IMPACT OF HEMODYNAMIC VORTEX SPATIAL AND TEMPORAL CHARACTERISTICS ON ANALYSIS OF INTRACRANIAL ANEURYSMS

Subarachnoid hemorrhage is a potentially devastating pathological condition in which bleeding occurs into the space surrounding the brain. One of the prominent sources of subarachnoid hemorrhage are intracranial aneurysms (IA): degenerative, irregular expansions of area(s) of the cerebral vasculature. In the event of IA rupture, the resultant subarachnoid hemorrhage ends in patient mortality occurring in ~50% of cases, with survivors enduring significant neurological damage with physical or cognitive impairment. The seriousness of IA rupture drives a degree of clinical interest in understanding these conditions that promote both the development and possible rupture of the vascular malformations. Current metrics for the assessment of this pathology rely on measuring the geometric characteristics of a patient\u27s vessel and/or IA, as well as the hemodynamic stressors existing along the vessel wall. Comparatively less focus has been granted toward understanding the characteristics of much of the bulk-flow within the vasculature and how it may play a role in IAs. Specifically, swirling hemodynamic flow (vortices) have been suggested as a condition which exacerbates vascular changes leading to IAs, yet quantified measurements of the spatial and temporal characteristics of vortices remain overlooked. This dissertation studies the role of the spatial and temporal characteristics of vortex flow and how it plays a role on IA pathology. Its chapters are a collection of five (5) works into this matter. First, established methods for the identification of vortices was investigated, and a novel method for vortex identification and quantification of their characteristics was developed to overcome the limitations of previous methods. Second, the developed method for vortex identification/quantification was then applied to a simulation study to improve predictive models aimed at predicting areas of IA development from those unlikely to suffer this pathology. Third, assessing how the simulated repair of one IA impacts changes to hemodynamic conditions within other nearby un-repaired IAs in a multiple IA system. Fourth, it was determined if vortex identification/quantification improved predictive models aimed at differentiation ruptured from unruptured IAs. Fifth, impart vortical flow of differing characteristics onto cultured vascular cells to determine if vortex stability imparts varied levels of cellular changes

Effect of Newtonian and non-Newtonian flow in subject specific carotid artery

Advances in the numerical simulation techniques has immensely helped in the demonstrating the importance of blood flow through elastic arteries and evaluating the disease progression and flow dynamics of cardiovascular diseases such as atherosclerosis. The present work deals with a case study of a patient diagnosed with partial narrowing of entire cervical segment of Internal Carotid Artery (ICA), while Common Carotid Artery (CCA) and External Carotid Artery (ECA) appears to be normal. Subject specific 3D carotid bifurcation CAD model is generated based on CT-angio scan data using MIMICS-14.0 and numerical analysis is performed using Computational Fluid Dynamics (CFD) in ANSYS-CFX-14.0. Pulsatile blood flow through the subject-specific artery is investigated to study the influence of rheology on the haemodynamics in the blood flow. The simulation results obtained through Carreau-Yasuda and Newtonian models are investigated. Flow behaviour observed during peak systole exhibits significant difference in the spatial parameters between both the Newtonian and nonNewtonians models. The comparison of local shear stress magnitude in CCA, ICA and ECA demonstrates that WSS is highly influenced by the shear thinning property of blood. This variation is also observed artery branches with reduced lumen diameter, lumen narrowing due to stenosis and in the bifurcation zone

In Vitro and Computational Analyses of Blood Flow at Aortoiliac Bifurcation for Patients with Atherosclerotic Plaque Treated with Endovascular Procedures

This research has developed an appropriate approach allowing for more accurate assessment of haemodynamic changes following implantation of endovascular stent graft to treat patients with occlusive aortoiliac disease. Two different endovascular techniques involving the use of different types of stent grafts were analysed and compared with regard to haemodynamics associated with these techniques. Results improved understanding of the flow characteristics of these endovascular techniques

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

Computational Fluid Dynamics in Cardiovascular Disease

Computational fluid dynamics (CFD) is a mechanical engineering field for analyzing fluid flow, heat transfer, and associated phenomena, using computer-based simulation. CFD is a widely adopted methodology for solving complex problems in many modern engineering fields. The merit of CFD is developing new and improved devices and system designs, and optimization is conducted on existing equipment through computational simulations, resulting in enhanced efficiency and lower operating costs. However, in the biomedical field, CFD is still emerging. The main reason why CFD in the biomedical field has lagged behind is the tremendous complexity of human body fluid behavior. Recently, CFD biomedical research is more accessible, because high performance hardware and software are easily available with advances in computer science. All CFD processes contain three main components to provide useful information, such as pre-processing, solving mathematical equations, and post-processing. Initial accurate geometric modeling and boundary conditions are essential to achieve adequate results. Medical imaging, such as ultrasound imaging, computed tomography, and magnetic resonance imaging can be used for modeling, and Doppler ultrasound, pressure wire, and non-invasive pressure measurements are used for flow velocity and pressure as a boundary condition. Many simulations and clinical results have been used to study congenital heart disease, heart failure, ventricle function, aortic disease, and carotid and intra-cranial cerebrovascular diseases. With decreasing hardware costs and rapid computing times, researchers and medical scientists may increasingly use this reliable CFD tool to deliver accurate results. A realistic, multidisciplinary approach is essential to accomplish these tasks. Indefinite collaborations between mechanical engineers and clinical and medical scientists are essential. CFD may be an important methodology to understand the pathophysiology of the development and progression of disease and for establishing and creating treatment modalities in the cardiovascular field

Computational Fluid Dynamics in Cardiovascular Disease

Computational fluid dynamics (CFD) is a mechanical engineering field for analyzing fluid flow, heat transfer, and associated phenomena, using computer-based simulation. CFD is a widely adopted methodology for solving complex problems in many modern engineering fields. The merit of CFD is developing new and improved devices and system designs, and optimization is conducted on existing equipment through computational simulations, resulting in enhanced efficiency and lower operating costs. However, in the biomedical field, CFD is still emerging. The main reason why CFD in the biomedical field has lagged behind is the tremendous complexity of human body fluid behavior. Recently, CFD biomedical research is more accessible, because high performance hardware and software are easily available with advances in computer science. All CFD processes contain three main components to provide useful information, such as pre-processing, solving mathematical equations, and post-processing. Initial accurate geometric modeling and boundary conditions are essential to achieve adequate results. Medical imaging, such as ultrasound imaging, computed tomography, and magnetic resonance imaging can be used for modeling, and Doppler ultrasound, pressure wire, and non-invasive pressure measurements are used for flow velocity and pressure as a boundary condition. Many simulations and clinical results have been used to study congenital heart disease, heart failure, ventricle function, aortic disease, and carotid and intra-cranial cerebrovascular diseases. With decreasing hardware costs and rapid computing times, researchers and medical scientists may increasingly use this reliable CFD tool to deliver accurate results. A realistic, multidisciplinary approach is essential to accomplish these tasks. Indefinite collaborations between mechanical engineers and clinical and medical scientists are essential. CFD may be an important methodology to understand the pathophysiology of the development and progression of disease and for establishing and creating treatment modalities in the cardiovascular field

TURBULENCE ACCUMULATION AND AVERAGE IN THE SYMMETRICALLY AND ASYMMETRICALLY STENOSED CAROTID BIFURCATION

Ischemic stroke due to atherosclerotic disease has been studied widely in the recent past. Most studies focus on either the correlation between stroke risk and stenosis severity (narrowing of the plaque in the vessel) or mechanisms affecting platelet activation and aggregation. Shear stress has been identified as a strong indicator for platelet activation/aggregation, resulting in both thrombus formation and plaque growth. This has subsequently been correlated with regions of elevated turbulence. Doppler ultrasound offers a method of characterizing these flow disturbances using a well-established parameter—turbulence intensity (Tl), which is the root mean squared deviation in the spectral mean velocity. Using an in-house in vitro flow system, Doppler spectra are obtained at each of over 1000, 1-mm3 isotropically spaced sites in the central plane of seven Teflon phantoms simulating varying degrees of arterial disease. An average of Tl over a 25 mm2 region of interest, as well as the volume of Tl and the cumulative Tl over the internal carotid artery showed that downstream turbulence increased significantly with both stenosis severity (30% - 650% increase) and plaque asymmetry (10% - 30% increase)

Hemodynamics in the Stenosed Carotid Bifurcation with Plaque Ulceration

The presence of irregular plaque surface morphology or ulceration of the atherosclerotic lesion has been identified as an independent risk factor for ischemic stroke. Doppler ultrasound (DUS) is the most commonly performed non-invasive technique used to assess patients suspected of having carotid artery disease, but currently does not incorporate the diagnosis of plaque ulceration. Advanced Doppler analyses incorporating quantitative estimates of flow disturbances may result in diagnostic indices that identify plaque ulcerative conditions. A technique for the fabrication of DUS-compatible flow phantoms was developed, using a direct-machining method that is amenable to comprehensive DUS investigations. In vitro flow studies in an ensemble of matched model vessel geometries determined that ulceration as small as 2 mm can generate significant disturbances in the downstream flow field in a moderately stenosed carotid artery, which are detectable using the DUS velocity-derived parameter turbulence intensity (TI) measured with a clinical system. Further experimental results showed that distal TI was significantly elevated (P \u3c 0.001) due to proximal plaque ulceration in the mild and moderately stenosed carotid bifurcation (30%, 50%, 60% diameter reduction), and also increased with stenosis severity. Pulsatile computational fluid dynamics (CFD) models, with simulated particle tracking, demonstrated enhanced flow disruption of the stenotic jet and slight elevations in path-dependent shear exposure parameters in a stenosed carotid bifurcation model with ulceration. In addition, CFD models were used to evaluate the DUS index TI using finite volume sampling

Computational modeling of low-density lipoprotein accumulation at the carotid artery bifurcation after stenting

Restenosis typically occurs in regions of low and oscillating wall shear stress, which also favor the accumulation of atherogenic macromolecules such as low-density lipoprotein (LDL). This study aims to evaluate LDL transport and accumulation at the carotid artery bifurcation following carotid artery stenting (CAS) by means of computational simulation. The computational model consists of coupled blood flow and LDL transport, with the latter being modeled as a dilute substance dissolved in the blood and transported by the flow through a convection-diffusion transport equation. The endothelial layer was assumed to be permeable to LDL, and the hydraulic conductivity of LDL was shear-dependent. Anatomically realistic geometric models of the carotid bifurcation were built based on pre- and post-stent computed tomography (CT) scans. The influence of stent design was investigated by virtually deploying two different types of stents (open- and closed-cell stents) into the same carotid bifurcation model. Predicted LDL concentrations were compared between the post-stent carotid models and the relatively normal contralateral model reconstructed from patient-specific CT images. Our results show elevated LDL concentration in the distal section of the stent in all post-stent models, where LDL concentration is 20 times higher than that in the contralateral carotid. Compared with the open-cell stents, the closed-cell stents have larger areas exposed to high LDL concentration, suggesting an increased risk of stent restenosis. This computational approach is readily applicable to multiple patient studies and, once fully validated against follow-up data, it can help elucidate the role of stent strut design in the development of in-stent restenosis after CAS

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