On the quantification of arterial wall mechanical properties using invasive and non-invasive experimental investigations and analytical techniques

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University LondonCardiovascular diseases are the leading cause of death worldwide. Therefore, understanding their aetiology and development is a fundamental goal for biomedical research. Large arteries play a pivotal role in cardiovascular physiology; their elastic properties allow transforming the intermittent heart pulsation into a relatively steady flow. However, age-related microstructural changes of the arterial wall impair their compliant function, with negative consequences on the heart and other organs, including the brain. For this reason, arterial stiffness, assessed clinically by pulse wave velocity (PWV), has gained a central role in the prediction of cardiovascular risk. This thesis aimed to advance our understanding of the performance of the arterial wall, devising effective methods for the characterisation of its complex mechanical behaviour and, more specifically, stiffness both in vivo and ex vivo. The first part of this work comprises invasive ex vivo studies on arterial mechanics. The formulation of a novel tri-layered model of the arterial wall allowed investigating the layer-specific contribution to the macroscopic behaviour of arteries, providing a structural explanation to the pressure-dependence of arterial stiffness. Furthermore, the effects of the age-related remodelling of the wall microstructure on its non-linear behaviour were directly assessed via analysis of mechanical data of human donors’ aortae. The second part of this work consisted of the development and application of non-invasive techniques for the clinical assessment of arterial mechanics. First, the hysteresis area and the different slopes of the systolic and diastolic arms of the carotid pressure-diameter loops were used to quantify arterial viscoelasticity in a cohort of healthy people and hypertensive and diabetic patients. Second, exponential modelling of the carotid pressure-area relationship was used to define the relationship between local PWV, exponential parameters and blood pressure. This allowed assessing arterial stiffness independently of acute inter-subject differences in blood pressure. Furthermore, the viability of a new technique using ultrasound-based PWV to operate an exponential conversion of local diameter distension waveform into non-invasive pressure has been evaluated.Addenbrooke’s hospita