Le cancer du sein est le cancer le plus fréquent chez les femmes. Il y a une multitude de solutions proposées concernant une éventuelle intervention médicale pour le cancer du sein ‐ une en particulier est la chirurgie mammaire conservatrice (tumoréctomie). Le but de la tumoréctomie est de parvenir à un contrôle local du cancer, ainsi que de préserver une forme du sein qui satisfait les besoins esthétiques de la femme. Bien que ces objectifs sont généralement atteint, il reste encore parfois des résultats inattendus,tels qu'une tumeur récurrence locale, ou des résultats cosmétiques insuffisants.L'objectif de cette thèse est de proposer une plateforme de calcul, qui contribue à la tumoréctomie. Cela comprend:1) Une étude de la dynamique de croissance des tumeurs du sein.2) Une étude sur la prédiction du contour du sein grâce a la chirurgie virtuelle.3) Un modèle de calcul de la forme finale du sein après cicatrisation. / Breast cancer is the most common cancer among women in the developed as well as the developing countries. There are a plethora of proposed solutions regarding possible medical interventions for breast cancer–one in particular is Breast Conserving Therapy (BCT). BCT comprises of complete surgical excision of the tumor (partialmastectomy), and post-operative radiotherapy for the remaining breast tissue. This is a feasible treatment for most women with breast cancer. The goal of BCT is toachieve local control of the cancer, as well as to preserve breast shape that appeases awoman’s cosmetic concerns. Although these goals are usually achieved, there are still occasional unexpected results, such as reexcision of the tumor due to a positive margin assessment, tumor local recurrence, unsatisfactory cosmetic results, and breastpain. Other than surgical experience and judgment, there are currently no toolswhich can predict the outcome of partial mastectomy on the contour and deformity of the treated breast. The objective of this dissertation is to propose computational framework, which contributes to BCT operations, this was achieve by exploring two areas.On the one hand we developed a multiscale model adapted for breast cancer tumor growth, ductal carcinoma in situ (DCIS). The model features included: nutrients growth limitation, wall degradation enzyme and HER2 chemical expression tumor phenotype. Our model successfully simulate some pattern of DCIS carcinoma.Among the interesting result we showed that the enzyme contributed to a greater tumor size and that when HER2 was over expressed, the growth limiting factor wasthe EGFR. On the other hand, we developed a virtual surgery box to simulate BCT surgery. The box will input MRI patient data and will output cosmetic and functional indicator to rate the impact of the surgery. It appears that stiffness of the tissue, resection radius as well as the lump quadrant location are the most sensitive parameters to the indicators. A healing model was also embedded to simulate the wound closure after resection, this model was stress dependent and illustrate anasymmetric wound closure progression.The tools developed in this research allows a new type of field convergence between the surgery and computation field. At the local level it will allow surgeons and patient to be able to communicate on the pertinence and necessity of performing alumpectomy surgery, enabling to anticipate the possible outcome of the operation.On the global aspect this type of tool gives birth to a new type of field: computational surgery, where computer scientist and surgeons work hand in hand to provide the best and the most reliable service to the patients.

This thesis is focused on stress in brain aneurysms. It consists of three parts. First part is aimed for gaining information about the topic from scientific resources. Next part consists of analyses of geometry of cerebral aneurysms on the computed wall stress. Analyses are performed on four basic geometrical models and results are being discussed. The risky areas in each investigated shape have been identified as well as the comparisons of stress between those shapes have been performed and the most dangerous shape among investigated shapes has been determined. Third part investigates the influence of surrounding tissue on the brain aneurysm. Conclusion of this thesis is that brain gray tissue has positive yet negligible effect on the computed wall stress.

Ultrasonic measurements of the preload in bolted joints is a very accurate method since it does not depend on the friction and other factors which cause difficulties for common methods. The ultrasonic method works by emitting an ultrasonic pulse into the bolt which is reflected at the end and returned to the transducer, the change in the time of flight (TOF) can be related to the elongation of the bolt and therefore the preload. One must account for the acoustoelastic effect which is the change in sound speed due to an initial stress state. The goal of this thesis project was to implement a Murnaghan hyperelastic material model in order to account for the acoustoelastic effect when conducting a numerical simulation using the finite element method (FEM). An experiment was also performed to validate the numerical simulation. The DeltaTOF as a function of a tensile force was obtained for an M8 and M10 test piece from the experiment. The material model was implemented by creating a user subroutine written in Fortran for the explicit solver Radioss. Hypermesh was used to set-up the numerical simulation. The material model has shown an expected behavior with an increased sound speed with compressive stresses and a decreased speed with tensile stresses. The numerical simulation showed a good correspondence to the experimental results. / Ultraljudsmätning av klämklraften i skruvförband är en väldigt noggrann metod eftersom att metoden inte påverkas av friktion eller andra faktorer som innebär svårigheter för vanliga metoder. Ultraljudsmetoden fungerar genom att skicka in en ultraljudsvåg i skruven som reflekteras i botten och återvänder tillbaka till sensorn. Skillnaden i tiden för ekot att återvända kan relateras till förlängningen av skruven och därmed klämkraften. Det är viktigt att ta hänsyn till den akustoelastiska effekten, som är fenomenet där ljudhastigheten av en våg i en solid förändras med spänningstillståndet. Målet med det här arbetet är att implementera en hyperelastisk Murnaghan modell som tar hänsyn till den akustoelastiska effekten med FEM simuleringar. Ett experiment har också genomförts för att validera beräkningsmodellen. Tidsfördröjningen som en funktion av förspänningskraften togs fram för ett M8 och M10 provobjekt. Murnaghans hyperelastiska materialmodell implementerades genom att skapa ett användar material skriven i programmeringsspråket Fortran för den explicita lösaren Radioss. Hypermesh användes för att ställa upp FEM simuleringen. Materialmodellen har visat ett väntat beteende med en ökad ljudhastighet med tryckspänningar och minskad ljudhastighet med dragspänningar. Beräkningsmodellen visade en god överenstämmelse med resultatet från experimentet.

Part 1: Theoretic background information - Review of Hooke’s law for linear elastic materials - The strain energy density of linear elastic materials - Hyperelastic material - Material laws for hyperelastic materials - About selecting the material model and performing tests - Implementation of hyperelastic material laws in Mechanica - Defining hyperelastic material parameters in Mechanica - Test set-ups and specimen shapes of the supported material tests - The uniaxial compression test - Stress and strain definitions in the Mechanica LDA analysis Part 2: Application examples - A test specimen subjected to uniaxial loading - A volumetric compression test - A planar test - Influence of the material law Appendix - PTC Simulation Services Introduction - Dictionary Technical English-German / Teil 1: Theoretische Hintergrundinformation - Das Hookesche Gesetz für linear-elastische Werkstoffe - Die Dehnungsenergiedichte für linear-elastische Materialien - Hyperelastisches Material - Materialgesetze für Hyperelastizität - Auswählen des Materialgesetzes und Testdurchführung - Implementierung der hyperelastischen Materialgesetze in Mechanica - Definieren der hyperelastischen Materialparameter in Mechanica - Testaufbauten und Prüfkörper der unterstützten Materialtests - Der einachsige Druckversuch - Spannungs- und Dehnungsdefinition in der Mechanica-Analyse mit großen Verformungen Teil 2: Anwendungsbeispiele - Ein einachsig beanspruchter Prüfkörper - Ein volumetrischer Drucktest - Ein planarer Test - Einfluss des Materialgesetzes Anhang: - Kurzvorstellung der PTC Simulationsdienstleistungen - Wörterbuch technisches Englisch-Deutsch

Part 1: Theoretic background information - Review of Hooke’s law for linear elastic materials - The strain energy density of linear elastic materials - Hyperelastic material - Material laws for hyperelastic materials - About selecting the material model and performing tests - Implementation of hyperelastic material laws in Mechanica - Defining hyperelastic material parameters in Mechanica - Test set-ups and specimen shapes of the supported material tests - The uniaxial compression test - Stress and strain definitions in the Mechanica LDA analysis Part 2: Application examples - A test specimen subjected to uniaxial loading - A volumetric compression test - A planar test - Influence of the material law Appendix - PTC Simulation Services Introduction - Dictionary Technical English-German / Teil 1: Theoretische Hintergrundinformation - Das Hookesche Gesetz für linear-elastische Werkstoffe - Die Dehnungsenergiedichte für linear-elastische Materialien - Hyperelastisches Material - Materialgesetze für Hyperelastizität - Auswählen des Materialgesetzes und Testdurchführung - Implementierung der hyperelastischen Materialgesetze in Mechanica - Definieren der hyperelastischen Materialparameter in Mechanica - Testaufbauten und Prüfkörper der unterstützten Materialtests - Der einachsige Druckversuch - Spannungs- und Dehnungsdefinition in der Mechanica-Analyse mit großen Verformungen Teil 2: Anwendungsbeispiele - Ein einachsig beanspruchter Prüfkörper - Ein volumetrischer Drucktest - Ein planarer Test - Einfluss des Materialgesetzes Anhang: - Kurzvorstellung der PTC Simulationsdienstleistungen - Wörterbuch technisches Englisch-Deutsch

Calcific aortic valve disease (CAVD) is one of the most common causes of cardiovascular disease in North America. Mechanical factors have been closely linked to the pathogenesis of CAVD and may contribute to the disease by actively regulating the mechanobiology of valve interstitial cells (VICs). Mechanical forces affect VIC function through interactions between the VIC and the extracellular matrix (ECM). Studies have shown that the transfer of mechanical stimulus during cell-ECM interaction depends on the local material properties at hierarchical length scales encompassing tissue, cell and cytoskeleton. In this thesis, biomechanical tools were developed and applied to investigate hierarchical cell-ECM interactions, using VICs and valve tissue as a model system. Four topics of critical importance to understanding VIC-ECM interactions were studied: focal biomechanical material properties of aortic valve tissue; viscoelastic properties of VICs; transduction of mechanical deformation from the ECM to the cytoskeletal network; and the impact of altered cell-ECM interactions on VIC survival. To measure focal valve tissue properties, a micropipette aspiration (MA) method was implemented and validated. It was found that nonlinear elastic properties of the top layer of a multilayered biomaterial can be estimated by MA by using a pipette with a diameter smaller than the top layer thickness. Using this approach, it was shown that the effective stiffness of the fibrosa layer is greater than that of the ventricularis layer in intact aortic valve leaflets (p<0.01). To characterize the viscoelastic properties of VICs, an inverse FE method of single cell MA was developed and compared with the analytical half-space model. It was found that inherent differences in the half-space and FE models of single cell MA yield different cell viscoelastic material parameters. However, under particular experimental conditions, the parameters estimated by the half-space model are statistically indistinguishable from those predicted by the FE model. To study strain transduction from the ECM to cytoskeleton, an improved texture correlation algorithm and a uniaxial tension release device were developed. It was found that substrate strain fully transfers to the cytoskeletal network via focal adhesions in live VICs under large strain tension release. To study the effects of cell-ECM interactions on VIC survival, two mechanical stimulus systems that can simulate the separate effects of cell contraction and cell monolayer detachment were developed. It was found that cell sheet detachment and disrupted cell-ECM signaling is likely responsible for the apoptosis of VICs grown in culture on thin collagen matrices, leading to calcification. The studies presented in this thesis refine existing biomechanical tools and provide new experimental and analytical tools with which to study cell-ECM interactions. Their application resulted in an improved understanding of hierarchical valve biomechanics, mechanotransduction, and mechanobiology.

Calcific aortic valve disease (CAVD) is one of the most common causes of cardiovascular disease in North America. Mechanical factors have been closely linked to the pathogenesis of CAVD and may contribute to the disease by actively regulating the mechanobiology of valve interstitial cells (VICs). Mechanical forces affect VIC function through interactions between the VIC and the extracellular matrix (ECM). Studies have shown that the transfer of mechanical stimulus during cell-ECM interaction depends on the local material properties at hierarchical length scales encompassing tissue, cell and cytoskeleton. In this thesis, biomechanical tools were developed and applied to investigate hierarchical cell-ECM interactions, using VICs and valve tissue as a model system. Four topics of critical importance to understanding VIC-ECM interactions were studied: focal biomechanical material properties of aortic valve tissue; viscoelastic properties of VICs; transduction of mechanical deformation from the ECM to the cytoskeletal network; and the impact of altered cell-ECM interactions on VIC survival. To measure focal valve tissue properties, a micropipette aspiration (MA) method was implemented and validated. It was found that nonlinear elastic properties of the top layer of a multilayered biomaterial can be estimated by MA by using a pipette with a diameter smaller than the top layer thickness. Using this approach, it was shown that the effective stiffness of the fibrosa layer is greater than that of the ventricularis layer in intact aortic valve leaflets (p<0.01). To characterize the viscoelastic properties of VICs, an inverse FE method of single cell MA was developed and compared with the analytical half-space model. It was found that inherent differences in the half-space and FE models of single cell MA yield different cell viscoelastic material parameters. However, under particular experimental conditions, the parameters estimated by the half-space model are statistically indistinguishable from those predicted by the FE model. To study strain transduction from the ECM to cytoskeleton, an improved texture correlation algorithm and a uniaxial tension release device were developed. It was found that substrate strain fully transfers to the cytoskeletal network via focal adhesions in live VICs under large strain tension release. To study the effects of cell-ECM interactions on VIC survival, two mechanical stimulus systems that can simulate the separate effects of cell contraction and cell monolayer detachment were developed. It was found that cell sheet detachment and disrupted cell-ECM signaling is likely responsible for the apoptosis of VICs grown in culture on thin collagen matrices, leading to calcification. The studies presented in this thesis refine existing biomechanical tools and provide new experimental and analytical tools with which to study cell-ECM interactions. Their application resulted in an improved understanding of hierarchical valve biomechanics, mechanotransduction, and mechanobiology.

La simulation des procédés de mise en forme des composites à renforts tissés de type RTM est un enjeu majeur pour les industries de pointe mettant en œuvre ce type de matériaux. Au cours de ces procédés, la préforme tissée est souvent soumise à des déformations importantes. La connaissance et la simulation du comportement mécanique de la préforme à l’échelle macroscopique et à l’échelle mésoscopique s’avère souvent nécessaire pour optimiser la phase de conception de pièces composites formées par de tels procédés. Une analyse du comportement mésoscopique des préformes tissées de composites est d’abord proposée. Une loi de comportement hyperélastique isotrope transverse est développée, permettant de décrire le comportement mécanique de chacun des modes de déformation de la mèche : élongation dans la direction des fibres, compaction et distorsion dans le plan d’isotropie de la mèche, cisaillement le long des fibres. Une méthodologie est proposée pour identifier les paramètres de cette loi de comportement à l’aide d’essais sur la mèche et sur le tissu, et une validation par comparaison avec des essais expérimentaux est présentée. Une analyse du comportement macroscopique des renforts interlocks est ensuite proposée : une loi de comportement hyperélastique orthotrope est développée et implémentée. Cette loi, extension de la loi de comportement pour la mèche, est également basée sur une description phénoménologique des modes de déformation de la préforme. Une méthode d’identification des paramètres de cette loi de comportement est mise en œuvre, utilisant des essais expérimentaux classiques dans le contexte des renforts tissés (tension uniaxiale, compression, bias extension test, flexion). Cette seconde loi de comportement est validée par comparaison avec des essais de flexion et d’emboutissage hémisphérique. / Simulating the preforming stage of RTM-like fabric-reinforced composites manufactoring processes is a major stake for industries which use such materials. During such processes, the woven preform often undergoes finite deformations. Simulation methods are then required to optimize the conception of composites parts formed by RTM. An analysis of the mechanical behaviour of woven preforms at mesoscale is first presented. A transversely isotropic hyperelastic behaviour law is developped in order to describe the mechanical behaviour of each deformation mode of the yarn : elongation in the direction of fibres, compaction and distorsion in the transverse plane and along-fibres shear. An identification method is set up for this behaviour law which allows to compute its parameters by use of simple experimental tests on the yarn and on the fabric. The behaviour law is then validated by comparizon between simulations ans experimental tests. An analysis of the mechanical behaviour of interlock woven preforms at macroscale is the presented. An orthotropic hyperelastic behaviour law is developped and implemented as an extension of the behaviour law for the yarn. A phenomenological approach is also used to describe the mechanical behaviour of each deformation mode of the preform. An identification method is set up and put into place, based on tests well known in the field of fabric reinforcements : tensile test, crushing test, bias extension test, flexure test. A hemispherical stamping simulation is set up and compared to experiment for validation purpose.

Afin de pouvoir prédire le comportement des renforts de composites 3D interlock au cours d'un procédé de mise en forme, il est nécessaire de connaitre la position des mèches dans le renfort durant la phase de préformage du procédé. Les travaux présentés ici traitent de la simulation du préformage de renforts 3D épais à l'aide d'un élément fini hexaédrique semi-discret spécifique. En utilisant le principe des travaux virtuels, on distingue le travail interne virtuel dû à la tension des mèches des autres travaux virtuels. La raideur due aux tensions de mèches, qui constitue la contribution principale de la rigidité du matériau, est prise en compte à l'aide de barres incluses dans les éléments. Les rigidités dues aux autres sollicitations, comme la compression transverse, les cisaillements ou les frottements inter-mèches, sont décrites par un matériau continu additionnel. La combinaison de ce modèle discret du premier ordre et d'un matériau continu hyperélastique anisotrope dit du second ordre, pour formuler le comportement du matériau va permettre la simulation du préformage des renforts tissés épais. Conjointement aux travaux sur la simulation, des travaux expérimentaux pour l'identification des paramètres matériau de la loi de comportement ont été définis et réalisés. Ces paramètres concernent les deux parties de la formulation du comportement. / In order to simulate 3D interlock composite reinforcement behavior during forming process, it is necessary to predict yarns positions in the fabric during the preforming stage of the process. The present work deals with thick 3D interlock fabric forming simulation using specific hexahedral semi-discrete finite elements. Using the virtual work principle, we distinguish the virtual internal work due to tensions in yarns from other internal virtual works. The stiffness relative to yarns tension which is the main part of the rigidity is described by bars within the elements. The other rigidities - like transverse compression, shears or friction between yarns - are depicted by a continuous additional material. A combination of this "first order" discrete model and a continuous orthotropic hyperelastic "second order" material formulation will enable us to simulate the interlock preforming process. Jointly to the simulation work, we also had to specify and perform experimental testing identification of material parameters. These parameters concern both parts of the model.

Part 1: Theoretic background information - Review of Hooke’s law for linear elastic materials - The strain energy density of linear elastic materials - Hyperelastic material - Material laws for hyperelastic materials - About selecting the material model and performing tests - Implementation of hyperelastic material laws in Mechanica - Defining hyperelastic material parameters in Mechanica - Test set-ups and specimen shapes of the supported material tests - The uniaxial compression test - Stress and strain definitions in the Mechanica LDA analysis Part 2: Application examples - A test specimen subjected to uniaxial loading - A volumetric compression test - A planar test - Influence of the material law Appendix - PTC Simulation Services Introduction - Dictionary Technical English-German / Teil 1: Theoretische Hintergrundinformation - Das Hookesche Gesetz für linear-elastische Werkstoffe - Die Dehnungsenergiedichte für linear-elastische Materialien - Hyperelastisches Material - Materialgesetze für Hyperelastizität - Auswählen des Materialgesetzes und Testdurchführung - Implementierung der hyperelastischen Materialgesetze in Mechanica - Definieren der hyperelastischen Materialparameter in Mechanica - Testaufbauten und Prüfkörper der unterstützten Materialtests - Der einachsige Druckversuch - Spannungs- und Dehnungsdefinition in der Mechanica-Analyse mit großen Verformungen Teil 2: Anwendungsbeispiele - Ein einachsig beanspruchter Prüfkörper - Ein volumetrischer Drucktest - Ein planarer Test - Einfluss des Materialgesetzes Anhang: - Kurzvorstellung der PTC Simulationsdienstleistungen - Wörterbuch technisches Englisch-Deutsch