We consider the design of finite element methods for inverse problems with full-field data governed by elliptic forward operators. Such problems arise in applications in inverse heat conduction, in mechanical property characterization, and in medical imaging. For this class of problems, novel finite element methods have been proposed (Barbone et al., 2010) that give good performance, provided the solutions are in the H^1(Ω) function space. The material property distributions being estimated can be discontinuous, however, and therefore it is desirable to have formulations that can accommodate discontinuities in both data and solution. Toward this end, we present a mixed variational formulation for this class of problems that handles discontinuities well. We motivate the mixed formulation by examining the possibility of discretizing using a discontinuous discretization in an irreducible finite element method, and discuss the limitations of that approach. We then derive a new mixed formulation based on a least-square error in the constitutive equation. We prove that the continuous variational formulations are well-posed for applications in both inverse heat conduction and plane stress elasticity. We derive a priori error bounds for discretization error, valid in the limit of mesh refinement. We demonstrate convergence of the method with mesh refinement in cases with both continuous and discontinuous solutions. Finally we apply the formulation to measured data to estimate the elastic shear modulus distributions in both tissue mimicking phantoms and in breast masses from data collected in vivo.

Il est maintenant admis que la composition de la plaque athérosclérotique est un déterminant majeur de sa vulnérabilité à se rompre. Vu que la composition de la plaque affecte ses propriétés mécaniques, l'évaluation locale des propriétés mécaniques de la plaque d'athérome peut nous informer sur sa vulnérabilité. L'objectif est de comparer les techniques d’élastographie ultrasonores endovasculaire (EVE) et non-invasive (NIVE) en fonction de leur potentiel à identifier les composantes calcifiées et lipidiques de la plaque. Les acquisitions intravasculaire et extravasculaire ont été effectuées sur les artères carotidiennes de neuf porcs hypercholestérolémiques à l’aide d’un cathéter de 20 MHz et d'une sonde linéaire de 7.5 MHz, respectivement. Les valeurs de déformation radiale et axiale, rapportés par EVE et NIVE, ont été corrélées avec le pourcentage des zones histologiques calcifiées et lipidiques pour cinq plaques. Nos résultats démontrent une bonne corrélation positive entre les déformations et les composantes calcifiées (r2 = 0.82, P = 0.034 valeur par EVE et r2 = 0.80, P = 0.041 valeur par NIVE). Une forte corrélation entre les déformations axiales et les contenus lipidiques par NIVE (r2 = 0.92, P-value = 0.010) a été obtenue. En conclusion, NIVE et EVE sont des techniques potentielles pour identifier les composants de la plaque et aider les médecins à diagnostiquer précocement les plaques vulnérables. / It is now widely accepted that plaque composition is a major determinant of plaque’s vulnerability to rupture. Since composition of the plaque affects its mechanical properties, the local assessment of mechanical properties of atherosclerotic plaque may inform us about plaque’s vulnerability. The objective is to compare ultrasonic endovascular elastography (EVE) versus non-invasive vascular elastography (NIVE) according to their potential to identify plaque contents. Intravascular and extravascular acquisitions were performed on carotid arteries of nine hypercholesterolemic minipigs with a 20 MHz catheter and a 7.5 MHz standard probe, respectively. Radial and axial strain values, reported by EVE and NIVE respectively, were correlated with histological area of lipid and calcium for five plaques. Our results demonstrate a good positive correlation between strains and calcified contents (r2=0.82, P-value=0.034 by EVE and r2=0.80, P-value= 0.041 by NIVE). Additionally, there is a strong correlation between axial strains and lipid contents by NIVE (r2=0.92, P-value= 0.010). In conclusion, NIVE and EVE are the potential techniques to identify plaque components and to help physicians to early diagnose the vulnerable plaques.

Il est maintenant admis que la composition de la plaque athérosclérotique est un déterminant majeur de sa vulnérabilité à se rompre. Vu que la composition de la plaque affecte ses propriétés mécaniques, l'évaluation locale des propriétés mécaniques de la plaque d'athérome peut nous informer sur sa vulnérabilité. L'objectif est de comparer les techniques d’élastographie ultrasonores endovasculaire (EVE) et non-invasive (NIVE) en fonction de leur potentiel à identifier les composantes calcifiées et lipidiques de la plaque. Les acquisitions intravasculaire et extravasculaire ont été effectuées sur les artères carotidiennes de neuf porcs hypercholestérolémiques à l’aide d’un cathéter de 20 MHz et d'une sonde linéaire de 7.5 MHz, respectivement. Les valeurs de déformation radiale et axiale, rapportés par EVE et NIVE, ont été corrélées avec le pourcentage des zones histologiques calcifiées et lipidiques pour cinq plaques. Nos résultats démontrent une bonne corrélation positive entre les déformations et les composantes calcifiées (r2 = 0.82, P = 0.034 valeur par EVE et r2 = 0.80, P = 0.041 valeur par NIVE). Une forte corrélation entre les déformations axiales et les contenus lipidiques par NIVE (r2 = 0.92, P-value = 0.010) a été obtenue. En conclusion, NIVE et EVE sont des techniques potentielles pour identifier les composants de la plaque et aider les médecins à diagnostiquer précocement les plaques vulnérables. / It is now widely accepted that plaque composition is a major determinant of plaque’s vulnerability to rupture. Since composition of the plaque affects its mechanical properties, the local assessment of mechanical properties of atherosclerotic plaque may inform us about plaque’s vulnerability. The objective is to compare ultrasonic endovascular elastography (EVE) versus non-invasive vascular elastography (NIVE) according to their potential to identify plaque contents. Intravascular and extravascular acquisitions were performed on carotid arteries of nine hypercholesterolemic minipigs with a 20 MHz catheter and a 7.5 MHz standard probe, respectively. Radial and axial strain values, reported by EVE and NIVE respectively, were correlated with histological area of lipid and calcium for five plaques. Our results demonstrate a good positive correlation between strains and calcified contents (r2=0.82, P-value=0.034 by EVE and r2=0.80, P-value= 0.041 by NIVE). Additionally, there is a strong correlation between axial strains and lipid contents by NIVE (r2=0.92, P-value= 0.010). In conclusion, NIVE and EVE are the potential techniques to identify plaque components and to help physicians to early diagnose the vulnerable plaques.

Die vorliegende medizinische Dissertation untersucht nicht-invasive bildgebende Verfahren wie die konventionelle Sonographie, die Acoustic radiation force impulse (ARFI)-Elastographie sowie die Transiente Elastographie (TE) zur Detektion von Komplikationen in der Frühphase nach allogener Stammzelltransplantation. Dem kurativen Therapieansatz der Stammzelltransplantation steht ein hohes Komplikationspotential gegenüber. Besonders hepatobiliär treten Graft-versus-host Erkrankungen (GvHD) sowie Gefäßkomplikationen (VOD) auf. Der bisherige diagnostische Goldstandard, die Leberbiopsie, ist als invasives Verfahren mit einer hohen Intra- und Inter-Untersucher-Variabilität sowie der geringen Repräsentativität als Screeningmethode ungeeignet. Die Elastographieverfahren ARFI und TE als nicht-invasive Alternativen ermitteln die Lebergewebesteifigkeit als Surrogatparameter fibrotischer Veränderungen und wurden bereits in zahlreichen Studien als geeignete Diagnoseverfahren für Leberfibrose und -zirrhose unterschiedlicher Ätiologie definiert. Ziel dieser prospektiven Pilotstudie war die Evaluation der genannten Methoden zur Detektion von Frühkomplikationen nach allogener Stammzelltransplantation. Die Ergebnisse der Studie zeigen, dass sowohl die konventionelle Sonographie als auch die Transiente Elastographie pathologische Organveränderungen vor allem des hepatobiliären Systems detektieren können. Allerdings erscheinen diese Veränderungen unspezifisch. Es bestehen keine signifikanten Unterschiede zwischen Patienten mit und ohne Komplikationen. Anders bei der ARFI-Elastographie. Hier zeigten die Messwerte im linken Leberlappen signifikant höhere Werte bei Patienten mit Komplikationen. Zusammenfassend ist die ARFI-Elastographie zur Prädiktion möglicher Komplikationen nach allogener Stammzelltransplantation geeignet, sollte allerdings mit anderen diagnostischen Verfahren ergänzt werden.:III. Inhaltsverzeichnis I. Vorbemerkungen 2 II. Bibliographische Beschreibung 3 III. Inhaltsverzeichnis 4 IV. Abkürzungsverzeichnis 5 1. Einleitung 1.1. Hämatopoetische Stammzelltransplantation 6 2. Komplikationen nach allogener Stammzelltransplantation und deren Diagnostik 2.1. Akute Komplikationen 8 2.2. Akute und chronische Graft-versus-host Erkrankung 9 2.3. Hepatobiliäre Komplikationen 12 2.3.1. Veno-occlusive disease 12 2.3.2. Drug-induced liver injury 14 2.3.3. Problematik der Diagnostik 16 3. Risikostratifizierung bei Stammzelltransplantation 16 3.1. Karnovsky Index und Eastern Cooperative Oncology Group Index 16 3.2. Hematopoietic cell transplantation comorbidity index 17 3.3. Leberspezifisches Risikoassessment 18 4. Nicht-invasive Leberdiagnostik 19 4.1. Konventionelle Sonographie 19 4.2. Elastographie 20 4.2.1. Transiente Elastographie 21 4.2.2. Acoustic radiation force impulse imaging 22 5. Prospektive Studie: Sonographische Evaluation von Komplikationen in der Frühphase nach allogener Stammzelltransplantation 23 5.1. Methodik 24 5.2. Eigener Arbeitsanteil 24 6. Publikationsmanuskript 25 7. Zusammenfassung 32 8. Literaturverzeichnis 36 9. Selbständigkeitserklärung 44 10. Lebenslauf 45 11. Danksagung 46

To compare ultrasound-based acoustic structure quantification (ASQ) with established non-invasive techniques for grading and staging fatty liver disease.

Magnetic Resonance Elastography is a method of imaging the elasticity of soft tissues through measurement of small motions induced into a sample. It shows great promise in the detection of a wide variety of pathologies, especially tumours. An imaging protocol was developed to acquire MR elastography data for use in a clinical setting. A 3D gradient echo sequence was modified to allow for the detection of harmonic motion and tested on silicone phantoms and ex-vivo muscle and brain samples. The time for acquiring a high resolution, quantitative dataset of 3D motions was about 45 minutes. Our imaging method included motion encoding along all three coordinate axes and at several time points along the motion cycle. This time could be easily be reduced by more than half for future clinical use, while still retaining full quantitative data. A modified EPI sequence shows promise for even faster acquisition. The ability to detect the mechanical anisotropy of brain and muscle tissue in ex-vivo samples was also investigated. Initial results from the muscle data indicate a change in shear wavelength is observed for actuation along orthogonal axes. This is a strong indicator of anisotropy detection. Further work needs to be done to improve results from the brain sample as preliminary results are inconclusive.

INTRODUÇÃO: A cirrose é a oitava causa de mortalidade no mundo, e sua progressão e estadiamento são de extrema importância nos pacientes com doença terminal do fígado. A presença de cirrose é reconhecida como risco aumentado de carcinoma hepatocelular (CHC) e o seu aparecimento está diretamente relacionado ao grau de fibrose do fígado. Na última década, notou-se o desenvolvimento e aperfeiçoamento dos métodos de predição do grau de fibrose e cirrose, através de métodos não-invasivos, com o objetivo de substituir a biópsia hepática. A população em lista de espera para transplante de fígado apresenta graus diferentes de fibrose hepática, que pode não estar diretamente relacionada ao MELD. Além disso, esses pacientes apresentam CHC no momento da triagem para transplante de fígado. Não existe avaliação desta população por elastografia. OBJETIVO: O objetivo deste trabalho foi avaliar os pacientes em triagem para transplante de fígado, com e sem carcinoma hepatocelular, pela elastografia hepática com Fibroscan® e ARFI. MÉTODO: Foram estudados 103 pacientes adultos do ambulatório de triagem da Disciplina de Transplante de Órgãos do Aparelho Digestivo HC/FMUSP, no período de outubro de 2012 à dezembro de 2013. A amostragem foi por conveniência e foram avaliados dados clínicos, epidemiográficos, laboratoriais, imagem, elastográficos e o desfecho. Análise de elastografia transitória (ET) foi feita pelo Fibroscan® TM (Echosens, França) e força impulso por radiação acústica (ARFI) (Siemens Acuson S2000, Alemanha) nos grupos com e sem CHC comprovados de acordo com orientação de diagnóstico pelas diretrizes européias (EASL) e americanas (AASLD). Para a análise estatística foi realizado o teste de Mann-Whitney, teste não paramétrico aplicado para duas amostras independentes; o teste de Fisher e o método ANOVA através do teste de Kruskal-Wallis ou teste de Tukey para comparações múltiplas. Foi realizado também a curva ROC para avaliação dos testes diagnósticos e ponto de corte. O valor considerado de p significativo foi <0,05. RESULTADOS: Entre os pacientes avaliados, a maioria foi de homens (68%), com idade média de 53 ± 11,5 anos. A etiologia mais comum foi o vírus da hepatite C (VHC) em 34,9%. A classificação pelo escore Child-Turcotte-Pugh (CTP) mostrou: pacientes classe A em 38,4%, classe B em 47,2% e classe C em 14,2%. O valor do MELD médio dos pacientes foi de 14,75 (± 6,45) e a mediana de 14 (variando, 6 - 32). Na população estudada de 103 pacientes, a ET (Fibroscan®) foi realizada com sucesso em 75 de 103 pacientes e ARFI em 78 de 78 pacientes. A etiologia VHC e elevados valores de alfa-feto proteína foram fatores de risco para a presença de CHC. Os valores de MELD mais elevados foram significativos nos pacientes que evoluíram a óbito. A curva ROC mostrou respectivamente sensibilidade e especificidade para a AFP de 50% e 86% (valor de corte 9,1); ET (valor de corte 9 kPa) 92% e 17%; e ARFI 21% e 92% (valor de corte 2,56 m/s). O valor médio da ET nos pacientes com CHC foi de 30,4 ± 21,0 kPa, do ARFI do parênquima hepático foi de 1,97 ± 0,64 e ARFI do nódulo hepático foi de 1,89 ± 0,74. CONCLUSÃO: Os pacientes em triagem para transplante de fígado com carcinoma hepatocelular apresentam valores elevados de elastografia tanto pelo Fibroscan® quanto pelo ARFI®. A elastografia apresenta-se como uma importante ferramenta não invasiva para o acompanhamento de cirróticos graves podendo ajudar no manejo do carcinoma hepatocelular / INTRODUCTION: Cirrhosis is the eighth leading cause of mortality worldwide and its progression and staging are extremely important in patients with end liver disease. The presence of cirrhosis is recognized as an increased risk of hepatocellular carcinoma (HCC) and its incidence is directly related to the degree of liver fibrosis. In the last decade, was noted the development and improvement of methods for predicting the degree of fibrosis and cirrhosis using non-invasive methods, aiming to replace the liver biopsy. The population on the liver transplant waiting list presents different degrees of liver fibrosis, which may not be directly related to MELD. In addition, these patients have HCC at the time of screening for liver transplantation. There is no evaluation of this population by elastography. OBJECTIVE: The aim of this study was to evaluate patients on screened to the list for liver transplantation, with and without hepatocellular carcinoma, by liver elastography with Fibroscan and ARFI. METHOD: Were studied 103 adult patients from the screening for liver transplantation waiting list on the Liver and Gastrointestinal Transplant Division HC/FMUSP from October 2012 to December 2013. Sampling for convenience and evaluation clinical data, epidemiological, laboratory, imaging, elastography findings and outcome. Analysis of transient elastography (TE) by Fibroscan TM (Echosens, France) and Acoustic Radiation Force Impulse (ARFI) by (Siemens Acuson S2000, Germany) in patients with and without HCC proven in accordance with guidelines of diagnosis EASL/AASLD. Fisher\'s ANOVA or Kruskal-Wallis tests Whitney-Mann Test were performed. Tukey and define cut-of for examinations with ROC curves. The p value considered was < 0.05. RESULTS: Among the patients, the majority were men (68%), mean age 53 ± 11.5 years. This is the most common cause of hepatitis C virus (HCV) 34.9%. The classification by Child-Turcotte-Pugh score (CTP) showed: class A patients in 38.4%, 47.2% in class B and class C in 14.2%. The average value of MELD patients was 14.75 (± 6.45) and a median of 14 (range, 6-32). In the study population of 103 patients, the ET (Fibroscan) was successfully performed in 75 of 103 patients and ARFI in 78 of 78 patients. The HCV etiology and high levels of alpha-fetoprotein were risk factors for the presence of HCC. MELD values were significant higher in patients who died. The ROC curve shown respectively sensitivity and specificity for AFP of 50% and 86% (cutoff 9.1); ET (9 cutoff kPa) 92% to 17%; and ARFI 21% and 92% (cut-off 2.56 m / s). The average value of ET in HCC patients was 30.4 ± 21.0 kPa, the ARFI parenchymal liver was 1.97 ± 0.64 and ARFI liver nodules was 1.89 ± 0.74. CONCLUSION: Patients in screening for liver transplantation with hepatocellular carcinoma have elevated values of both elastography by Fibroscan as the ARFI®. Elastography is presented as an important non-invasive tool for monitoring severe cirrhosis may help in management of hepatocellular carcinoma

Este trabalho aborda o desenvolvimento de um aparato instrumental para efetuar medidas elastográficas por ultrassom. No qual foi considerado a elastografia tradicional que busca analisar as propriedades mecânicas de viscosidade e elasticidade de um meio, através da compressão e descompressão, de modo a simular o processo de palpação utilizado pelos médicos para avaliar a rigidez de um tecido, pois é sabido que estas mudanças estão relacionados a alguma forma de lesão do tecido biológico. Para alcançar tal propósito, foi construído simuladores de tecidos moles com características mecânicas próximas ao tecido biológico, nos quais foram utilizados materiais a base de parafinas (hidrocarbonetos) e gelatinas (proteínas extraída da hidrólise do colágeno de tecidos bovinos/suínos). Além do mais, foram introduzidos, na mistura, fluidos magnetoreológicos (FMR), que permitiram alterar estas propriedades mecânicas através da aplicação de um campo magnético externo. Os resultados apontam a viabilidade do protótipo em levantar o módulo de elasticidade destes simuladores, além de torná-lo um elemento diferencial para treinamento de profissionais da área de saúde e possível criação de protocolo para calibração de diferentes tumores e análise de medidas elastográficas, a partir da alteração de rigidez de um meio através da aplicação de campos magnéticos externos. / This work approaches the development of an apparatus to perform instrumental measures elastográficas ultrasound. In elastography which was traditionally considered that seeks to analyze the mechanical properties of viscosity and elasticity of a medium, through compression and decompression in order to simulate the palpation process used by physicians to evaluate stiffness of a fabric, it is known that these changes are related to some form of injury of biological tissue. To achieve this goal, was constructed simulators soft tissues mechanical characteristics close to biological tissue in which the materials were used based on paraffin (oil) and gelatin (protein hydrolysis of collagen extracted from bovine tissue / pigs). Besides, were introduced into the mixture, magnetorheological fluids (FMR) which allowed to change these mechanical properties by applying an external magnetic field. The results indicate the viability of the prototype in raising the modulus of elasticity of these simulators, and make it a differential element of training for health professionals and possible creation of protocol for calibration of different tumors and analysis of measures elastográficas from changing the stiffness of a medium by applying external magnetic fields.

INTRODUÇÃO: A cirrose é a oitava causa de mortalidade no mundo, e sua progressão e estadiamento são de extrema importância nos pacientes com doença terminal do fígado. A presença de cirrose é reconhecida como risco aumentado de carcinoma hepatocelular (CHC) e o seu aparecimento está diretamente relacionado ao grau de fibrose do fígado. Na última década, notou-se o desenvolvimento e aperfeiçoamento dos métodos de predição do grau de fibrose e cirrose, através de métodos não-invasivos, com o objetivo de substituir a biópsia hepática. A população em lista de espera para transplante de fígado apresenta graus diferentes de fibrose hepática, que pode não estar diretamente relacionada ao MELD. Além disso, esses pacientes apresentam CHC no momento da triagem para transplante de fígado. Não existe avaliação desta população por elastografia. OBJETIVO: O objetivo deste trabalho foi avaliar os pacientes em triagem para transplante de fígado, com e sem carcinoma hepatocelular, pela elastografia hepática com Fibroscan® e ARFI. MÉTODO: Foram estudados 103 pacientes adultos do ambulatório de triagem da Disciplina de Transplante de Órgãos do Aparelho Digestivo HC/FMUSP, no período de outubro de 2012 à dezembro de 2013. A amostragem foi por conveniência e foram avaliados dados clínicos, epidemiográficos, laboratoriais, imagem, elastográficos e o desfecho. Análise de elastografia transitória (ET) foi feita pelo Fibroscan® TM (Echosens, França) e força impulso por radiação acústica (ARFI) (Siemens Acuson S2000, Alemanha) nos grupos com e sem CHC comprovados de acordo com orientação de diagnóstico pelas diretrizes européias (EASL) e americanas (AASLD). Para a análise estatística foi realizado o teste de Mann-Whitney, teste não paramétrico aplicado para duas amostras independentes; o teste de Fisher e o método ANOVA através do teste de Kruskal-Wallis ou teste de Tukey para comparações múltiplas. Foi realizado também a curva ROC para avaliação dos testes diagnósticos e ponto de corte. O valor considerado de p significativo foi <0,05. RESULTADOS: Entre os pacientes avaliados, a maioria foi de homens (68%), com idade média de 53 ± 11,5 anos. A etiologia mais comum foi o vírus da hepatite C (VHC) em 34,9%. A classificação pelo escore Child-Turcotte-Pugh (CTP) mostrou: pacientes classe A em 38,4%, classe B em 47,2% e classe C em 14,2%. O valor do MELD médio dos pacientes foi de 14,75 (± 6,45) e a mediana de 14 (variando, 6 - 32). Na população estudada de 103 pacientes, a ET (Fibroscan®) foi realizada com sucesso em 75 de 103 pacientes e ARFI em 78 de 78 pacientes. A etiologia VHC e elevados valores de alfa-feto proteína foram fatores de risco para a presença de CHC. Os valores de MELD mais elevados foram significativos nos pacientes que evoluíram a óbito. A curva ROC mostrou respectivamente sensibilidade e especificidade para a AFP de 50% e 86% (valor de corte 9,1); ET (valor de corte 9 kPa) 92% e 17%; e ARFI 21% e 92% (valor de corte 2,56 m/s). O valor médio da ET nos pacientes com CHC foi de 30,4 ± 21,0 kPa, do ARFI do parênquima hepático foi de 1,97 ± 0,64 e ARFI do nódulo hepático foi de 1,89 ± 0,74. CONCLUSÃO: Os pacientes em triagem para transplante de fígado com carcinoma hepatocelular apresentam valores elevados de elastografia tanto pelo Fibroscan® quanto pelo ARFI®. A elastografia apresenta-se como uma importante ferramenta não invasiva para o acompanhamento de cirróticos graves podendo ajudar no manejo do carcinoma hepatocelular / INTRODUCTION: Cirrhosis is the eighth leading cause of mortality worldwide and its progression and staging are extremely important in patients with end liver disease. The presence of cirrhosis is recognized as an increased risk of hepatocellular carcinoma (HCC) and its incidence is directly related to the degree of liver fibrosis. In the last decade, was noted the development and improvement of methods for predicting the degree of fibrosis and cirrhosis using non-invasive methods, aiming to replace the liver biopsy. The population on the liver transplant waiting list presents different degrees of liver fibrosis, which may not be directly related to MELD. In addition, these patients have HCC at the time of screening for liver transplantation. There is no evaluation of this population by elastography. OBJECTIVE: The aim of this study was to evaluate patients on screened to the list for liver transplantation, with and without hepatocellular carcinoma, by liver elastography with Fibroscan and ARFI. METHOD: Were studied 103 adult patients from the screening for liver transplantation waiting list on the Liver and Gastrointestinal Transplant Division HC/FMUSP from October 2012 to December 2013. Sampling for convenience and evaluation clinical data, epidemiological, laboratory, imaging, elastography findings and outcome. Analysis of transient elastography (TE) by Fibroscan TM (Echosens, France) and Acoustic Radiation Force Impulse (ARFI) by (Siemens Acuson S2000, Germany) in patients with and without HCC proven in accordance with guidelines of diagnosis EASL/AASLD. Fisher\'s ANOVA or Kruskal-Wallis tests Whitney-Mann Test were performed. Tukey and define cut-of for examinations with ROC curves. The p value considered was < 0.05. RESULTS: Among the patients, the majority were men (68%), mean age 53 ± 11.5 years. This is the most common cause of hepatitis C virus (HCV) 34.9%. The classification by Child-Turcotte-Pugh score (CTP) showed: class A patients in 38.4%, 47.2% in class B and class C in 14.2%. The average value of MELD patients was 14.75 (± 6.45) and a median of 14 (range, 6-32). In the study population of 103 patients, the ET (Fibroscan) was successfully performed in 75 of 103 patients and ARFI in 78 of 78 patients. The HCV etiology and high levels of alpha-fetoprotein were risk factors for the presence of HCC. MELD values were significant higher in patients who died. The ROC curve shown respectively sensitivity and specificity for AFP of 50% and 86% (cutoff 9.1); ET (9 cutoff kPa) 92% to 17%; and ARFI 21% and 92% (cut-off 2.56 m / s). The average value of ET in HCC patients was 30.4 ± 21.0 kPa, the ARFI parenchymal liver was 1.97 ± 0.64 and ARFI liver nodules was 1.89 ± 0.74. CONCLUSION: Patients in screening for liver transplantation with hepatocellular carcinoma have elevated values of both elastography by Fibroscan as the ARFI®. Elastography is presented as an important non-invasive tool for monitoring severe cirrhosis may help in management of hepatocellular carcinoma

Le travail mené dans cette thèse s’inscrit dans la continuité des recherches sur l’élastographie par onde de cisaillement. Après un rappel bibliographique, la présentation d’une étude expérimentale montre que la résolution en élastographie par ultrasons est du même ordre de grandeur que la résolution en échographie et que sa limite dépasse la longueur d’onde de cisaillement. L’originalité de ce travail repose sur l’utilisation d’un réseau de sources mécaniques pour la génération et le contrôle des ondes de cisaillement. Un miroir à retournement temporel de six vibreurs est d’abord mis en place. Ce dispositif montre un contrôle spatio-temporel du champ élastique dans un gel gélatine-graphite. Comparé à l’utilisation d’un seul vibreur, le réseau de sources, proposé dans ce travail, améliore de 10dB le rapport signal sur bruit. L’application de cette méthode sur un modèle du crâne humain montre la possibilité de délivrer et contrôler les ondes de cisaillement dans le cerveau par conduction osseuse. Enfin, l’application de cette méthode à l’élastographie des couches abdominales est présentée par une étude sur un modèle synthétique et in vivo sur un volontaire sain / This thesis is in line with shear-wave elastography research. After, a bibliographic review, an experimental study shows that the resolution on ultrasound elastography is of the same order of magnitude of the echography resolution and its limit exceeds the shear-wavelength. The original aspect of this work is the use of a phased array of mechanical sources to generate and control shear waves. A time reversal mirror of six shakers is set up. This device shows a space-time control of shear-wave field in gelatin-graphite phantom. Compared to the use of a single source, this phased array of shear-wave improves by 10dB the signal to noise ratio. Using this method on human skull model shows the possibility to deliver and control shear waves in brain using bone conduction. Finally, the application of this method on shear-wave elastography of abdominal layers is shown by a study on synthetic model and in vivo on a healthy volunteer