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Computer models of left ventricular (LV) electro-mechanics (EM) show promise as a tool for assessing the impact of increased afterload upon LV performance. However, the identification of unique afterload model parameters and the personalization of EM LV models remains challenging due to significant clinical input uncertainties. Here, we personalized a virtual cohort of N = 17 EM LV models under pressure overload conditions. A global–local optimizer was developed to uniquely identify parameters of a three-element Windkessel (Wk3) afterload model. The sensitivity of Wk3 parameters to input uncertainty and of the EM LV model to Wk3 parameter uncertainty was analysed. The optimizer uniquely identified Wk3 parameters, and outputs of the personalized EM LV models showed close agreement with clinical data in all cases. Sensitivity analysis revealed a strong dependence of Wk3 parameters on input uncertainty. However, this had limited impact on outputs of EM LV models. A unique identification of Wk3 parameters from clinical data appears feasible, but it is sensitive to input uncertainty, thus depending on accurate invasive measurements. By contrast, the EM LV model outputs were less sensitive, with errors of less than 8.14% for input data errors of 10%, which is within the bounds of clinical data uncertainty.This article is part of the theme issue ‘Uncertainty quantification in cardiac and cardiovascular modelling and simulation’.

International audience; This work addresses the mathematical analysis - by means of asymptotic analysis - of a penalisation strategy for the full discretisation of elastic wave propagation problems in quasi-incompressible media that has been recently developed by the authors. We provide a convergence analysis of the solution of the continuous version of the penalised problem towards its formal limit when the penalisation parameter tends to infinity. Moreover, as a fundamental intermediate step we provide an asymptotic analysis of the convergence of solutions of quasi-incompressible problems towards solutions of purely incompressible problems when the incompressibility parameter tends to infinity. Finally, we further detail the regularity assumptions required to guarantee that the mentioned convergence holds.

International audience; The aim of this work is to propose a novel, fast, matrix-free solver for the Poisson problem discretised with High-Order Spectral Element Methods (HO-SEM). This method is based on the use of the Discrete Fourier Transform to reduce the problem to the inversion of the symbol of the operator in frequency space. The solver proposed is endowed with several properties. First, it preserves the efficiency of standard FFT algorithm; then, the matrix storage is minimised; a pseudo-explicit Singular Value Decomposition (SVD) is used for the inversion of the symbols; finally, it can be easily extended to multiple dimensions and non-periodic boundary conditions. In particular, due to the underlying HO-SEM discretisation, the multi-dimensional symbol of the operator can be efficiently computed from the one-dimensional symbol by tensorisation.

This PhD thesis concerns the mathematical modelling and numerical simulation of impulsive Acoustic Radiation Force (ARF)-driven Shear Wave Elastography (SWE) imaging in a prestressed soft tissue, with a specific reference to the cardiac setting. The first part of the manuscript deals with the mathematical modelling of the ARF, the resulting shear wave propagation, and the characterisation of the shear wave velocity in a general constitutive law for the myocardial tissue. We also show some applications to the extraction of fibre orientation in the myocardium and the detection of “synthetic pathologies”. One of the main contributions of this work is the derivation of an original mathematical model of the ARF. In more detail, starting from an accurate biomechanical model of the heart, and based on asymptotic analysis, we infer the governing equation of the pressure and the shear wave field remotely induced by the ARF, and we compute an analytical expression of the source term responsible for the generation of shear waves from an acoustic pressure pulse. In the second part of the PhD thesis, we propose efficient numerical tools for a realistic numerical simulation of an SWE experiment in a nearly-incompressible, pre-stressed, fibered soft tissue. The spatial discretisation is based on high-order Spectral Finite Elements (HO-SEM). Concerning the time discretisation, we propose a novel method adapted to incompressible elasticity. In particular, only the terms travelling at infinite velocity, associated with the incompressibility constraint, are treated implicitly by solving a scalar Poisson problem at each time step of the algorithm. Furthermore, we provide a novel matrix-free, high-order, fast method to solve the Poisson problem, based on the use of the Discrete Fourier Transform.; Les objectifs de cette thèse sont la modélisation mathématique et la simulation numérique de l’élastographie impulsionnelle basée sur la force de radiation acoustique (FRA) dans un tissu mou précontraint, et en particulier le myocarde. La première partie du manuscript concerne la modélisation mathématique de la FRA, la propagation d’ondes de cisaillement qui en résulte et la caractérisation de la vitesse des ondes de cisaillement pour une loi de comportement générale du tissu myocardique. Nous montrons aussi des applications pour l’estimation de l’orientation des fibres cardiaques dans le myocarde et l’évaluation de “pathologies synthétiques ”. Une des contributions principales de ce travail est le développement d’un modèle mathématique original de la FRA. En particulier, à partir d’un modèle biomécanique tridimensionnel du coeur, nous obtenons, à travers une approche asymptotique, les équations qui régissent les champs de pression et de cisaillement induits par la FRA. De plus, nous calculons une expression analytique du terme source responsable de la génération des ondes de cisaillement à partir d’une impulsion acoustique en pression. Dans la deuxième partie de la thèse, nous proposons des outils numériques efficaces pour une simulation numérique réaliste d’une expérience d’élastographie impulsionnelle dans un tissu quasi-incompressible, précontraint et fibré. La discrétisation en espace se base sur des éléments finis spectraux d’ordre élevé. Pour la discrétisation en temps, nous proposons une nouvelle méthode adaptée à l’élasticité incompressible. En particulier, seuls les termes correspondant à des vitesses infinies, associés à la contrainte d’incompressibilité, sont traités implicitement, à travers la resolution d’un problème de Poisson à chaque pas de temps de l’algorithme. En outre, nous proposons une nouvelle méthode d’ordre élevé et efficace pour la résolution d’un problème de Poisson, qui se base sur la transformée de Fourier discrète.

This PhD thesis concerns the mathematical modelling and numerical simulation of impulsive Acoustic Radiation Force (ARF)-driven Shear Wave Elastography (SWE) imaging in a prestressed soft tissue, with a specific reference to the cardiac setting. The first part of the manuscript deals with the mathematical modelling of the ARF, the resulting shear wave propagation, and the characterisation of the shear wave velocity in a general constitutive law for the myocardial tissue. We also show some applications to the extraction of fibre orientation in the myocardium and the detection of “synthetic pathologies”. One of the main contributions of this work is the derivation of an original mathematical model of the ARF. In more detail, starting from an accurate biomechanical model of the heart, and based on asymptotic analysis, we infer the governing equation of the pressure and the shear wave field remotely induced by the ARF, and we compute an analytical expression of the source term responsible for the generation of shear waves from an acoustic pressure pulse. In the second part of the PhD thesis, we propose efficient numerical tools for a realistic numerical simulation of an SWE experiment in a nearly-incompressible, pre-stressed, fibered soft tissue. The spatial discretisation is based on high-order Spectral Finite Elements (HO-SEM). Concerning the time discretisation, we propose a novel method adapted to incompressible elasticity. In particular, only the terms travelling at infinite velocity, associated with the incompressibility constraint, are treated implicitly by solving a scalar Poisson problem at each time step of the algorithm. Furthermore, we provide a novel matrix-free, high-order, fast method to solve the Poisson problem, based on the use of the Discrete Fourier Transform.; Les objectifs de cette thèse sont la modélisation mathématique et la simulation numérique de l’élastographie impulsionnelle basée sur la force de radiation acoustique (FRA) dans un tissu mou précontraint, et en particulier le myocarde. La première partie du manuscript concerne la modélisation mathématique de la FRA, la propagation d’ondes de cisaillement qui en résulte et la caractérisation de la vitesse des ondes de cisaillement pour une loi de comportement générale du tissu myocardique. Nous montrons aussi des applications pour l’estimation de l’orientation des fibres cardiaques dans le myocarde et l’évaluation de “pathologies synthétiques ”. Une des contributions principales de ce travail est le développement d’un modèle mathématique original de la FRA. En particulier, à partir d’un modèle biomécanique tridimensionnel du coeur, nous obtenons, à travers une approche asymptotique, les équations qui régissent les champs de pression et de cisaillement induits par la FRA. De plus, nous calculons une expression analytique du terme source responsable de la génération des ondes de cisaillement à partir d’une impulsion acoustique en pression. Dans la deuxième partie de la thèse, nous proposons des outils numériques efficaces pour une simulation numérique réaliste d’une expérience d’élastographie impulsionnelle dans un tissu quasi-incompressible, précontraint et fibré. La discrétisation en espace se base sur des éléments finis spectraux d’ordre élevé. Pour la discrétisation en temps, nous proposons une nouvelle méthode adaptée à l’élasticité incompressible. En particulier, seuls les termes correspondant à des vitesses infinies, associés à la contrainte d’incompressibilité, sont traités implicitement, à travers la resolution d’un problème de Poisson à chaque pas de temps de l’algorithme. En outre, nous proposons une nouvelle méthode d’ordre élevé et efficace pour la résolution d’un problème de Poisson, qui se base sur la transformée de Fourier discrète.

International audience; The principal aim of this work is to provide an adapted numerical scheme for the approximation of elastic wave propagation in incompressible solids. We rely on high-order conforming finite element with mass lumping for space discretisation and implicit/explicit, second-order, energy-preserving time discretisation. The time step restriction only depends on the shear wave velocity and at each time step a Poisson problem must be solved to account for the incompressibility constraint that is imposed by penalisation techniques.

This work presents a detailed investigation of a parameter estimation approach based on the reduced order unscented Kalman filter (ROUKF) in the context of one-dimensional blood flow models. In particular, the main aims of this study are (i) to investigate the effect of using real measurements vs. synthetic data (i.e., numerical results of the same in silico model, perturbed with white noise) for the estimation and (ii) to identify potential difficulties and limitations of the approach in clinically realistic applications in order to assess the applicability of the filter to such setups. For these purposes, our numerical study is based on the in vitro model of the arterial network described by [Alastruey et al. 2011, J. Biomech. bf 44], for which experimental flow and pressure measurements are available at few selected locations. In order to mimic clinically relevant situations, we focus on the estimation of terminal resistances and arterial wall parameters related to vessel mechanics (Young's modulus and thickness) using few experimental observations (at most a single pressure or flow measurement per vessel). In all cases, we first perform a theoretical identifiability analysis based on the generalized sensitivity function, comparing then the results obtained with the ROUKF, using either synthetic or experimental data, to results obtained using reference parameters and to available measurements.