Bhattacharya-Ghosh, B; (2014) Development of a multi-scale and multi-physics model of the left ventricle and its application in 0D and 3D. Doctoral thesis , UCL (University College London).

Abstract

This thesis describes the development of a multi-scale and multi-physics model of the left ventricle in silico. The model presented here, provides a computational model that allows further insight into the events and mechanism describing the ventricular contraction and relaxation (excitation contraction coupling process) at low computational costs. The formalisms and methods describing the electro-mechanical coupling (from intracellular, to electrical, to flow, to physiology mechanisms) across the scales are presented in a novel manner, coherently combining the various processes of all scales from a biological and mathematical point of view. The multiple scales involved in the model encompass the protein, cellular and organ level. In order to achieve this, at each scale the typical characteristics and mechanisms, such as the Action Potential, cross-bridge kinetics, pressure-volume relationship are simulated, extrapolating the behaviour of a ventricular cardiomyocyte to the whole ventricle. The coupling between the three scales presented is achieved via two links, the intracellular calcium concentration and the cross-bridge kinetics. The generation of force calculated at the organ level gives further insight on the cardiovascular haemodynamics, such as changes in pressure, flow and volume. In collaboration with TU/e, Netherlands, the presented multi-scale and multi-physics model of the left ventricle (developed in MATLAB) is expanded to a whole heart model in SIMULINK, enabling to investigate the behaviour of a healthy heart. Following, a case study of idiopathic dilated cardiomyopathy is conducted. While mainly the effects of idiopathic dilated cardiomyopathy (IDC) are presented in literature, it lacks of quantitative data to describe these effects. To simulate the effects of IDC, as shown in corresponding literature, key parameters across all scales were chosen and modified in the multi-scale model of the heart. A second collaboration with ANSYS UK demonstrates the feasibility of the ventricular multi-scale and multi-physics model as a boundary condition, being coupled to a 3D Model in ANSYS. The interaction and exchange of ventricular pressure and mitral flow between MATLAB and ANSYS, respectively, drives the local haemodynamics of the mitral valve in a CFX model. The 0D-3D coupling sets a foundation and coupling technique that can be further expanded to other models and conduct case studies on pathologies of the heart.

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