Thoracic aortic aneurysms (TAA) are life-threatening conditions with a rising prevalence in the UK, especially with an ageing population. Progressive vessel dilatation weakens the aortic wall over time leading to a sudden and often fatal acute event: type A acute aortic dissection (TAAD).
The diagnostic method for risk stratifying TAA in the clinical setting remains limited to a single diameter measurement from cross sectional imaging. The most up-to-date European and American guidelines cite only aneurysm size as a guide to evaluating the risk of rupture. The diameter threshold recommended (>55mm as measured in cross sectional imaging) is inadequate in many cases (almost half of aortic dissections occur below this cut-off). Meanwhile, the infrastructure and algorithms for the diagnosis and management of AAD remain considerably limited, leading to a persistently high rate of misdiagnosis.
In this thesis, I adopted a multimodal approach to characterising TAA in a cohort of patients focusing on four key areas of research: i) computational pathology; ii) targeted genetic sequencing; iii) mechanical characterisation of TAA tissue; and iv) aortic flow dynamics. Through this work, we have demonstrated three key findings. Firstly, medial degeneration occurs in hotspots of disease, affecting the outer curve more so, and microstructural features are directly related to in-vivo measures of mean arterial pressure and pulse wave velocity, as well as a potential link to underlying genomic variances. Secondly, the TAA wall is stiffer in the circumferential direction with a lower peeling force compared to longitudinally orientated aortic wall. Thirdly, wall shear stress (WSS) as deciphered from dynamic imaging, was higher on the outer curve of the aorta, and strongly associated with areas of reduced aortic tissue peeling force and aortic wall degeneration. Most importantly, TAA material properties were unrelated to aneurysm diameter.
These findings support the hypothesis of flow mediated degeneration in TAA pathology and set the stage for more translational work to further link aortic flow measurements with disease severity.