Improving Understanding of Long-Term Cardiac Functional Remodelling via Cross-Sectional Analysis of Polyaffine Motion Parameters

International audienceChanges in cardiac motion dynamics occur as a direct result of alterations in structure, hemodynamics, and electrical activation. Abnormal ventricular motion compromises long-term sustainability of heart function. While motion abnormalities are reasonably well documented and have been identified for many conditions, the remodelling process that occurs as a condition progresses is not well understood. Thanks to the recent development of a method to quantify full ventricular motion (as opposed to 1D abstractions of the motion) with few comparable parameters, population-based statistical analysis is possible. A method for describing functional remodelling is proposed by performing statistical cross-sectional analysis of spatio-temporally aligned subject-specific polyaffine motion parameters. The proposed method is applied to pathological and control datasets to compare functional remodelling occurring as a process of disease as opposed to a process of ageing

A Novel Composite Material-based Computational Model for Left Ventricle Biomechanics Simulation

To model cardiac mechanics effectively, various mechanical characteristics of cardiac muscle tissue including anisotropy, hyperelasticity, and tissue active contraction characteristics must be considered. Some of these features cannot be implemented using commercial finite element (FE) solvers unless additional custom-developed computer codes/subroutines are appended. Such codes/subroutines are unavailable for the research community. Accordingly, the overarching objective of this research is to develop a novel LV mechanics model which is implementable in commercial FE solvers and can be used effectively within inverse FE frameworks towards cardiac disease diagnosis and therapy. This was broken down into a number of objectives. The first objective is to develop a novel cardiac tissue mechanical model. This model was constructed of microstructural cardiac tissue constituents while their associated volume contributions and mechanical properties were incorporated into the model. These constituents were organized in small FE tissue specimen models consistent with the normal/pathological cardiac tissue microstructure. In silico biaxial/uniaxial mechanical tests were conducted on the specimen models and corresponding stress-strain data were validated by comparing them with cardiac tissue data reported in the literature. Another objective of this research is developing a novel FE-based mechanical model of the LV which is fully implementable using commercial FE solvers without requiring further coding, potentially leading to a computationally efficient model which is easily adaptable to diverse pathological conditions. This was achieved through considering a novel composite material model of the cardiac tissue while all aspects of the cardiac mechanics including hyperelasticity, anisotropy, and active tissue responses were preserved. The model was applied to an in silico geometry of a canine LV under both normal and pathological conditions and systolic/diastolic responses of the model were compared with corresponding data of other LV mechanical models and LV contraction measurements. To test the suitability of the proposed cardiac model for FE inversion-based algorithms, the model was utilized for LV diastolic mechanical simulation to estimate the tissue stiffness and blood pressure using an ad-hoc optimization scheme. This led to reasonable tissue stiffness and blood pressure values falling within the range of LV measurements of healthy subjects, confirming the efficacy of this model for inversion-based diagnosis applications

A continuum treatment of growth in biological tissue: The coupling of mass transport and mechanics

Growth (and resorption) of biological tissue is formulated in the continuum setting. The treatment is macroscopic, rather than cellular or sub-cellular. Certain assumptions that are central to classical continuum mechanics are revisited, the theory is reformulated, and consequences for balance laws and constitutive relations are deduced. The treatment incorporates multiple species. Sources and fluxes of mass, and terms for momentum and energy transfer between species are introduced to enhance the classical balance laws. The transported species include: (\romannumeral 1) a fluid phase, and (\romannumeral 2) the precursors and byproducts of the reactions that create and break down tissue. A notable feature is that the full extent of coupling between mass transport and mechanics emerges from the thermodynamics. Contributions to fluxes from the concentration gradient, chemical potential gradient, stress gradient, body force and inertia have not emerged in a unified fashion from previous formulations of the problem. The present work demonstrates these effects via a physically-consistent treatment. The presence of multiple, interacting species requires that the formulation be consistent with mixture theory. This requirement has far-reaching consequences. A preliminary numerical example is included to demonstrate some aspects of the coupled formulation.Comment: 29 pages, 11 figures, accepted for publication in Journal of the Mechanics and Physics of Solids. See journal for final versio

Statistical analysis of organs' shapes and deformations: the Riemannian and the affine settings in computational anatomy

International audienceComputational anatomy is an emerging discipline at the interface of geometry, statistics and medicine that aims at analyzing and modeling the biological variability of organs' shapes at the population level. Shapes are equivalence classes of images, surfaces or deformations of a template under rigid body (or more general) transformations. Thus, they belong to non-linear manifolds. In order to deal with multiple samples in non-linear spaces, a consistent statistical framework on Riemannian manifolds has been designed over the last decade. We detail in this chapter the extension of this framework to Lie groups endowed with the affine symmetric connection, a more invariant (and thus more consistent) but non-metric structure on transformation groups. This theory provides strong theoretical bases for the use of one-parameter subgroups and diffeomorphisms parametrized by stationary velocity fields (SVF), for which efficient image registration methods like log-Demons have been developed with a great success from the practical point of view. One can further reduce the complexity with locally affine transformations , leading to parametric diffeomorphisms of low dimension encoding the major shape variability. We illustrate the methodology with the modeling of the evolution of the brain with Alzheimer's disease and the analysis of the cardiac motion from MRI sequences of images

PIV-based Investigation of Hemodynamic Factors in Diseased Carotid Artery Bifurcations with Varying Plaque Geometries

Ischemic stroke is often a consequence of complications due to clot formation (i.e. thrombosis) at the site of an atherosclerotic plaque developed in the internal carotid artery. Hemodynamic factors, such as shear-stress forces and flow disturbances, can facilitate the key mechanisms of thrombosis. Atherosclerotic plaques can differ in the severity of stenosis (narrowing), in eccentricity (symmetry), as well as inclusion of ulceration (wall roughness). Therefore, in terms of clinical significance, it is important to investigate how the local hemodynamics of the carotid artery is mediated by the geometry of plaque. Knowledge of thrombosis-associated hemodynamics may provide a basis to introduce advanced clinical diagnostic indices that reflect the increased probability of thrombosis and thus assist with better estimation of stroke risk, which is otherwise primarily assessed based on the degree of narrowing of the lumen. A stereoscopic particle image velocimetry (stereo-PIV) system was configured to obtain instantaneous full-field velocity measurements in life-sized carotid artery models. Extraction of the central-plane and volumetric features of the flow revealed the complexity of the stenotic carotid flow, which increased with increasing stenosis severity and changed with the symmetry of the plaque. Evaluation of the energy content of two models of the stenosed carotid bifurcation provided insight on the expected level of flow instabilities with potential clinical implications. Studies in a comprehensive family of eight models ranging from disease-free to severely stenosed (30%, 50%, 70% diameter reduction) and with two types of plaque symmetry (concentric or eccentric), as well as a single ulcerated stenosed model, clearly demonstrated the significance of plaque geometry in marked alteration of the levels and patterns of downstream flow disturbances and shear stress. Plaque eccentricity and ulceration resulted in enhanced flow disturbances. In addition, shear-stress patterns in those models with eccentric stenosis were suggestive of increased thrombosis potential at the post-stenotic recirculation zone compared to their concentric counterpart plaques

Investigation of Flow Disturbances and Multi-Directional Wall Shear Stress in the Stenosed Carotid Artery Bifurcation Using Particle Image Velocimetry

Hemodynamics and shear forces are associated with pathological changes in the vascular wall and its function, resulting in the focal development of atherosclerosis. Flow complexities that develop in the presence of established plaques create environments favourable to thrombosis formation and potentially plaque rupture leading to stroke. The carotid artery bifurcation is a common site of atherosclerosis development. Recently, the multi-directional nature of shear stress acting on the endothelial layer has been highlighted as a risk factor for atherogenesis, emphasizing the need for accurate measurements of shear stress magnitude as well direction. In the absence of comprehensive patient specific datasets numerical simulations of hemodynamics are limited by modeling assumptions. The objective of this thesis was to investigate the relative contributions of various factors - including geometry, rheology, pulsatility, and compliance – towards the development of disturbed flow and multi-directional wall shear stress (WSS) parameters related to the development of atherosclerosis An experimental stereoscopic particle image velocimetry (PIV) system was used to measure instantaneous full-field velocity in idealized asymmetrically stenosed carotid artery bifurcation models, enabling the extraction of bulk flow features and turbulence intensity (TI). The velocity data was combined with wall location information segmented from micro computed tomography (CT) to obtain phase-averaged maps of WSS magnitude and direction. A comparison between Newtonian and non-Newtonian blood-analogue fluids demonstrated that the conventional Newtonian viscosity assumption underestimates WSS magnitude while overestimating TI. Studies incorporating varying waveform pulsatility demonstrated that the levels of TI and oscillatory shear index (OSI) depend on the waveform amplitude in addition to the degree of vessel constriction. Local compliance resulted in a dampening of disturbed flow due to volumetric capacity of the upstream vessel, however wall tracking had a negligible effect on WSS prediction. While the degree of stenosis severity was found to have a dominant effect on local hemodynamics, comparable relative differences in metrics of flow and WSS disturbances were found due to viscosity model, waveform pulsatility and local vessel compliance

Bridging spatiotemporal scales in biomechanical models for living tissues : from the contracting Esophagus to cardiac growth

Appropriate functioning of our body is determined by the mechanical behavior of our organs. An improved understanding of the biomechanical functioning of the soft tissues making up these organs is therefore crucial for the choice for, and development of, efficient clinical treatment strategies focused on patient-specific pathophysiology. This doctoral dissertation describes the passive and active biomechanical behavior of gastrointestinal and cardiovascular tissue, both in the short and long term, through computer models that bridge the cell, tissue and organ scale. Using histological characterization, mechanical testing and medical imaging techniques, virtual esophagus and heart models are developed that simulate the patient-specific biomechanical organ behavior as accurately as possible. In addition to the diagnostic value of these models, the developed modeling technology also allows us to predict the acute and chronic effect of various treatment techniques, through e.g. drugs, surgery and/or medical equipment. Consequently, this dissertation offers insights that will have an unmistakable impact on the personalized medicine of the future.Het correct functioneren van ons lichaam wordt bepaald door het mechanisch gedrag van onze organen. Een verbeterd inzicht in het biomechanisch functioneren van deze zachte weefsels is daarom van cruciale waarde voor de keuze voor, en ontwikkeling van, efficiënte klinische behandelingsstrategieën gefocust op de patiënt-specifieke pathofysiologie. Deze doctoraatsthesis brengt het passieve en actieve biomechanisch gedrag van gastro-intestinaal en cardiovasculair weefsel, zowel op korte als lange termijn, in kaart via computermodellen die een brug vormen tussen cel-, weefsel- en orgaanniveau. Aan de hand van histologische karakterisering, mechanische testen en medische beeldvormingstechnieken worden virtuele slokdarm- en hartmodellen ontwikkeld die het patiënt-specifieke orgaangedrag zo accuraat mogelijk simuleren. Naast de diagnostische waarde van deze modellen, laat de ontwikkelde modelleringstechnologie ook toe om het effect van verschillende behandelingstechnieken, via medicatie, chirurgie en/of medische apparatuur bijvoorbeeld, acuut en chronisch te voorspellen. Bijgevolg biedt deze doctoraatsthesis inzichten die een onmiskenbare impact zullen hebben op de gepersonaliseerde geneeskunde van de toekomst