Application of smooth particle hydrodynamics method for modelling blood flow with thrombus formation

Thrombosis plays a crucial role in atherosclerosis or in haemostasis when a blood vessel is injured. This article focuses on using a meshless particle-based Lagrangian numerical technique, the smoothed particles hydrodynamic (SPH) method, to study the flow behaviour of blood and to explore the flow parameters that induce formation of a thrombus in a blood vessel. Due to its simplicity and effectiveness, the SPH method is employed here to simulate the process of thrombogenesis and to study the effect of various blood flow parameters. In the present SPH simulation, blood is modelled by two sets of particles that have the characteristics of plasma and of platelet, respectively. To simulate coagulation of platelets which leads to a thrombus, the so-called adhesion and aggregation mechanisms of the platelets during this process are modelled by an inter-particle force model. The transport of platelets in the flowing blood, platelet adhesion and aggregation processes are coupled with viscous blood flow for various low Reynolds number scenarios. The numerical results are compared with the experimental observations and a good agreement is found between the simulated and experimental results

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

Analysis of Blood Flow in Patient-specific Models of Type B Aortic Dissection

Aortic dissection is the most common acute catastrophic event affecting the aorta. The majority of patients presenting with an uncomplicated type B dissection are treated medically, but 25% of these patients develop subsequent dilatation and aortic aneurysm formation. The reasons behind the long‐term outcomes of type B aortic dissection are poorly understood. As haemodynamic factors have been involved in the development and progression of a variety of cardiovascular diseases, the flow phenomena and environment in patient‐specific models of type B aortic dissection have been studied in this thesis by applying computational fluid dynamics (CFD) to in vivo data. The present study aims to gain more detailed knowledge of the links between morphology, flow characteristics and clinical outcomes in type B dissection patients. The thesis includes two parts of patient‐specific study: a multiple case cross‐sectional study and a single case longitudinal study. The multiple cases study involved a group of ten patients with classic type B aortic dissection with a focus on examining the flow characteristics as well as the role of morphological factors in determining the flow patterns and haemodynamic parameters. The single case study was based on a series of follow‐up scans of a patient who has a stable dissection, with an aim to identify the specified haemodynamic factors that are associated with the progression of aortic dissection. Both studies were carried out based on computed tomography images acquired from the patients. 4D Phase‐contrast magnetic resonance imaging was performed on a typical type B aortic dissection patient to provide detailed flow data for validation purpose. This was achieved by qualitative and quantitative comparisons of velocity‐encoded images with simulation results of the CFD model. The analysis of simulation results, including velocity, wall shear stress and turbulence intensity profiles, demonstrates certain correlations between the morphological features and haemodynamic factors, and also their effects on long‐term outcomes of type B aortic dissections. The simulation results were in good agreement with in vivo MR flow data in the patient‐specific validation case, giving credence to the application of the computational model to the study of flow conditions in aortic dissection. This study made an important contribution by identifying the role of certain morphological and haemodynamic factors in the development of type B aortic dissection, which may help provide a better guideline to assist surgeons in choosing optimal treatment protocol for individual patient

Fluid Dynamic Modeling of Biological Fluids: From the Cerebrospinal Fluid to Blood Thrombosis

1noL'abstract è presente nell'allegato / the abstract is in the attachmentopen718. INGEGNERIA CIVILE E AMBIENTALEnoopenCardillo, Giuli

In-silico clinical trials for assessment of intracranial flow diverters

In-silico trials refer to pre-clinical trials performed, entirely or in part, using individualised computer models that simulate some aspect of drug effect, medical device, or clinical intervention. Such virtual trials reduce and optimise animal and clinical trials, and enable exploring a wider range of anatomies and physiologies. In the context of endovascular treatment of intracranial aneurysms, in-silico trials can be used to evaluate the effectiveness of endovascular devices over virtual populations of patients with different aneurysm morphologies and physiologies. However, this requires (i) a virtual endovascular treatment model to evaluate device performance based on a reliable performance indicator, (ii) models that represent intra- and inter-subject variations of a virtual population, and (iii) creation of cost-effective and fully-automatic workflows to enable a large number of simulations at a reasonable computational cost and time. Flow-diverting stents have been proven safe and effective in the treatment of large wide-necked intracranial aneurysms. The presented thesis aims to provide the ingredient models of a workflow for in-silico trials of flow-diverting stents and to enhance the general knowledge of how the ingredient models can be streamlined and accelerated to allow large-scale trials. This work contributed to the following aspects: 1) To understand the key ingredient models of a virtual treatment workflow for evaluation of the flow-diverter performance. 2) To understand the effect of input uncertainty and variability on the workflow outputs, 3) To develop generative statistical models that describe variability in internal carotid artery flow waveforms, and investigate the effect of uncertainties on quantification of aneurysmal wall shear stress, 4) As part of a metric to evaluate success of flow diversion, to develop and validate a thrombosis model to assess FD-induced clot stability, and 5) To understand how a fully-automatic aneurysm flow modelling workflow can be built and how computationally inexpensive models can reduce the computational costs

Evolution of the wall shear stresses during the progressive enlargement of symmetric abdominal aortic aneurysms.

The changes in the evolution of the spatial and temporal distribution of the wall shear stresses (WSS) and gradients of wall shear stresses (GWSS) at different stages of the enlargement of an abdominal aortic aneurysm (AAA) are important in understanding the aetiology and progression of this vascular disease since they affect the wall structural integrity, primarily via the changes induced on the shape, functions and metabolism of the endothelial cells. Particle image velocimetry (PIV) measurements were performed in in vitro aneurysm models, while changing their geometric parameters systematically. It has been shown that, even at the very early stages of the disease, i.e. increase in the diameter ≤ 50%, the flow separates from the wall and a large vortex ring, usually followed by internal shear layers, is created. These lead to the generation of WSS that drastically differ in mean and fluctuating components from the healthy vessel. Inside the AAA, the mean WSS becomes negative along most of the aneurysmal wall and the magnitude of the WSS can be as low as 26% of the value in a healthy abdominal aorta. Two regions with distinct patterns of WSS were identified inside the AAA: the proximal region of flow detachment, characterized by oscillatory WSS of very low mean, and the region of flow reattachment, located distally, where large, negative WSS and sustained GWSS are produced as a result of the impact of the vortex ring on the wall. Comparison of the measured values of WSS and GWSS to an analytical solution, calculated for slowly expanding aneurysms shows a very good agreement, thus providing a validation of the PIV measurements

Hypoxic Cell Waves around Necrotic Cores in Glioblastoma: A Biomathematical Model and its Therapeutic Implications

Glioblastoma is a rapidly evolving high-grade astrocytoma that is distinguished pathologically from lower grade gliomas by the presence of necrosis and microvascular hiperplasia. Necrotic areas are typically surrounded by hypercellular regions known as "pseudopalisades" originated by local tumor vessel occlusions that induce collective cellular migration events. This leads to the formation of waves of tumor cells actively migrating away from central hypoxia. We present a mathematical model that incorporates the interplay among two tumor cell phenotypes, a necrotic core and the oxygen distribution. Our simulations reveal the formation of a traveling wave of tumor cells that reproduces the observed histologic patterns of pseudopalisades. Additional simulations of the model equations show that preventing the collapse of tumor microvessels leads to slower glioma invasion, a fact that might be exploited for therapeutic purposes.Comment: 29 pages, 9 figure

Application of Numerical Simulation in Cardiovascular Medicine

Introduction: The purpose of this thesis is to study atherosclerotic risk and thrombotic risk through application of numerical simulation to cardiovascular geometry and morphology. This has been applied to two specific situations, the angle of take-off of the left main coronary artery and the morphology of the left atrial appendage. A. The distribution of atherosclerotic plaque and the plaque rupture rate in isolated left main coronary disease is different to that seen in left main disease with multi-vessel disease, suggesting local biomechanical forces play an important part in governing plaque formation and rupture. The varying vertical left main coronary artery take-off angulation may impact on the wall shear stress. B. Different left atrial appendage morphologies seem to have different risk of thromboembolism, in patients with atrial fibrillation and low CHADS2 VASC score. From this observation, it can be hypothesized that left atrial morphology subtype with a more complex structure can lead to higher volume of blood stagnation. Aim: A. To investigate the effects of vertical take-off angulation of the left main coronary artery from aorta and varying stenosis severities on wall shear stress in the left main coronary artery. B. To investigate the impact of different left atrial appendage morphologies on slow vortical flow estimated by flow dynamics. Methods: A. Artificially created and patient-specific computed tomography-derived 3-dimensional digital models of the left main coronary artery with varying vertical take-off angulation and artery stenoses were generated. These were exported for numerical simulation to calculate the wall shear stress values and mapping in each model set. B. Patient-specific computed tomography-derived 3-dimensional digital model sets of different left atrial appendage morphologies were exported for numerical simulation to calculate the volume and distribution of slow vortical flow. Left atrial appendage emptying was assessed. Results: A. The study of left main take off demonstrated that the preferred development site of atherosclerotic plaques in pathological studies corresponds to regions of low wall shear stress. Both peak wall shear stress and mean wall shear stress increased with more vertical take-off, and this relationship was accentuated by increasing stenosis severity. The more vertically angled LMCA take-off from aorta in the presence of significant stenosis severity was also associated with a larger area of low wall shear stress. These findings may explain the higher atherosclerotic plaque rupture rate and higher percentage of proximally located plaque seen in isolated left main coronary artery disease B. For complex geometry, the Cauliflower left atrial appendage subtype contained the greatest volume of slow vortical flow at low shear rate across a range of different left atrial appendage emptying velocities. This rheological mechanistic observation correlates well with the clinical observation that the highest rate of clinical thromboembolism is seen with the Cauliflower subtype in patients with low CHADS2 VASC score atrial fibrillation. However, in the presence of severely depressed left atrial appendage function differences between left atrial appendage morphology subtypes diminish. Conclusion: A. LMCA angulation may be an additional important factor to be considered in the clinical evaluation of the pathogenesis and progression of LMCA atheromatous disease. B. Stasis of blood, assessed in this study by the volume of slow vortical flow, is shown to depend on left atrial appendage morphology, and also depends on left atrial appendage function/emptying velocity. Under conditions when function is mildly to moderately reduced, then it is likely that morphology is an important variable