Analysis of the Haemodynamic Factors Involved in Neointimal Hyperplasia Growth in Femoro-Popliteal Bypass Grafts Using Different Multi-scale, Patient-specific Modelling Approaches

Abstract

Introduction: Neointimal hyperplasia (NIH) is a major obstacle to the long term patency of peripheral vascular grafts. The disease has a complex aetiology which is influenced, among other phenomena, by mechanical forces such as shear stresses acting on the arterial wall. Objectives: The aim of this work is to assess the impact of haemodynamic factors in a patient-specific, multi-scale modelling framework developed using computational fluid dynamics (CFD) and mathematical biology, for the quantification of NIH growth. Methods: Simulations were performed on datasets from two femoro-popliteal and one femoro-distal bypass patients. Patient data (imaging and haemodynamics) was obtained from Yale University School of Medicine. In this work, smooth muscle cells and collagen in the vascular tissue were modelled using ordinary differential equations. These were linked to wall shear stress (computed using CFD) through its relationship with nitric oxide and growth factors. Results: Results obtained by simulating the growth via the combined CFD and mathematical biology framework seems to outperform analyses performed with haemodynamic indices (obtained by CFD) alone, enabling to pinpoint the locations of NIH and to achieve quantification of its growth. For instance, when only accounting for the time-averaged wall shear stress in the rigid wall model, luminal narrowing was underestimated by up to 19.3%, while when also accounting for oscillatory behaviour the model was able to reach the amount of occlusion present (as measured in the CT scans), with an average overestimate of 10%. Conclusion: The study presents a patient-specific, multiscale simulation framework to model NIH progression. While a previous version of the model underestimated the occlusion of the lumen due to NIH, the results presented show an improvement in estimating occlusion by accounting for movement of the arterial wall, oscillatory behaviour of shear stress and non-Newtonian properties of blood viscosity.

An in silico study of the influence of vessel wall deformation on neointimal hyperplasia progression in peripheral bypass grafts

“…Previous findings [31] highlighted the importance of considering the non-Newtonian behaviour of viscosity, but showed no difference in terms of NIH growth estimate at the proximal and distal anastomosis for a parabolic or plug flow inflow condition, hence, a plug flow condition was used at the inlet, and a non-Newtonian Carreau-Yasuda model of viscosity [32] was used. Patient-specific doppler ultrasound-derived flowrate waves (QIN,1, QIN,2, QIN,3) were applied at the inlets as shown in Figure 2.…”