Computational blood flow studies on model and realistic geometries.

Study of blood flow inside arteries is physiologically significant and computationally challenging. Vascular diseases are the leading causes of death worldwide. Since the geometry is characterized by twisted, bended, bifurcated, trifurcated and multi-branched structure, the numerical modeling of blood flow is highly complicated. Blood flow is also complex due to the unsteady (pulsatile), three dimensional and helical nature. The computational work in this thesis contains flow simulation of few idealistic models followed by a thorough numerical study of a realistic thoracic abdominal aorta. The three dimensional, viscous Navier Stokes equations are solved explicitly using characteristic based split (CBS) method for time discretization and standard Galerkin method for spatial discretization by imposing physiologically relevant boundary conditions. The artificial compressibility method, which is found to be efficient for biomedical flow problems, has also been discussed briefly. The velocity vectors, wall shear stress contours and pressure distribution plots presented in this thesis provide important insight into actual behavior of blood flow inside arteries. The meshes contain boundary layers for accurate calculation of wall shear stress. The idealistic models studied under steady conditions are straight and s-shaped arteries. All these idealistic models represent healthy arteries. For idealistic models, it is found that complex secondary flow, pressure drop and the WSS vary with change in geometrical configurations and flow rate. In addition to idealistic models, a realistic thoracic aorta with an aneurysm has been studied, by prescribing fully developed pulsatile wave form at the inlet and ail four exits. The patient specific geometrical data of this thoracic aorta has been obtained with the aid of standard CT scans and processed by AMIRA to construct an initial mesh. In this realistic simulation, WSS is found to be low at the beginning of the cardiac cycle, increases to maximum at the peak flow rate and decreases rapidly as the velocity drops. This research work involving fluid dynamical studies in arteries concludes that hemodynamic quantities such as Oscillatory shear index (OSI), flow separation and reversal regions and blood pressure may play a vital role in pathogenesis of arterial anomalies. The Numerical models and the required CBS and velocity profile generation codes have been provided by the team

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

Multiscale Fluid-Structure Interaction Models Development and Applications to the 3D Elements of a Human Cardiovascular System

Cardiovascular diseases (CVD) are the number one cause of death of humans in the United States and worldwide. Accurate, non-invasive, and cheaper diagnosis methods have always been on demand as cardiovascular monitoring increase in prevalence. The primary causes of the various forms of these CVDs are atherosclerosis and aneurysms in the blood vessels. Current noninvasive methods (i.e., statistical/medical) permit fairly accurate detection of the disease once clinical symptoms are suggestive of the existence of hemodynamic disorders. Therefore, the recent surge of hemodynamics models facilitated the prediction of cardiovascular conditions. The hemodynamic modeling of a human circulatory system involves varying levels of complexity which must be accounted for and resolved. Pulse-wave propagation effects and high aspect-ratio segments of the vasculature are represented using a quasi-one-dimensional (1D), non-steady, averaged over the cross-section models. However, these reduced 1D models do not account for the blood flow patterns (recirculation zones), vessel wall shear stresses and quantification of repetitive mechanical stresses which helps to predict a vessel life. Even a whole three-dimensional (3D) modeling of the vasculature is computationally intensive and do not fit the timeline of practical use. Thus the intertwining of a quasi 1D global vasculature model with a specific/risk-prone 3D local vessel ones is imperative. This research forms part of a multiphysics project that aims to improve the detailed understanding of the hemodynamics by investigating a computational model of fluid-structure interaction (FSI) of in vivo blood flow. First idealized computational a 3D FSI artery model is configured and executed in ANSYS Workbench, forming an implicit coupling of the blood flow and vessel walls. Then the thesis focuses on an approach developed to employ commercial tools rather than in-house mathematical models in achieving multiscale simulations. A robust algorithm is constructed to combine stabilization techniques to simultaneously overcome the added-mass effect in 3D FSI simulation and mathematical difficulties such as the assignment of boundary conditions at the interface between the 3D-1D coupling. Applications can be of numerical examples evaluating the change of hemodynamic parameters and diagnosis of an abdominal aneurysm, deep vein thrombosis, and bifurcation areas

Experimental Validation of Enhanced Magnetic Resonance Imaging (EMRI) Using Particle Image Velocimetry (PIV)

Flow-sensitive four-dimensional Cardiovascular Magnetic Resonance Imaging (4D Flow CMR) has increasingly been utilised to characterise patients' blood flow, in association with patiens' state of health and disease, even though spatial and temporal resolutions still constitute a limit. Computational fluid dynamics (CFD) is a powerful tool that could expand these information and, if integrated with experimentally-obtained velocity fields, would enable to derive a large variety of the flow descriptors of interest. However, the accuracy of the flow parameters is highly influenced by the quality of the input data such as the anatomical model and boundary conditions typically derived from medical images including 4D Flow CMR. We previously proposed a novel approach in which 4D Flow CMR and CFD velocity fields are integrated to obtain an Enhanced 4D Flow CMR (EMRI), allowing to overcome the spatial-resolution limitation of 4D Flow CMR, and enable an accurate quantification of flow. In this paper, the proposed approach is validated in a U bend channel, an idealised model of the human aortic arch. The flow patterns were studied with 4D Flow CMR, CFD and EMRI, and compared with high resolution 2D PIV experiments obtained in pulsatile conditions. The main strengths and limitations of 4D Flow CMR and CFD were illustrated by exploiting the accuracy of PIV by comparing against PIV velocity fields. EMRI flow patterns showed a better qualitative and quantitative agreement with PIV results than the other techniques. EMRI enables to overcome the experimental limitations of MRI-based velocity measurements and the modelling simplifications of CFD, allowing an accurate prediction of complex flow patterns observed experimentally, while satisfying mass and momentum balance equations

The Oscillatory Shear Index: Quantifications for Valve Tissue Engineering and a Novel Interpretation for Calcification

Heart valve tissue engineering (HVTE) stands as a potential intervention that could reduce the prevalence of congenital heart valve disease in juvenile patients. Prior studies in our laboratory have utilized mechanobiological testing to quantify the forces involved in the development of heart valve tissue, utilizing a Flow-Stretch-Flexure (FSF) bioreactor to condition bone marrow stem cells (BMSCs)-derived valve tissue. Simulations have demonstrated that certain sets of flow conditions can introduce specific levels of oscillatory shear stress (OSS)-induced stimuli, augmenting the growth of engineered valves as well as influencing collagen formation, extracellular matrix (ECM) composition and gene expression. The computational findings discussed in this thesis outline the methods in which flow conditions, when physiologically relevant, induce specific oscillatory shear stresses which could not only lead to an optimized valve tissue phenotype (at 0.18≤ OSI≤ 0.23), but could identify native valve tissue remodeling indicative of aortic valve disease

Pressure and Flow Wave Propagation in Patient-Specific Models of the Arterial Tree

Blood flow in the arterial circulation induces hemodynamic forces that play an important role in various forms of vascular diseases. Temporal variation of the wall shear stress seems to play a significant role in atherogenesis and plaque stability. Flow induced wall shear stress has been linked to growth and possibly rupture of the aneurysm wall. Hemodynamic forces are patient-specific and difficult to assess in the clinic. At present, there is no in vivo measurement technique that enables measurement of hemodynamic forces to the degree of precision needed. However, when imaging modalities used frequently in clinical routine re-create high-definition, patient geometric quantification of the blood vessel, they can be employed as a base for creating predictive hemodynamic models. Which in the case of understanding healthy vs. pathologic blood flow within the cerebral or systemic circulation, renders this an interesting approach. First, we developed a "generic 1D" distributed model of the human arterial tree including the primary systemic arteries and coupled this to a heart model. The fluid mechanics equations were solved numerically to obtain pressure and flow throughout the arterial tree. A nonlinear viscoelastic constitutive law for the arterial wall was considered while distal vessels were terminated with a three-element Windkessel model. The coronary arteries were modeled assuming a systolic flow impediment proportional to ventricular varying elastance. The model predictions were validated with noninvasive measurements of pressure and flow performed in young volunteers. Flow in the large arteries was visualized with magnetic resonance imaging, cerebral flow detected with ultrasound Doppler and blood pressure measured with applanation tonometry. Model predictions at different arterial locations compared well to measured flow and pressure waves at the same anatomical points. Thus, the generic 1D model reflected the flow and pressure measurements of the "average subject" of our volunteer population. Following the same approach as the generic 1D model, we built and validated a patient-specific model. In this case, geometric data, flow and pressure measurements were obtained for one person. The model predicted pressure and flow waveforms in good agreement with the in-vivo measurements with regards to wave shape and features. Comparison with a generic 1-D model has shown that the patient-specific model better predicted pressure and flow at specific arterial sites. Overall, the patient-specific 1-D model was able to predict pressure and flow waveforms in the main systemic circulation, whereas this was not always the case for a generic 1-D model. The inherent underestimation of energy losses of the 1-D wave propagation model, due to bifurcations, non-planarity and complex geometry, were examined. The 1-D model was compared to a rigid wall 3-D computational fluid dynamic model. Newtonian and non-Newtonian blood properties were studied and the longitudinal pressure distribution along the arteries was compared with the 1-D patient-specific model mean pressure prediction. The results indicated that pressure drop is significant only in small diameter vessels such as the precerebral and cerebral arteries. In these vessels the 1-D model in comparison to 3-D models consistently underestimated pressure drop. The complex flow patterns resulting from asymmetry and bifurcation yield shear stresses in the 3-D model that were greater than the 1-D model. A 3-D unsteady fluid structure interaction simulation in a patient-specific model was performed to simultaneously capture the flow details, given by the 3-D model, and wave propagation phenomena, provided by the 1-D model. The 3-D unsteady fluid structure interaction approach is the most computationally intense and cumbersome, but it allows physiological simulations with a high level of detail and accuracy. For instance, this approach could be relevant to obtain blood flow details in regions that are prone to atherosclerotic plaques or development of aneurysms. The 3-D fluid structure interaction simulation was performed for a patient-specific aorta. Important clinical parameters such as wall shear stress were quantified and significant differences were found in comparison to the rigid wall 3-D simulation indicating the relevance of a fluid structure interaction approach. A comparison of the fluid structure interaction to an equivalent 1-D model resulted in good reproduction of the pressure and flow waveforms. The effect of a decreased compliance of the arterial tree on hemodynamical parameters has been assessed with the use of a 1-D model. Local, proximal aorta and global stiffening of the arterial tree were modeled and led to two different mechanisms that contribute to the increase in central pulse pressure. They probably both contribute to systolic hypertension and their relative contribution depends on the topology of arterial stiffening and geometrical alterations taking place in aging or in disease. All these patient-specific models are about to being in use in a clinical environment and will be useful for providing better diagnostics and treatment planning in a near future

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