On the mechanical and morphological characterisation of calcification in diseased vascular tissue

Vascular calcification, a complex component that forms in the walls of arteries as part of advanced cardiovascular disease (CVD), triggers severe arterial complications and negatively impacts the success of endovascular intervention. An understanding of the influence of calcification on the structural integrity of the arterial tissue is a prerequisite in order to exploit its prognostic value as a mechanism to diagnose and treat patients with high risk CVD. However, the biomechanical link between calcification and arterial tissue remains unknown. To address this issue, this thesis aims to leverage improved understanding in the mechanics of calcified arterial tissue to support the stratification of arterial plaques suitable for specific endovascular treatments and to enhance abdominal aortic aneurysm (AAA) rupture prediction. Specialised experimental protocols were developed and employed to characterise circumferential stretch properties and rupture limits of whole carotid plaques simulating balloon angioplasty expansion. In addition, the fracture toughness properties of carotid plaques were measured using a custom-built guillotine tester determining forces required to fracture location-specific calcification during cutting balloon angioplasty (CBA). AAA wall properties were determined using standardised circumferential stretching tests, emulating the physiological stretch induced during the cardiac cycle, combined with a speckle-strain tracking algorithm quantifying localised strains. Experimental tests were coupled with characterisation techniques using Fourier transform infrared spectroscopy, high resolution micro-computed tomography, scanning electron microscopy and energy dispersive x-ray analyses. The structural complexity of calcification configurations in carotid plaques elicits an inhomogeneous circumferential stretch response whereby stretch is predominantly attained by the non-calcified tissue portion. Resistance to failure relies on interactions between specific calcified types and non-calcified tissue. Calcification volume fraction negatively correlates with stretch capability with respect to each calcification pattern. A calcification structure-volume parameter was therefore developed which represents a plaque’s stretch limits which marks a crucial starting point for the stratification of carotid plaques using calcification. Moreover, a strong relationship exists between calcification configurations, fracture mechanisms and associated toughness. Three plaque specific toughness profiles were defined identifying a classification of plaques that are related to localised regions of high toughness. This study underscores the importance of region specific characterisation for the improved design of CBA and to ensure successful calcified plaque fracture using appropriate forces. Moreover, AAA wall mechanical properties are controlled structurally by the load bearing capacity of the non-calcified fibrous tissue portion of the thinning wall with respect to the presence of calcification that are contiguous with the inner wall creating significant overstraining in surrounding tissue regions. Consequently, AAA diameter does not correlate with rupture as wall stresses are dependent on calcification presence rather than aneurysm diameter. An optimised preoperative CT imaging protocol, for characterising AAA walls, was subsequently devised using attuned resolution. Additionally, the relationship between novel matrix-gla-protein blood-based biomarkers and a plaques phenotype in ‘at risk’ cardiovascular patients was assessed to distinguish territory specific plaque development, using enzyme linked immunosorbent assay testing. This study demonstrates the potential future use of blood-based biomarkers to facilitate the early detection of patients at high risk and identify mechanisms involved in territory specific arterial plaque development.