Assessing the Near-Wall Hemodynamics in the Left Coronary Artery Using CFD

The objective of this thesis is to computationally investigate the flow mechanics and the near-wall hemodynamics associated with the different take-off angles in the left coronary artery of the human heart. From this study, we will be able to evaluate if the increase in the take-off angles of the left coronary artery will significantly increases or decrease the likelihood of plaque (atherosclerosis) buildup in the left coronary artery bifurcations. This study quantifies the effects of the varying take-off angles on the branches along the left anterior descending (LAD) of the left coronary artery using computational fluid dynamics (CFD) simulations. The study aims to compare five test cases of the different take off-angles of the left coronary artery (LCA) and four different branch angles between the LAD and the left circumflex (LCx). It also considered the branch angles of the coronary artery downstream the LAD. The idealized geometries used for this study were constructed in SolidWorks 2015 and imported as surface meshes into Star-CCM+, a commercially available CFD solver. In this study, the LCA inlet boundary conditions was set as a pulsatile mass flow inlet and flow split ratios were set for the outlets boundary conditions that are representations of a middle age man at rest. The nature of blood pulsatile flow characteristic was accounted for and the properties of blood which include the density (1,050Kg/m3) and dynamic viscosity (0.0046Pa) were obtained from previous research. The results from the simulations are compared using established scales for the parameters evaluated. The parameters evaluated were: (i) Oscillatory Shear Index (OSI); which quantifies the extent in which the blood flow changes direction as it flows (ii) Time Average Wall Shear Stress (TAWSS); which quantifies the average shear stress experienced by the wall of the artery and (ii) Relative Residence Time (RRT); which defined how long blood spends in a location during blood flow. These parameters are used to predict the likelihood of blood clots, atherosclerosis, endothelial damage, plaque formation, and aneurysm in the blood vessels. The data from the simulations were analyzed using functional macros to quantify and generate threshold values for the parameters. Computational Fluid Dynamics has gain more recognition in field of medicine because it has been used to obtain the various mechanic behaviors of most artificial implanted devices used for endovascular and cardiovascular treatments before these devices are used in patients’ treatment. This can be a useful insight in coronary stenting, solid and stress analysis of biodegradable stent and can also provide insight into stenting for more complex arterial networks like brain stent grafts. In addition, it is important to understand the hemodynamics of the LCA before carrying out stent graft or angioplasty procedures. This will help determine the effectiveness of the stent graft in the coronary artery

Transient Cardiovascular Hemodynamics In A Patient-Specific Arterial System

The ultimate goal of the present study is to aid in the development of tools to assist in the treatment of cardiovascular disease. Gaining an understanding of hemodynamic parameters for medical implants allow clinicians to have some patient-specific proposals for intervention planning. In the present study a full cardiovascular experimental phantom and digital phantom (CFD model) was fabricated to study: (1) the effects of local hemodynamics on global hemodynamics, (2) the effects of transition from bed-rest to upright position, and (3) transport of dye (drug delivery) in the arterial system. Computational three dimensional (3-D) models (designs A, B, and C) stents were also developed to study the effects of stent design on hemodynamic flow and the effects of drug deposition into the arterial wall. The experimental phantom used in the present study is the first system reported in literature to be used for hemodynamic assessment in static and orthostatic posture changes. Both the digital and experimental phantom proved to provide different magnitudes of wall shear and normal stresses in sections where previous studies have only analyzed single arteries. The dye mass concentration study for the digital and experimental cardiovascular phantom proved to be useful as a surrogate for medical drug dispersion. The dye mass concentration provided information such as transition time and drug trajectory paths. For the stent design CFD studies, hemodynamic results (wall shear stress (WSS), normal stress, and vorticity) were assessed to determine if simplified stented geometries can be used as a surrogate for patient-specific geometries and the role of stent design on flow. Substantial differences in hemodynamic parameters were found to exist which confirms the need for patient-specific modeling. For drug eluting stent studies, the total deposition time for the drug into the arterial wall was approximately 3.5 months

Hemodynamics and Endothelial Cell Biology in Cardiovascular Diseases

Atherosclerotic plaques develop preferentially in curved and branching arteries in-vivo. Lipids and inflammatory cells accumulation in the intimal layer of the arterial wall is considered as the main driving mechanism in the disease progression. Evidences suggest that this focal distribution of plaques may result from the combination of systemic risk factors including high plasma cholesterol, smoking, diabetis, hypertension or genetic pre-disposition and local hemodynamic risk factors such as low and oscillatory flows. The exact mechanism of the biological and biomechanical interactions between the endothelium, blood flow and the growing lesion underneath still remains unclear. This thesis is a study on the relationship between biomechanical factors found in proatherogenic flow and endothelial inflammation. The thesis focuses in particular on the effect of secondary flows on wall shear stress and mass transport distribution. To that end, we have combined different techniques from flow imaging, 3D flow reconstruction, vascular biology and mathematical simulation of biological network. In particular, shear stress is involved in the regulation of the pro-inflammatory transcription factor nuclear factor -kB (NF-kB) and the vasoregulator Nitric Oxide. The role of endothelial Nitric Oxide and wall shear stress on NF-kB activation is still controversial. We investigated here the hypothesis that NO negatively regulates NF- kB activation in flow chamber with sheared endothelial cells and using a mathematical model of the NF-kB-NO pathway. Understanding the underlying relationship between hemodynamic factors and inflammatory cells transport to the wall may contribute to the development of better therapies or interventional practices to treat patients with atherosclerotic diseases

Plaque Rupture Prediction in Human Arteries

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