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    Plaque Rupture Prediction in Human Arteries

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    According to the World Health Organisation (WHO), coronary artery disease (CAD) and stroke are the two leading causes of death globally, with more than 15.2 million deaths in 2016. In 2017, there were: 18,000 and 10,000 deaths in Australia due to CAD and cerebrovascular diseases, respectively. Atherosclerosis is the predominant cause for both coronary and cerebrovascular diseases with acute events usually caused by plaque rupture which releases thrombogenic material into the artery lumen leading to clot formation. Identification of the most at risk plaques for rupture, known as the ‘vulnerable plaque’, remains an important pursuit in the treatment of patients with CAD. The aim of this thesis was to model and simulate the nonlinear fluidstructure interaction (FSI) dynamics of atherosclerotic coronary arteries, based on clinical data, as a tool to recognise vulnerable locations and hence to predict the initiation of heart attack. This thesis consists of four peerreviewed journal papers, two published and two submitted for publication. • Paper 1: A dynamic, three-dimensional (3D), visco/hyperelastic, FSI model of an atherosclerotic coronary artery was developed via the finite element method (FEM) to examine the risk of high shear/von Mises stresses, incorporating: physiological pulsatile blood flow; tapered shape of the artery; viscoelasticity and hyperelasticity of the artery wall; effect of the motion of the heart; active artery muscle contraction; the lipid core inside the plaque; three layers of the artery wall; non-Newtonian characteristics of the blood flow; and micro-calcification. The paper has been published in the International Journal of Engineering Science (Q1; Impact Factor = 9.052; journal rank: 1 out of 88 in Multidisciplinary Engineering). • Paper 2: One of the highest risk locations of plaque growth and rupture initiation and hence occurrence of heart attack is the first main bifurcation of the left main (LM) coronary artery. Hence, this investigation aimed to analyse the nonlinear, three-dimensional biomechanics of the bifurcated, atherosclerotic LM coronary artery. The artery tree was modelled using FSI incorporating three-dimensionality, nonlinear geometric and material properties, asymmetry, viscosity, and hyperelasticity. The paper has been published in the International Journal of Engineering Science (Q1; Impact Factor = 9.052; journal rank: 1 out of 88 in Multidisciplinary Engineering) • Paper 3: Clinical data measurement was conducted at the Royal Adelaide Hospital (RAH) for two patients who underwent in vivo coronary angiography, optical coherence tomography (OCT) imaging, and electrocardiography (ECG). These clinically measured data were analysed using image processing techniques to obtain realistic geometries of the coronary arteries, heart motion measurements, and corresponding heart rate characteristics. A 3D FSI model was then developed using FEM, based on the measured clinical data for determination of high-risk locations. Validation of the model/simulations with clinical data was also performed. • Paper 4: In vivo OCT, ECG, angiography, and time-dependent blood pressure measurements were conducted for a patient at the RAH and the obtained data were analysed using image processing techniques. Fatigue-life and crack-analysis FEM models were developed and simulations were performed based on clinical obtained data for crack propagation, fatigue crack growth and plaque life analyses.Thesis (Ph.D.) -- University of Adelaide, School of Mechanical Engineering, 201
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