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Title: Modelling the mechanobiological evolution of aneurysms : an integrative in vivo, in vitro and in silico approach
Author: Mandaltsi, Aikaterini
ISNI:       0000 0004 6496 6701
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2016
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In silico models of intracranial aneurysm (IA) evolution aim to reliably represent the mechanical blood flow environment, the biology of the arterial wall and, crucially, the complex link between the two, namely the mechanobiology of healthy and diseased arteries. The ultimate goal is to create diagnostic tools for personalized management and treatment of aneurysm disease. Towards that target, the work presented in this thesis aims to establish a directly interactive link between experimental (in vivo and in vitro) and computational work for biologically and clinically relevant research on aneurysm disease. Mechanobiological hypotheses were firstly investigated in a novel 1D mathematical conceptual model of aneurysm evolution: for the first time these included representations of endothelial heterogeneity and smooth muscle cell (SMC) active stress response and apoptosis. The 1D investigations analysed and assessed the role of wall shear stress (WSS) homeostasis in elastin degradation, and the evolving role of the adventitia as a protective sheath in health and primary load-bearer in disease. The 1D framework was applied to a specific patient's aneurysm using both imaging and histological data to parameterise the model, calculating a material parameter for the adventitital collagen. The predicted evolution captured aspects of tissue changes measured with time focusing on the remodelled tissue wall thickness consistent with the experimental measurements, and physiological cyclic deformation in order to propose an approach to modelling adventitia's adaptive role to load bearing. Furthermore, an existing Fluid-Solid-Growth (FSG) computational framework was adapted and calibrated for the same patient-specific case with the help from the experimental data and the analysis from the 1D framework. This FSG model quantifies the arterial mechanical environment and captures the mechanical response of the fibrous arterial constituents. Comparing 1D and 3D investigations to establish consistency for our models, the 3Dmodel tested the hypothesis of WSS homeostasis, additionally introducing the element of spatial heterogeneity in the definition, and a new hypothesis linking cyclic deformation with collagen growth that ensures a physiological mechanical environment in stabilised aneurysms. Moreover, the FSG framework was applied in a specific rabbit aneurysm case and extended to link growth and remodeling to the detailed representation of the pulsatile blood flow mechanical environment. This research illustrates the power of computational modelling when coupled with rich data sets on the physiology, histology and geometry of healthy and diseased vascular tissue. In particular, the integrative modelling framework provides the foundation for establishing mechanobiological links crucial to aneurysm progression, and a basis for further research towards creating reliable aneurysm clinical tools.
Supervisor: Watton, Paul N. ; Thompson, Mark S. Sponsor: RCUK Digital Economy Programme
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biomechanical Engineering ; Computational Fluid Dynamics ; Vascular biomechanics ; Mechanobiology ; Aneurysm