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ItemNon-Newtonian Blood Flow Simulation to Improve Detection of Coronary Atherosclerosis and its ComplicationsThondapu, Vikas Satyaram ( 2018)Disturbances in arterial blood flow and endothelial shear stress (ESS) are associated with pathological processes underlying atherosclerosis and complications after stent placement. Image-based computational fluid dynamic (CFD) simulations allow in vivo estimation of ESS and other indices of flow disturbances. While low ESS is a relatively sensitive marker of future plaque progression, it remains too non-specific for clinical application. Possible improvements include incorporation of more realistic simulation methodologies. Although there are many possible ways to improve or change simulation accuracy, such as the choice of imaging, reconstruction techniques, boundary conditions, incorporation of arterial wall compliance, the primary aim of this thesis was to evaluate the effect of non-Newtonian rheology on ESS calculation. Although blood is a non-Newtonian fluid, most CFD studies assume blood to be a Newtonian fluid with constant viscosity. As opposed to the Newtonian model, non-Newtonian rheological models treat blood viscosity as a variable solved during CFD simulation. As a result, the non-Newtonian assumption offers two hypothetical advantages over the Newtonian model: 1) improved accuracy in calculation of traditional haemodynamic indices; 2) novel viscosity-based indices of blood flow disturbances are made available, and which may correlate with atherosclerosis. These primary hypotheses are investigated in this thesis by using CFD in combination with high-resolution optical coherence tomographic (OCT) imaging of atherosclerotic plaques and stents in patients with coronary artery disease. This work began with a randomised controlled trial of 60 patients comparing two second-generation drug-eluting stents using OCT imaging immediately after implantation and at 6 months (Chapter 8). Although there were no significant differences in the primary endpoint of stent malapposition, the platinum-chromium stent demonstrated a significantly higher incidence of late longitudinal deformation without concurrent events during 12-month clinical follow up. Next, non-Newtonian CFD simulation was performed in 7 patients who received a fully bioabsorbable coronary scaffold and OCT imaging immediately after implantation and 5 years later (Chapter 9). Low ESS between scaffold struts after implantation significantly improved by 5 years, and the overall ESS distribution narrowed to more normal physiologic levels associated with vascular quiescence. Up to 10-fold increases in blood viscosity were identified near scaffold struts, but peak viscosity in the scaffolded segment significantly decreased by 5 years. Comparison of CFD results using Newtonian versus non-Newtonian rheological models was then undertaken in 16 patients who had non-culprit plaques completely imaged in baseline and 6-month OCT imaging. By purely quantitative comparison of rheological models, the Newtonian model significantly underestimates ESS, resulting in up to a 40% higher estimate of vessel areas exposed to atherogenic low ESS (Chapter 10). While the Newtonian and non-Newtonian models can lead to different conclusions about the relationship of ESS with underlying plaque composition, non-Newtonian indices local blood viscosity (LBV) and local Reynolds number (ReL) are significantly and independently associated with underlying calcium and lipid, respectively (Chapter 11). Further, vessel areas exposed to high ESS along with both high and low ReL demonstrate increases in lipid over 6 months, indicating the role of high inertial and viscous forces in lipid accumulation (Chapter 12). Finally, blood flow disturbances were evaluated in 18 patients with acute plaque erosion and thrombus (Chapter 13). High gradient of ESS and high ReL were significantly associated with the presence of thrombus, implying their role in acute coronary syndrome due to plaque erosion.