Influence of cardiac tissue anisotropy on re-entrant activation in computational models of ventricular fibrillation

The aim of this study was to establish the role played by anisotropic diffusion in (i) the number of filaments and epicardial phase singularities that sustain ventricular fibrillation in the heart, (ii) the lifetimes of filaments and phase singularities, and (iii) the creation and annihilation dynamics of filaments and phase singularities. A simplified monodomain model of cardiac tissue was used, with membrane excitation described by a simplified 3-variable model. The model was configured so that a single re-entrant wave was unstable, and fragmented into multiple re-entrant waves. Re-entry was then initiated in tissue slabs with varying anisotropy ratio. The main findings of this computational study are: (i) anisotropy ratio influenced the number of filaments Sustaining simulated ventricular fibrillation, with more filaments present in simulations with smaller values of transverse diffusion coefficient, (ii) each re-entrant filament was associated with around 0.9 phase singularities on the surface of the slab geometry, (iii) phase singularities were longer lived than filaments, and (iv) the creation and annihilation of filaments and phase singularities were linear functions of the number of filaments and phase singularities, and these relationships were independent of the anisotropy ratio. This study underscores the important role played by tissue anisotropy in cardiac ventricular fibrillation

A pseudo active kinematic constraint for a biological living soft tissue: an effect of the collagen network

Recent studies in mammalian hearts show that left ventricular wall thickening is an important mechanism for systolic ejection and that during contraction the cardiac muscle develops significant stresses in the muscular cross-fiber direction. We suggested that the collagen network surrounding the muscular fibers could account for these mechanical behaviors. To test this hypothesis we develop a model for large deformation response of active, incompressible, nonlinear elastic and transversely isotropic living soft tissue (such as cardiac or arteries tissues) in which we include a coupling effect between the connective tissue and the muscular fibers. Then, a three-dimensional finite element formulation including this internal pseudo-active kinematic constraint is derived. Analytical and finite element solutions are in a very good agreement. The numerical results show this wall thickening effect with an order of magnitude compatible with the experimental observations

Structure-based finite strain modelling of the human left ventricle in diastole

Finite strain analyses of the left ventricle provide important information on heart function and have the potential to provide insights into the biomechanics of myocardial contractility in health and disease. Systolic dysfunction is the most common cause of heart failure; however, abnormalities of diastolic function also contribute to heart failure, and are associated with conditions including left ventricular hypertrophy and diabetes. The clinical significance of diastolic abnormalities is less well understood than systolic dysfunction, and specific treatments are presently lacking. To obtain qualitative and quantitative information on heart function in diastole, we develop a three-dimensional computational model of the human left ventricle that is derived from noninvasive imaging data. This anatomically realistic model has a rule-based fibre structure and a structure-based constitutive model. We investigate the sensitivity of this comprehensive model to small changes in the constitutive parameters and to changes in the fibre distribution. We make extensive comparisons between this model and similar models that employ different constitutive models, and we demonstrate qualitative and quantitative differences in stress and strain distributions for the different constitutive models. We also provide an initial validation of our model through comparisons to experimental data on stress and strain distributions in the left ventricle

Stability and energy budget of pressure-driven collapsible channel flows

Although self-excited oscillations in collapsible channel flows have been extensively studied, our understanding of their origins and mechanisms is still far from complete. In the present paper, we focus on the stability and energy budget of collapsible channel flows using a fluid–beam model with the pressure-driven (inlet pressure specified) condition, and highlight its differences to the flow-driven (i.e. inlet flow specified) system. The numerical finite element scheme used is a spine-based arbitrary Lagrangian–Eulerian method, which is shown to satisfy the geometric conservation law exactly. We find that the stability structure for the pressure-driven system is not a cascade as in the flow-driven case, and the mode-2 instability is no longer the primary onset of the self-excited oscillations. Instead, mode-1 instability becomes the dominating unstable mode. The mode-2 neutral curve is found to be completely enclosed by the mode-1 neutral curve in the pressure drop and wall stiffness space; hence no purely mode-2 unstable solutions exist in the parameter space investigated. By analysing the energy budgets at the neutrally stable points, we can confirm that in the high-wall-tension region (on the upper branch of the mode-1 neutral curve), the stability mechanism is the same as proposed by Jensen and Heil. Namely, self-excited oscillations can grow by extracting kinetic energy from the mean flow, with exactly two-thirds of the net kinetic energy flux dissipated by the oscillations and the remainder balanced by increased dissipation in the mean flow. However, this mechanism cannot explain the energy budget for solutions along the lower branch of the mode-1 neutral curve where greater wall deformation occurs. Nor can it explain the energy budget for the mode-2 neutral oscillations, where the unsteady pressure drop is strongly influenced by the severely collapsed wall, with stronger Bernoulli effects and flow separations. It is clear that more work is required to understand the physical mechanisms operating in different regions of the parameter space, and for different boundary conditions

Comparative study of wall shear stress at the ascending aorta for different mechanical heart valve prostheses

An experimental study is reported which investigates the wall shear stress (WSS) distribution in a transparent model of the human aorta comparing a bileaflet mechanical heart valve (BMHV) with a trileaflet mechanical heart valve (TMHV) in physiological pulsatile flow. Elastic micro-pillar WSS sensors, calibrated by micro-Particle-Image-Velocimetry measurement, are applied to the wall along the ascending aorta. Peak WSS values are observed almost twice in BMHV compared to TMHV. Flow field analyses illuminate that these peaks are linked to the jet-like flows generated in the valves interacting with the aortic wall. Not only the magnitude but also the impact regions are specific for the different valve designs. The side-orifice jets generated by BMHV travel along the aortic wall in the ascending aorta and cause a whole range impact, while the jets generated by TMHV impact further downstream in the ascending aortic generating less severe WSS

Doctor of Philosophy

dissertationImage-based biomechanics, particularly numerical modeling using subject-specific data obtained via imaging, has proven useful for elucidating several biomechanical processes, such as prediction of deformation due to external loads, applicable to both normal function and pathophysiology of various organs. As the field evolves towards applications that stretch the limits of imaging hardware and acquisition time, the information traditionally expected as input for numerical routines often becomes incomplete or ambiguous, and requires specific acquisition and processing strategies to ensure physical accuracy and compatibility with predictive mathematical modeling. These strategies, often derivatives or specializations of traditional mechanics, effectively extend the nominal capability of medical imaging hardware providing subject-specific information coupled with the option of using the results for predictive numerical simulations. This research deals with the development of tools for extracting mechanical measurements from a finite set of imaging data and finite element analysis in the context of constructing structural atlases of the heart, understanding the biomechanics of the venous vasculature, and right ventricular failure. The tools include: (1) application of Hyperelastic Warping image registration to displacement-encoded MRI for reconstructing absolute displacement fields, (2) combination of imaging and a material parameter identification approach to measure morphology, deformation, and mechanical properties of vascular tissue, and (3) extrapolation of diffusion tensor MRI acquired at a single time point for the prediction the structural changes across the cardiac cycle with mechanical simulations. Selected tools were then applied to evaluate structural changes in a reversible animal model for right ventricular failure due to pressure overload

Stress and Strain Adaptation in Load-Dependent Remodeling of the Embryonic Left Ventricle

Altered pressure in the developing left ventricle (LV) results in altered morphology and tissue material properties. Mechanical stress and strain may play a role in the regulating process. This study showed that confocal microscopy, three-dimensional reconstruction, and finite element analysis can provide a detailed model of stress and strain in the trabeculated embryonic heart. The method was used to test the hypothesis that end-diastolic strains are normalized after altered loading of the LV during the stages of trabecular compaction and chamber formation. Stage-29 chick LVs subjected to pressure overload and underload at stage 21 were reconstructed with full trabecular morphology from confocal images and analyzed with finite element techniques. Measured material properties and intraventricular pressures were specified in the models. The results show volume-weighted end-diastolic von Mises stress and strain averaging 50–82% higher in the trabecular tissue than in the compact wall. The volume-weighted-average stresses for the entire LV were 115, 64, and 147Pa in control, underloaded, and overloaded models, while strains were 11, 7, and 4%; thus, neither was normalized in a volume-weighted sense. Localized epicardial strains at mid-longitudinal level were similar among the three groups and to strains measured from high-resolution ultrasound images. Sensitivity analysis showed changes in material properties are more significant than changes in geometry in the overloaded strain adaptation, although resulting stress was similar in both types of adaptation. These results emphasize the importance of appropriate metrics and the role of trabecular tissue in evaluating the evolution of stress and strain in relation to pressure-induced adaptation

A multiscale model for collagen alignment in wound healing

It is thought that collagen alignment plays a significant part in scar tissue formation during dermal wound healing. We present a multiscale model for collagen deposition and alignment during this process. We consider fibroblasts as discrete units moving within an extracellular matrix of collagen and fibrin modelled as continua. Our model includes flux induced alignment of collagen by fibroblasts, and contact guidance of fibroblasts by collagen fibres. We can use the model to predict the effects of certain manipulations, such as varying fibroblast speed, or placing an aligned piece of tissue in the wound. We also simulate experiments which alter the TGF-β concentrations in a healing dermal wound and use the model to offer an explanation of the observed influence of this growth factor on scarring