Intimal and medial contributions to the hydraulic resistance of the arterial wall at different pressures: a combined computational and experimental study

The hydraulic resistances of the intima and media determine water flux and the advection of macromolecules into and across the arterial wall. Despite several experimental and computational studies, these transport processes and their dependence on transmural pressure remain incompletely understood. Here, we use a combination of experimental and computational methods to ascertain how the hydraulic permeability of the rat abdominal aorta depends on these two layers and how it is affected by structural rearrangement of the media under pressure. Ex vivo experiments determined the conductance of the whole wall, the thickness of the media and the geometry of medial smooth muscle cells (SMCs) and extracellular matrix (ECM). Numerical methods were used to compute water flux through the media. Intimal values were obtained by subtraction. A mechanism was identified that modulates pressure-induced changes in medial transport properties: compaction of the ECM leading to spatial reorganization of SMCs. This is summarized in an empirical constitutive law for permeability and volumetric strain. It led to the physiologically interesting observation that, as a consequence of the changes in medial microstructure, the relative contributions of the intima and media to the hydraulic resistance of the wall depend on the applied pressure; medial resistance dominated at pressures above approximately 93 mmHg in this vessel

ARTreat Project: Three-Dimensional Numerical Simulation of Plaque Formation and Development in the Arteries

Atherosclerosis is a progressive disease characterized by the accumulation of lipids and fibrous elements in arteries. It is characterized by dysfunction of endothelium and vasculitis, and accumulation of lipid, cholesterol, and cell elements inside blood vessel wall. In this study, a continuum-based approach for plaque formation and development in 3-D is presented. The blood flow is simulated by the 3-D Navier-Stokes equations, together with the continuity equation while low-density lipoprotein (LDL) transport in lumen of the vessel is coupled with Kedem-Katchalsky equations. The inflammatory process was solved using three additional reaction-diffusion partial differential equations. Transport of labeled LDL was fitted with our experiment on the rabbit animal model. Matching with histological data for LDL localization was achieved. Also, 3-D model of the straight artery with initial mild constriction of 30% plaque for formation and development is presented

Mathematical modelling of mass transport in large arteries

Atherosclerosis is a major cause of morbidity and mortality in the western world. The focal depletion of oxygen and accumulation of macromolecules are believed to initiate, accelerate and complicate the development of atherosclerosis. However, species concentrations in vessel walls are difficult to measure in vivo non-invasively. Therefore, it is essential to obtain detailed concentration profiles of atherogenic molecules to gain further understanding of the mass transfer mechanisms within arterial walls. In the present study, comprehensive mathematical models describing species transport in large arteries are developed and presented. Existing mathematical models are reviewed and reconciled. A fluid phase model, a single-layered and a multilayered fluid-wall models are employed to simulate the mass transfer processes in proatherosclerotic arteries. Since trans-endothelial transport is considered to be an important sub-process in the system and is dependent on wall shear stress (WSS) imposed on the endothelial surface, shear-dependent transport properties are derived from relevant experimental data in the literature. A novel approach, which exploits the optimisation theory, is proposed and used to determine model parameters based on the experimental data. Furthermore, numerical schemes to accommodate the effects of pulsatile flow on lipid transport in the arterial wall are presented in the thesis. Mathematical models and numerical schemes are tested and compared using idealised computational geometries. Then the models are applied to realistic geometries to investigate: 1) oxygen transport in a normal human abdominal aorta and an abdominal aortic aneurysm (AAA) with intralumenal thrombus (ILT); 2) macromolecular transport in a mildly stenosed human right coronary artery (RCA). Based on the model predictions, mechanisms inducing hypoxia and macromolecular accumulation are discussed in depth

ARTreat Project: Three-Dimensional Numerical Simulation of Plaque Formation and Development in the Arteries

Atherosclerosis is a progressive disease characterized by the accumulation of lipids and fibrous elements in arteries. It is characterized by dysfunction of endothelium and vasculitis, and accumulation of lipid, cholesterol, and cell elements inside blood vessel wall. In this study, a continuum-based approach for plaque formation and development in 3-D is presented. The blood flow is simulated by the 3-D Navier-Stokes equations, together with the continuity equation while low-density lipoprotein (LDL) transport in lumen of the vessel is coupled with Kedem-Katchalsky equations. The inflammatory process was solved using three additional reaction-diffusion partial differential equations. Transport of labeled LDL was fitted with our experiment on the rabbit animal model. Matching with histological data for LDL localization was achieved. Also, 3-D model of the straight artery with initial mild constriction of 30% plaque for formation and development is presented

Haemodynamics analysis of carotid artery stenosis and carotid artery stenting

Carotid stenosis is a local narrowing of the carotid artery, and is usually found in the internal carotid artery. The presence of a high-degree stenosis in a carotid artery may provoke transition from laminar to turbulent flow during part of the cardiac cycle. Turbulence in blood flow can influence haemodynamic parameters such as velocity profiles, shear stress and pressure, which are important in wall remodelling. Patients with severe stenosis could be treated with a minimally invasive clinical procedure, carotid artery stenting (CAS). Although CAS has been widely adopted in clinical practice, the complication of in-stent restenosis (ISR) has been reported after CAS. The incidence of ISR is influenced by stent characteristics and vessel geometry, and correlates strongly with regions of neointimal hyperplasia (NH). Therefore, the main purpose of this study is to provide more insights into the haemodynamics in stenosed carotid artery and in post-CAS geometries via computational simulation. The first part of the thesis presents a computational study on flow features in a stenotic carotid artery bifurcation using two computational approaches, large eddy simulation (LES) and Reynolds-averaged Navier-Stokes (RANS) incorporating the Shear Stress Transport model with the γ-Reθ transition (SST-Tran) models. The computed flow patterns are compared with those measured with particle image velocimetry (PIV). The results show that both SST-Tran and LES can predict the PIV results reasonably well, but LES is more accurate especially at locations distal to the stenosis where flow is highly disturbed. The second part of the thesis is to determine how stent strut design may influence the development of ISR at the carotid artery bifurcation following CAS. Key parameters that can be indicative of ISR are obtained for different stent designs and compared; these include low and oscillating wall shear stress (WSS), high residence time, and wall stress. A computationally efficient methodology is employed to reproduce stent strut geometry. This method facilitates the accurate reconstruction of actual stent geometry and details of strut configuration and its inclusion in the fluid domain. Computational simulations for flow patterns and low-density lipoprotein (LDL) transport are carried out in order to investigate spatial and temporal variations of WSS and LDL accumulation in the stented carotid geometries. Furthermore, finite element (FE) analysis is performed to evaluate the wall stress distribution with different stent designs. The results reveal that the closed-cell stent design is more likely to create atheroprone and procoagulant flow conditions, causing larger area to be exposed to low wall shear stress (WSS), elevated oscillatory shear index, as well as to induce higher wall stress compared to the open-cell stent design. This study also demonstrates the suitability of SST-Tran and LES models in capturing the presence of complex flow patterns in post-stenotic region.Open Acces

The Effects of Time Varying Curvature on Species Transport in Coronary Arteries

Alterations in mass transport patterns of low-density lipoproteins (LDL) and oxygen are known to cause atherosclerosis in larger arteries. We hypothesise that the species transport processes in coronary arteries may be affected by their physiological motion, a factor which has not been considered widely in mass transfer studies. Hence, we numerically simulated the mass transport of LDL and oxygen in an idealized moving coronary artery model under both steady and pulsatile flow conditions. A physiological inlet velocity and a sinusoidal curvature waveform were specified as velocity and wall motion boundary conditions. The results predicted elevation of LDL flux, impaired oxygen flux and low wall shear stress (WSS) along the inner wall of curvature, a predilection site for atherosclerosis. The wall motion induced changes in the velocity and WSS patterns were only secondary to the pulsatile flow effects. The temporal variations in flow and WSS due to the flow pulsation and wall motion did not affect temporal changes in the species wall flux. However, the wall motion did alter the time-averaged oxygen and LDL flux in the order of 26% and 12% respectively. Taken together, these results suggest that the wall motion may play an important role in coronary arterial transport processes and emphasise the need for further investigation