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Biomechanical modeling and simulation is expected to play a significant role in the development of the next generation tools in many fields of medicine. However, full-fledged finite element models of complex organs such as the heart can be computationally very expensive, thus limiting their practical usability. Therefore, reduced models are much valuable to be used, e.g., for pre-calibration of full-fledged models, fast predictions, real-time applications, etc.. In this work, focused on the left ventricle, we develop a reduced model by defining reduced geometry & kinematics while keeping general motion and behavior laws, allowing to derive a reduced model where all variables & parameters have a strong physical meaning. More specifically, we propose a reduced ventricular model based on cylindrical geometry & kinematics, which allows to describe the myofiber orientation through the ventricular wall and to represent contraction patterns such as ventricular twist, two important features of ventricular mechanics. Our model is based on the original cylindrical model of [Guccione, McCulloch, & Waldman 1991; Guccione, Waldman, & McCulloch 1993], albeit with multiple differences: we propose a fully dynamical formulation, integrated into an open-loop lumped circulation model, and based on a material behavior that incorporates a fine description of contraction mechanisms; moreover, the issue of the cylinder closure has been completely reformulated; our numerical approach is novel as well, with consistent spatial (finite element) and time discretizations. Finally, we analyse the sensitivity of the model response to various numerical and physical parameters, and study its physiological response.

International audience; Muscle contraction is triggered by the activation of the actin sites of the thin filament by calcium ions. It results that the thin filament activation level varies over time. Moreover, this activation process is also used as a regulation mechanism of the developed force. Our objective is to build a model of varying actin site activation level within the classical Huxley'57 two-state framework. This new model is obtained as an enhancement of a previously proposed formulation of the varying thick filament activation within the same framework [1]. We assume that the state of an actin site depends on whether it is activated and whether it forms a cross-bridge with the associated myosin head, which results in four possible states. The transitions between the actin site states are controlled by the global actin sites activation level and the dynamics of these transitions is coupled with the attachment-detachment process. A preliminary calibration of the model with experimental twitch contraction data obtained at varying sarcomere lengths is performed.

Pulmonary function is tightly linked to the lung mechanical behavior, especially large deformation during breathing. Interstitial lung diseases, such as idiopathic pulmonary fibrosis (IPF), have an impact on the pulmonary mechanics and consequently alter lung function. However, IPF remains poorly understood, poorly diagnosed, and poorly treated. Currently, the mechanical impact of such diseases is assessed by pressure–volume curves, giving only global information. We developed a poromechanical model of the lung that can be personalized to a patient based on routine clinical data. The personalization pipeline uses clinical data, mainly computed tomography (CT) images at two time steps and involves the formulation of an inverse problem to estimate regional compliances. The estimation problem can be formulated both in terms of “effective”, i.e., without considering the mixture porosity, or “rescaled,” i.e., where the first-order effect of the porosity has been taken into account, compliances. Regional compliances are estimated for one control subject and three IPF patients, allowing to quantify the IPF-induced tissue stiffening. This personalized model could be used in the clinic as an objective and quantitative tool for IPF diagnosis.

This PhD thesis is an interdisciplinary research that deals with applied biomechanical modeling of the cardiovascular system in patients with congenital heart diseases . The aim is to explore the potential of biomechanical modeling to assist in clinical decision-making.First, we explored the ability of a previously developed biomechanical model to augment the interpretation of clinical data for patients with tetralogy of Fallot after repair (rTOF) prior to and after pulmonary valve replacement (PVR). Patient-specific models of the right ventricle (RV) and pulmonary circulation were built for 20 subjects pre- and post-PVR using cardiovascular magnetic resonance (CMR) and pressure catheter data. These models were subjected to the effects of pulmonary valve (PV) regurgitation and/or RV outflow tract (RVOT) obstruction. The models provided patient-specific indices of myocardial contractility pre- and post-PVR. The results showed a decrease of contractility in all patients post-PVR. Patients with predominantly RVOT obstruction experienced a higher level of contractility decrease whereas ceasing the regurgitation itself did not lead to a significant reduction in contractility. After this detailed study of pathophysiology of the overloaded RVs pre- and post-PVR, we explored the ability of the model to predict the response of ventricular mechanics when progressively decreasing the afterload of the RVs in patients with rTOF. Pre-PVR patient-specific models were used and cessation of PV regurgitation and progressive decrease of RVOT resistance were assumed. The resulting in silico relationships between the contractility and RVOT resistance post-PVR appeared to be linear, and consistent with that given by the patient-specific post-PVR models.For patients with single-ventricle hearts undergoing CMR combined with a pressure catheter (as part of planning for complex surgery), the model was used to synchronize in time the catheter-pressure data and the ventricular volumes obtained by CMR. This model-assisted time-synchronization produces high quality P-V loops that yield more accurate indices of myocardial energetics (maximum value of time-varying elastance (E_max) and stroke work) and hence could be used to ameliorate the clinical interpretation.Finally, we compared the indices of E_max and maximum time derivative of ventricular pressure, max(dP/dt), when obtained directly from the clinical measurements vs. model-derived contractility and max(dP/dt). All data- and model-derived indices showed a good agreement. In addition, a potential application of model-derived max⁡(dP/dt) as a model-based data filter was emphasized.Overall, this thesis demonstrated (1) an ability of biomechanical modeling to provide additional mechanical indices of ventricular function and their evolution under different loading conditions, which has the potential to contribute into the planning of optimal therapy; (2) an application of the model to provide robust clinical data processing of a variety of data acquisition protocols; and (3) a correspondence of model-derived indices with clinically accepted surrogate measures of contractility. In conclusion, this thesis showed that biomechanical modeling could be deployed in a clinical environment to address various types of problems towards the delivery of personalized healthcare solutions.; Cette thèse de doctorat est une recherche interdisciplinaire qui porte sur la modélisation biomécanique appliquée du système cardiovasculaire chez les patients atteints de cardiopathies congénitales. L'objectif est d'explorer le potentiel de la modélisation biomécanique pour aider à la prise de décision clinique.Tout d'abord, nous avons exploré la capacité d'un modèle biomécanique précédemment développé à améliorer l'interprétation des données cliniques pour les patients atteints de tétralogie de Fallot après réparation (TOFr) avant et après le remplacement de la valve pulmonaire (RVP). Des modèles personnalisés du ventricule droit (VD) et de la circulation pulmonaire ont été construits pour 20 sujets avant et après le RVP à l'aide de données obtenues par résonance magnétique cardiovasculaire (RMC) et par cathéter de pression. Ces modèles ont été soumis aux effets de la régurgitation de la valve pulmonaire (VP) et/ou de l'obstruction du canal de sortie du VD (RVOT). Les modèles ont fourni des indices de contractilité myocardique personnalisés avant et après la RPV. Les résultats ont montré une diminution de la contractilité chez tous les patients après la RVP. Les patients présentant une obstruction prédominante de l'RVOT ont connu une diminution plus importante de la contractilité, alors que l'arrêt de la régurgitation elle-même n'a pas entraîné de réduction significative de la contractilité. Après cette étude détaillée de la pathophysiologie des VD surchargés avant et après la RVP, nous avons exploré la capacité du modèle à prédire la réponse de la mécanique ventriculaire lors de la diminution progressive de la post-charge des VD chez les patients atteints de TOFr. Des modèles pré-PVR personnalisés ont été utilisés et l'arrêt de la régurgitation PV et la diminution progressive de la résistance RVOT ont été supposés. Les relations in silico résultantes entre la contractilité et la résistance de l'RVOT après la RVP sont apparues linéaires et cohérentes avec celles données par les modèles post-RVP spécifiques aux patients.Pour les patients dont le cœur est constitué d'un seul ventricule et qui subissent une RMC combinée à un cathéter de pression (dans le cadre de la planification d'une chirurgie complexe), le modèle a été utilisé pour synchroniser dans le temps les données de pression du cathéter et les volumes ventriculaires obtenus par RMC. Cette synchronisation temporelle assistée par le modèle produit des boucles P-V de haute qualité qui donnent des indices plus précis de l'énergétique cardiaque (valeur maximale de l'élastance variable dans le temps (E_max) et du travail systémique) et qui pourraient donc être utilisés pour améliorer l'interprétation clinique.Enfin, nous avons comparé les indices de E_max et de la dérivée temporelle maximale de la pression ventriculaire, max(dP/dt), obtenus directement à partir des mesures cliniques, avec la contractilité et le max(dP/dt) dérivés du modèle. Tous les indices dérivés des données et du modèle ont montré une bonne concordance. De plus, une application potentielle du max(dP/dt) dérivé du modèle comme filtre de données basé sur le modèle a été soulignée.Dans l'ensemble, cette thèse a démontré (1) la capacité de la modélisation biomécanique à fournir des indices mécaniques supplémentaires de la fonction ventriculaire et leur évolution dans différentes conditions de charge, ce qui pourrait contribuer à la planification d'une thérapie optimale ; (2) une application du modèle pour fournir un traitement robuste des données cliniques d'une variété de protocoles d'acquisition de données ; et (3) une correspondance des indices dérivés du modèle avec des mesures de substitution de la contractilité acceptées cliniquement. En conclusion, cette thèse a montré que la modélisation biomécanique pouvait être déployée dans un environnement clinique pour résoudre divers types de problèmes en médecine personnalisée.