with an intracardiac echocardiography (ICE) system to image the formation of thermal ablation lesions in vivo using a canine model (n=6). By comparing the systolic strain before and after the formation of a lesion, lesion maps are generated which allow for the visualization of the lesion in real-time during the procedure. A good correlation is found between the lesion maps and the actual lesion volume as measured using gross pathology (r2=0.86). The transmurality of the lesions are also shown to be in good agreement with gross pathology. Finally, the feasibility of imaging gaps between neighboring lesions is established. Lesion size and the presence of gaps have been associated with the success rate of cardiac ablation procedures, demonstrating the value of ME as a potentially useful technique for clinicians to help improve patient outcomes following ablation procedures. The second technique, Electromechanical Wave Imaging (EWI), is implemented using a transthoracic echocardiography system in a study of heart failure patients (n=16) and healthy subjects (n=4). EWI uses the transient inter-frame strains to generate maps of electromechanical activation, which are then used to distinguish heart failure patients from healthy controls (p<.05). EWI was also shown to be capable of distinguishing responders from non-responders to cardiac resynchronization therapy (CRT) on the basis of the activation time of the lateral wall. These results indicate that EWI could be used as an adjunct tool to monitor patient response to CRT, in addition to helping guide lead placement prior to device implantation.

Ultrassonografia (US) é usada por médicos para ajudar em diagnósticos e intervenções. Ela fornece uma visada tomográfica de órgãos internos como, por exemplo, pâncreas aorta, fígado, bexiga, rins e baço. O médico pode utilizar a US para realizar apenas uma avaliação visual ou pode também comprimir o tecido para analisar a dinâmica, uma vez que a elasticidade da lesão pode estar relacionada à patologias. Consequentemente, diversos procedimentos computacionais vem sendo desenvolvidos com o intuito de fornecer ao médico informações acerca das propriedades elásticas do tecido. Entretanto, uma avaliação completa e objetiva dos procedimentos computacionais sobre US pode ser dificultada pelo difícil acesso a imagens com as propriedades desejadas ou pela falta de padrão-ouro para ser utilizado como referência. Portanto, nós desenvolvemos uma ferramenta capaz de criar phantoms numérico que imitam a compressão induzida por um médico através de um transdutor. A deformação do tecido é baseada em método doe elementos finitos e o deslocamento dos espalhadores é calculado usando isomorfismo linear. Depois do deslocamento dos espalhadores, Field II foi utilizado para simular o ruído Speckle. Assim, foi possível a criação de uma sequência de imagens de US com deformação realística. Este método foi implementado em Matlab e está disponível para download sem custos. A deformação do phantom foi validada através da medição de contraste de compressão em phantoms de duas camadas. Uma atenção especial foi dada a doenças cardiovasculares devido ao impacto que essas patologias causam no cenário médico do Brasil e do mundo. Nas últimas décadas, a prevalência de patologias cardiovasculares têm crescido progressivamente e se tornou uma séria questão de saúde pública. Elas estão entre as maiores causas de mortes, internações e gastos com saúde. Na prática intervencionista, o ultrassom intravascular (IVUS) é utilizado para obter informações do vaso sanguíneo e de eventuais patologias. Portanto, foi desenvolvida também uma simulação numérica de phantoms de IVUS. A simulação do vaso sanguíneo também se baseou em método dos elementos finitos e isomorfismo linear. Contudo, uma simulação confiável de IVUS deve considerar o caminho do cateter no interior do vaso sanguíneo, porque isto determina a posição do transdutor. Portanto, nós desenvolvemos um novo método, baseado em equilíbrio de forças, para determinar a posição de menor energia do cateter. O método foi validado através da comparação da posição estimada com a posição de um fio-guia de aço real e apresentou erro quadrático médio e média Hausdorff menor que 1 mm para ambos. Foram utilizados dois métodos diferentes para rastrear e estimar a deformação de determinadas estruturas no tecido: Optical Flow e 2D Block Matching. Foi aplicado uma implementação inovadora de 2D Block Matching com interpolação sub-pixel linear e propagação de deslocamento. Posteriormente, a validação será feita comparando-se a o movimento estimado com o padrão-ouro numérico utilizado para construir a simulação. O 2D block matching forneceu resultados melhores que o optical flow. Após a análise em phantoms numéricos, equipamento real de ultrassom foi utilizado para aquisição de imagens modo-B de phantoms físicos. Então, nós realizamos a estimativa do movimento das estruturas para analisar as propriedades morfológicas e dinâmicas do tecidos. Os resultados obtidos foram comparados com a elastografia fornecida pelo equipamento. Em acordo com os resultados obtidos na simulação numérica, o 2D block matching novamente apresentou resultados melhores que o optical flow. Finalmente, os dois métodos de rastreamento foi aplicada em imagens simuladas de IVUS, que foram divididas em 2 conjuntos de quadros. O primeiro conjunto, S1, continha todos os quadros da sequência de IVUS e o segundo conjunto, S2, continha apenas os quadros correspondentes a uma fase específica do ciclo cardíaco. Sendo assim, foi analisado o balanço entre o impacto do movimento cardíaco e a taxa de quadros. Para os pontos localizados nas bordas dos objetos, Optical flow teve um bom desempenho para ambos S1 e S2. Em regiões homogêneas, entretanto, o optical flow foi capaz de rastrear os pontos em S2, sugerindo que é melhor o trabalho com movimento cardíaco reduzido em detrimento da taxa de quadros, tal qual a aquisição de IVUS engatilhado por ECG. Já o 2D block matching apresentou um mau rastreamento para todos os pontos selecionados. Além da simulação da aquisição de ultrassonografia com deformação e do rastreamento de estruturas, também desenvolvemos uma nova técnica de filtragem capaz de remover a textura speckle sem borrar as bordas. A técnica proposta apresentou os melhores resultados quando comparados com outros nove filtros da literatura. Foi desenvolvida também uma nova métrica que utiliza o ruído speckle da própria imagem para fornecer um parâmetro que pode ajudar o usuário a decidir o tamanho da janelo de um filtro. / Ultrasonography (US) is used by physicians to help on diagnosis and interventions. It provides tomographic views of inner organs such as pancreas, aorta, inferior vena cava, liver, gall bladder, bile ducts, kidneys and spleen. The physician may utilize US to perform only a visual assessment or may also compress the tissue to analyze its dynamics, since lesion elasticity may be related to dangerousness. Consequently, several computational procedures have been developed in order to provide information about the elastic properties of the tissue. However, a thorough and objective evaluation of US computational procedures may be hindered by the difficult access to US images with the desired features and the lack of gold-standard parameters. Therefore, we developed a tool that is able to create numeric phantom that mimics the compression induced by physician with the transducer. The tissue deformation was based on finite elements method and the displacement of the scatterers were calculated using linear isomorphism. After the scatterer displacement, Field II was used to simulate the speckle noise. Thus, it is possible to create a sequence of US images with realistic deformation. This technique was implemented in Matlab and is available for free download. The phantom deformation was validated by measuring the strain contrast from double-layered phantoms. Special attention was given to cardiovascular diseases due to their impact on Brazilian and world populations. During the last decades, the prevalence of cardiovascular pathologies has increased progressively, and has become a serious public health problem. They are among the major causes of death, hospitalizations and health expenses. In interventionist practice, intravascular ultrasound (IVUS) is used to obtain information about blood vessels and eventual pathologies. Therefore, we also created numeric IVUS phantoms. The simulation of the blood vessel was also based in finite elements method with linear isomorphism. However, a reliable IVUS simulation must consider the catheter path inside the blood vessel, because it determines the position of the transducer. Hence, we developed a new method, based on equilibrium of forces, to determine the minimum energy position of the catheter. The method was validated by comparing its position with the position of a real stainless steel IVUS guidewire and presented root mean squared error and Hausdorff mean smaller than 1 mm for both. We used two different techniques to track and estimate deformation of different structures in the simulated US images, namely, Optical Flow and 2D Block Matching. We applied an innovative implementation of 2D block matching with sub-pixel linear interpolation and displacement propagation. Then, the estimated deformation from both methods were compared with the numeric gold-standard, and 2D block matching presented better results than optical flow. After the work with numeric phantoms, real US equipment was utilized to acquire B-mode images from a physical phantom. Then, we performed the movement estimation of the imaged tissue to analyze its morphological and dynamic properties. The results were compared to the elastography images provided by the US equipment. In accordance with the results from the numeric simulation, 2D block matching presented better results than Optical flow. Finally, we performed the two speckle tracking on a set of numerically simulated IVUS images, where the images were divided into two sets of frames. The first set, S1, contained all the frames from the IVUS sequence and the second set, S2, contained only the frames corresponding to a specific phase of the cardiac cycle. Thus, we analyzed the trade-off between the impact of the cardiac motion and low frame rate. For the points located at the edges of the object, optical flow had a good performance for both S1 and S2. In homogenous regions, however, optical flow was able to track the points only in S2, suggesting that it is better to work with low frame rate and reduced cardiac motion, as in EKG-triggered IVUS acquisition. 2D block matching presented poor results in all points of both S1 and S2. Besides the simulation of ultrasound acquisition with deformation and structure tracking, in this work, we also developed a new filtering technique that is able to remove the speckle texture without blurring the edges. The proposed filter presented the best results when compared to other nine filters from the literature. We also developed a metric that uses the speckle texture of the image to provide a parameter that may help the user decide the size of the window of the filter.

L'interaction onde-matière a toujours été un sujet d'étude en Physique, c’est le cas de la propagation des ondes élastiques dans le corps humain qu’a conduit à plusieurs modalités d'imagerie. En particulier, les techniques d'elastographie reposent sur l'utilisation des ondes de cisaillement pour obtenir une image élastique des tissus mous. Dans ce contexte, cette thèse présente une étude des différentes techniques d'élastographie, en prêtant particulier attention aux aspects plus fondamentaux comme à ces potentielles applications.Tout d'abord, cette thèse montre que l'élastographie impulsionnelle unidimensionnelle (1D) peut être utilisée pour évaluer l'élasticité des couches de tissue d'épaisseur inférieure à la longueur d'onde utilisée. A cet effet, des simulations et des expériences ont été réalisées avec différents fantômes formés par une couche mince immergée dans un milieu d'élasticité différente. La concordance entre expériences et simulations, ainsi que le valeur de l'élasticité obtenue par élastographie 1D et le valeur de l'élasticité intrinsèque de la couche permettent de valider cette technique. Au même temps ces résultats ont été comparés avec ceux obtenus par la technique de Supersonic Shear Imaging (SSI), où l'onde est guidée le long de la plaque. On ajustant la courbe de dispersion expérimentale obtenue par SSI avec un modèle de Lamb, l'élasticité intrinsèque de chaque plaque est estimée. Les résultats obtenus par élastographie 1D et SSI montrent un bon accord entre eux. Le principal avantage de l'élastographie 1D est qu’il n'est pas nécessaire d'utiliser un modèle pour estimer l'élasticité de la plaque. Deuxièmement, deux nouvelles modalités d'imagerie quantitative pour l'extraction de élasticité des tissus mou à partir d'un champ élastique complexe sont approfondies: l'Elastographie par Retournement Temporel et le filtre inverse passif. Le but de ces deux techniques est d'estimer localement l'élasticité des tissus, par la mesure de la taille de la tâche focale dans une expérience virtuelle de retournement temporel avec des ondes de cisaillement. A partir de l'étude du processus de retournement temporel dans les solides mous, la faisabilité de ces deux techniques est démontrée in vitro dans des échantillons "bi-couche" et in vivo dans le foie et les muscles, en utilisant le bruit physiologique naturel crée par l'activité cardiaque et musculaire. L'efficacité de l'élastographie par retournement temporel diminue dans le cas d'un champ diffus non isotrope. L'emploie du filtre inverse adaptée à une configuration de source de bruit, permet de rétablir l'isotropie du champ et d'améliorer la résolution pour la détection de petites inclusions. Le filtre inverse passif permet, de surcroît, de contrôler la fréquence qui domine le champ de retournement temporel. Ceci est exploité, dans la dernière partie du manuscrit, pour mener la première expérience de spectroscopie passive en volume. Deux situations sont envisagées: la dispersion due à la propagation d'ondes guidées dans des plaques minces et la dispersion des ondes due à la viscosité. / The interaction between wave and matter has long been studied in Physics. In particular, regarding medical applications, wave propagation through the human body resulted in several imaging modalities, each of which uses a specific type of wave linked to a given physical property. The elasticity of soft biological tissues is directly linked to its shear wave speed. Thus, in Elastography, shear waves are tracked for non-invasive assessment of the mechanical properties of soft tissues. In this context, this thesis proposes a study of different elastography techniques from a basic point of view, as well as from its potential applications. Firstly, in this manuscript, the use of 1D transient elastography for the quantitative elasticity assessment of thin layered soft tissues is proposed. Experiments on three phantoms with different elasticities and plate thicknesses were performed. Experimental shear wave speed estimations inside the plate were obtained and validated with finite difference simulation. In addition, the Supersonic Shear Imaging (SSI) technique was performed. For the SSI technique, the propagating wave inside the plate is guided as a Lamb wave. Experimental SSI dispersion curves were fitted using a generalized Lamb model to retrieve the plate bulk shear wave speed. Finally both techniques resulted in similar shear wave speed estimations. The main advantage of 1D transient elastography is that the bulk shear wave speed can be directly retrieved from a time of flight measurement without requiring a dispersion model. Secondly, throughout this thesis, two novel quantitative imaging modalities for extracting the soft tissue's elasticity from a complex reverberated diffuse elastic field are deepen: Time Reversal Elastography (TRE) and the passive inverse filter. The goal of both techniques is to locally estimate the tissue's elasticity, by measuring the focal spot size in a virtual time reversal experiment involving shear waves. By studying the Physics of a time reversal process in soft solids, the feasibility of both techniques as a quantitative imaging techniques is demonstrated in vitro in bi-layer phantoms and in vivo in the liver-belly muscle, by using the physiological noise due to heartbeats and muscular activity. The efficiency of TRE decreases in the presence of a non-isotropic diffuse field. The use of the inverse filter adapted to a passive source configuration, restores the isotropy of the field. As a consequence, the resolution of the elasticity images is improved, leading to a better detection of small inclusions. In addition, the passive inverse filter allows to control the frequency dominating the time reversed field. This is exploited in the last part of the manuscript to conduct the first passive wave spectroscopy experiment in the volume of a soft solid. Two situations are considered: dispersion due to guided wave propagation in thin plates and wave dispersion due to viscosity effects.

L’élastographie par ondes de cisaillement consiste essentiellement en deux étapes: d'abord, une onde de cisaillement est générée en appliquant soigneusement une source contrôlée externe (par exemple actionneur mécanique ou force de rayonnement ultrasonore); Alors les déplacements induits sont imagés et l'élasticité tissulaire est déduite de la propagation d'onde de cisaillement mesurée. Cependant, avec les techniques d'élastographie actuellement disponibles, l'estimation quantitative correcte de la viscosité n'est pas possible. Dans ce contexte, le but principal de cette thèse est double: d'abord, développer un outil capable d'estimer simultanément les propriétés viscoélastiques d'un solide souple, notamment en utilisant l'imagerie par cisaillement supersonique, puis de l'appliquer aux certains problèmes rencontrés en médecine et l'industrie alimentaire.La première étape consiste à utiliser la technique SSI pour générer des cartes de vitesses des ondes de cisaillement dans des milieux solides mous et isotropes. Dans ce contexte, cette technique a été utilisée pour évaluer le processus de coagulation du lait. Au cours de cette étape, les limites de la technique SSI pour obtenir une caractérisation rhéologique complète des solides viscoélastiques sont mis en évidence. Pour parvenir à cette caractérisation, la vitesse de propagation ondes de cisaillement et la absorption que l’onde subi en traversant le milieu doivent être évalués à la fois. Compte tenu des caractéristiques de la technique SSI, en raison des effets de diffraction due à la taille finie des sources, l’absorption ne peut pas être obtenue correctement de façon quantitative.La partie centrale de la thèse porte sur l’étude des avantages et des ses limites de la correction des effets de diffraction de la technique SSI à partir d’une approximation cylindrique. Cette étude a été réalisée expérimentalement en comparant les résultats obtenus avec ceux des simulations numériques. L’étude a montré que la correction cylindrique est utile pour estimer l'atténuation provoquée par l'absorption dans certaines conditions. Une fois déterminé la zone de validité de la procédure de correction, des cartes des vitesses et des cartes d'atténuation ont était obtenus. Ces cartes ont permis t la caractérisation rhéologique complète des milieux étudiés.Une fois validé cette correction nous avons procédé à réaliser trois applications d'intérêt pour obtenir les propriétés rhéologiques, une pour l’ industrie alimentaire et deux pour la médecine clinique : a) suivie et étude du processus de coagulation du lait b) suivie et étude de processus de la coagulation du sang in vitro, c) des expériences de caractérisation rhéologique du foie in vivo. Finalement, une étude de la correction cylindrique mis en œuvre a été utilisée pour caractériser rhéologiquement des solides mous avec isotropie transversale. Milieux avec différents degrés d'anisotropie ont été analysés à l'aide de simulations numériques. Les résultats obtenus montrent que pour de faibles niveaux d’anisotropie la correction cylindrique s’avère utile avec une erreur raisonnable. Pour des degrés plus élevés d'anisotropie la correction cylindrique conduit à des erreurs majeures dans l'estimation de l'atténuation. Des mesures des coefficients d’absorption ont été réalisées dans des phantoms de gel anisotropes et dans des échantillons de viande de bœuf avec des tissues musculaire / Shear wave elastography consists essentially of two steps: first, a shear wave is generated by an external controlled source (eg mechanical actuator or ultrasonic radiation force); then the induced displacements are imaged and the tissue elasticity is deduced from the measured shear wave propagation. However, with the currently available elastographic techniques, a quantitative estimation of viscosity is not possible. In this context, the objective of this thesis is twofold: first, to develop a tool capable of estimating the viscoelastic properties of a soft solid, in particular by using supersonic shear imaging (SSI), and then to apply it to some problems encountered in medicine and the food industry.The first stage consisted in using the SSI technique to generate shear wave velocity maps in soft, isotropic solid media. In this context, this technique was used to evaluate the milk coagulation process. During this stage, limitations of the SSI technique to obtain a complete rheological characterization of viscoelastic solids were demonstrated. To achieve this characterization, the velocity of the shear waves and the absorption generated when passing through the medium must be evaluated at the same time. Given the characteristics of the SSI technique, the absorption cannot be directly quantified due to diffraction.The central part of the thesis focuses in the study of the advantages and limitations of using a cylindrical approximation to correct the diffraction effects. This study was carried out experimentally and through numerical simulations. The study showed that cylindrical correction is useful for estimating the attenuation caused by absorption under certain conditions. After determining the validity zone of the correction, velocity and attenuation maps were obtained. These maps allowed the complete rheological characterization of the studied media.Once the correction was validated, three applications of interest were carried out to obtain rheological properties, one for the food industry and two for clinical medicine: a) monitoring the process of milk coagulation through storage and loss moduli maps b) following in vitro blood coagulation processes, c) rheological characterization experiments of the liver in vivo. Finally, the application of the cylindrical correction to characterize transversely isotropic soft solids was studied. Media with different degrees of anisotropy were analyzed through numerical simulations. The results obtained showed that for low levels of anisotropy the cylindrical correction proves useful within a reasonable error. For higher degrees of anisotropy the cylindrical correction leads to major errors in the estimation of the attenuation. Measurements of the absorption coefficients were performed in anisotropic gel phantoms and in beef samples with muscle tissue

Introduction: Chronic hepatitis B (CHB) is a viral infection that can lead to development of fibrosis and hepatocellular carcinoma (HCC). Several factors affecting disease progression have been reported, such as sex and region of origin. Liver stiffness and fibrosis can be evaluated using transient elastography. The degree of fibrosis is an important parameter when deciding if treatment and HCC surveillance is indicated. Aim1) To compare patients with CHB according to sex and region of origin regarding the parameters liver stiffness, presence of significant fibrosis, hepatitis B e antigen (HBeAg) positivity, frequency of elevated alanine aminotransferase (ALT) levels and HCC surveillance.2) To identify factors associated with significant liver fibrosis. Methods: 410 patients with a registered doctor’s visit 2015–2018 at the Department of Infectious Diseases at Örebro University Hospital were included. A systematic review of medical records was performed and groups (women-men, regions of origin) were compared. Multivariate logistic regression was used to identify factors associated with significant fibrosis. Results: Men had significantly higher liver stiffness values, higher presence of significant fibrosis, and were more frequently under HCC surveillance compared to women. No other significant differences were found regarding the studied parameters, neither related to sex, nor to region of origin. Factors associated with significant fibrosis were: male sex, elevated ALT levels and hepatitis D virus (HDV) co-infection. Conclusions: Men had a higher frequency of significant fibrosis compared to women. Factors associated with significant fibrosis were male sex, elevated ALT values and HDV co-infection.

Le but de cette thèse était d’apporter un certain nombre d’améliorations techniques et méthodologiques à l’élastographie par résonance magnétique afin d’assurer le confort du patient, mais aussi de mieux comprendre les phénomènes impliqués dans le changement des propriétés mécaniques du foie. Ainsi, cette thèse a été construite de manière à améliorer les méthodes et les valider sur modèles animaux. La faisabilité clinique était étudiée en parallèle. Cette thèse repose principalement sur deux études expérimentales. En effet, différents modèles animaux ont été utilisés afin de mettre en relief le rôle de l’élastographie par résonance magnétique dans le diagnostic des maladies chroniques du foie. Ce doctorat a débouché sur deux publications en premier auteur. La première valide la méthode sur foie entier chez des rats avec fibrose hépatique induite au tétrachlorure de carbone et montre que les paramètres visco-élastiques sont corrélés à la quantité de fibrose. La deuxième étude, plus complexe, intègre différents modèles animaux afin d’apporter un début de réponse au rôle de l’élastographie par IRM dans le diagnostic des maladies à foie stéatosique. Il s’agissait de rats nourris avec une diète standard, une diète déficiente en choline jusqu’à 8 semaines pour induire une stéatohépatite, une diète enrichie en acide orotique pendant 2 semaines pour induire une stéatose simple, ou de rats ayant reçu une injection unique de CCl4 pour provoquer une lésion hépatique aigue. Les résultats principaux montraient une augmentation de la viscosité chez les rats à stéatose simple et une augmentation à la fois de l’élasticité et de la viscosité chez les rats avec lésion hépatique aigue. De plus, il a été montré chez les rats avec stéatohépatite une augmentation de l’élasticité et de la viscosité en l’absence de fibrose établie, alors que l’activation de la fibrogenèse était enclenchée, accompagnée d’une légère inflammation. L’analyse multivariée de tous les rats a montré que les changements d’élasticité sont principalement expliqués par l’activation des cellules stellaires (et donc de la fibrogenèse), alors que les changements de viscosité pourraient être expliqués par la présence de graisse. Ainsi, cette thèse a permis d’améliorer le confort du patient (matelas d’IRM et séquence rapide) pour faciliter l’intégration de cet examen en routine clinique, mais également de valider l’élastographie comme marqueur de la fibrose et des propriétés mécaniques des tissus. Pour finir, cette thèse a mis en avant le rôle potentiel de l’élastographie par IRM pour la détection précoce des patients à risque dans le cadre des stéatohépatites.

Magnetic Resonance Elastography (MRE) is a medical imaging technique used to generate a map of tissue elasticity. The resulting image is known as an elastogram, and gives a quantitative measure of stiffness in the examined tissue. The method is indirect; the elasticity, itself, is not measured. Instead, the physical response to a known stress is captured using magnetic resonance imaging, and is related to an elasticity parameter through a mathematical model of the tissue. In dynamic elastography, a harmonic stress is externally applied by a mechanical actuator, which is oriented to induce shear waves through the tissue. Once the system reaches a quasi-steady state, the displacement field is measured at a sequence of points in time. This data is the input to elasticity reconstruction algorithms. In this dissertation, the tissue is modelled as a linearly viscoelastic, isotropic continuum, undergoing harmonic motion with a known fundamental frequency. With this model, viscoelasticity is described by the complex versions of Lamé's first and second parameters. The second parameter, known as the complex shear modulus, is the one of interest. The term involving the first parameter is usually deemed negligible, so is ignored. The task is to invert the tissue model, a system of linear differential equations, to find the desired parameter. Direct inversion methods use the measured data directly in the model. Most current direct methods assume the shear modulus can be approximated locally by a constant, so ignore all derivative terms. This is known as the local homogeneity assumption, and allows for a simple, algebraic solution. The accuracy, however, is limited by the validity of the assumption. One of the purposes of MRE is to find pathological tissue marked by a higher than normal stiffness. At the boundaries of such diseased tissue, the stiffness is expected to change, invalidating the local homogeneity assumption, and hence, the shear modulus estimate. In order to capture the true shape of any stiff regions, a method must allow for local variations. Two new inversion methods are derived. In the first, a Green's function is introduced in an attempt to solve the differential equations. To simplify the system, the tissue is taken to be incompressible, another common assumption in direct inversion methods. Unfortunately, without designing an iterative procedure, the method still requires a homogeneity assumption, limiting potential accuracy. However, it is very fast and robust. In the second new inversion method, neither of the local homogeneity or incompressibility assumptions are made. Instead, the problem is re-posed in a quadratic optimization form. The system of linear differential equations is set as a constraint, and any free parameters are steered through quadratic programming techniques. It is found that, in most cases, there are no degrees of freedom in the optimization problem. This suggests that the system of differential equations has a fully determined solution, even without initial, boundary, or regularization conditions. The result is that estimates of the shear modulus and its derivatives can be obtained, locally, without requiring any assumptions that might invalidate the solution. The new inversion algorithms are compared to a few prominent, existing ones, testing accuracy and robustness. The Green's function method is found to have a comparable accuracy and noise performance to existing techniques. The second inversion method, employing quadratic optimization, is shown to be significantly more accurate, but not as robust. It seems the two goals of increasing accuracy and robustness are somewhat conflicting. One possible way to improve performance is to gather and use more data. If a second displacement field is generated using a different actuator location, further differential equations are obtained, resulting in a larger system. This enlarged system is better determined, and has improved signal-to-noise properties. It is shown that using data from a second field can increase accuracy for all methods.

Magnetic Resonance Elastography (MRE) is a medical imaging technique used to generate a map of tissue elasticity. The resulting image is known as an elastogram, and gives a quantitative measure of stiffness in the examined tissue. The method is indirect; the elasticity, itself, is not measured. Instead, the physical response to a known stress is captured using magnetic resonance imaging, and is related to an elasticity parameter through a mathematical model of the tissue. In dynamic elastography, a harmonic stress is externally applied by a mechanical actuator, which is oriented to induce shear waves through the tissue. Once the system reaches a quasi-steady state, the displacement field is measured at a sequence of points in time. This data is the input to elasticity reconstruction algorithms. In this dissertation, the tissue is modelled as a linearly viscoelastic, isotropic continuum, undergoing harmonic motion with a known fundamental frequency. With this model, viscoelasticity is described by the complex versions of Lamé's first and second parameters. The second parameter, known as the complex shear modulus, is the one of interest. The term involving the first parameter is usually deemed negligible, so is ignored. The task is to invert the tissue model, a system of linear differential equations, to find the desired parameter. Direct inversion methods use the measured data directly in the model. Most current direct methods assume the shear modulus can be approximated locally by a constant, so ignore all derivative terms. This is known as the local homogeneity assumption, and allows for a simple, algebraic solution. The accuracy, however, is limited by the validity of the assumption. One of the purposes of MRE is to find pathological tissue marked by a higher than normal stiffness. At the boundaries of such diseased tissue, the stiffness is expected to change, invalidating the local homogeneity assumption, and hence, the shear modulus estimate. In order to capture the true shape of any stiff regions, a method must allow for local variations. Two new inversion methods are derived. In the first, a Green's function is introduced in an attempt to solve the differential equations. To simplify the system, the tissue is taken to be incompressible, another common assumption in direct inversion methods. Unfortunately, without designing an iterative procedure, the method still requires a homogeneity assumption, limiting potential accuracy. However, it is very fast and robust. In the second new inversion method, neither of the local homogeneity or incompressibility assumptions are made. Instead, the problem is re-posed in a quadratic optimization form. The system of linear differential equations is set as a constraint, and any free parameters are steered through quadratic programming techniques. It is found that, in most cases, there are no degrees of freedom in the optimization problem. This suggests that the system of differential equations has a fully determined solution, even without initial, boundary, or regularization conditions. The result is that estimates of the shear modulus and its derivatives can be obtained, locally, without requiring any assumptions that might invalidate the solution. The new inversion algorithms are compared to a few prominent, existing ones, testing accuracy and robustness. The Green's function method is found to have a comparable accuracy and noise performance to existing techniques. The second inversion method, employing quadratic optimization, is shown to be significantly more accurate, but not as robust. It seems the two goals of increasing accuracy and robustness are somewhat conflicting. One possible way to improve performance is to gather and use more data. If a second displacement field is generated using a different actuator location, further differential equations are obtained, resulting in a larger system. This enlarged system is better determined, and has improved signal-to-noise properties. It is shown that using data from a second field can increase accuracy for all methods.