Study of the relation between blood flow and the age-dependent localisation of early atherosclerosis

Abstract

Atherosclerosis develops non-uniformly within the arterial system and the distribution of lesions has been observed to change with age. This thesis investigates the concept that the patchiness of the disease is related to local variations in blood flow. Based on the insights from a systematic literature review, a novel study was designed to analyse the relation between haemodynamic factors and age-dependent atherogenesis in the thoracic aorta of rabbits. Arterial geometries were reconstructed by micro-Computed Tomography of vascular corrosion casts, with particular attention to the anatomical accuracy of the dataset. Blood flow was simulated in these geometries using a spectral/hp element method. Distributions of traditional shear-related metrics were calculated and both qualitatively and quantitatively compared to maps of lesion prevalence. In addition, a time-averaged transverse wall shear stress was introduced. A geometric analysis of the dataset of rabbit thoracic aortas revealed a significant change with age in the degree of aortic taper. The geometric changes could explain age-related differences in flow characteristics, in particular in the extent of Dean-type vortical structures into the descending aorta and the strength of a dorsal streak of high shear. The comparative analysis of shear and lesion distributions did not unequivocally support the theory that lesions occur in regions of low shear. The novel haemodynamic metric, in combination with current metrics, enabled an improved identification of zones of multi-directional disturbed flow. In conclusion, this thesis adds to the understanding of the relation between blood flow and early atherosclerosis, and provides tools for use in future studies.