Molecular Imaging of Collagen in Abdominal Aortic Aneurysms (AAA)

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An AAA is the dilation of the aorta by more than 50%. Expansion of the AAA may lead to sudden rupture that has a high mortality rate of 90%. Intervention is recommended when AAA diameters exceed 55mm, however, 20% of ruptured AAA are <55mm. Thus, there is a current unmet clinical need to improve identification and treatment of high-risk patients. Characterising the biological composition and structural integrity of AAA is desired and has the potential to improve existing risk stratification approaches that solely depend on anatomical information.Collagen turnover is pivotal in the progression and stability of AAA. Molecular imaging probes that are selective to collagen and discriminate between types I and III are currently limited or not available. Such probes will enable quantification of changes in collagen levels during disease progression, and test whether these changes correlate with aneurysm size, expansion or rupture. This will enhance our understanding of disease pathology and pave the way for the development of a non-invasive biomarker. Whether the newly synthesised collagen leads to a biochemically and anatomically functional and stable network retaining the mechanical properties of the vessel wall requires more investigation. My aims: 1) To characterise collagen I and III remodelling and investigate their role on the development and instability of AAAs in vivo using a collagen MRI probe2) Correlate the MRI findings with ex vivo histology to determine the changes in collagen turnover on aneurysmsTechniques:- Vessel wall MRI in ApoE mice infused with Angiotensin-II (AngII) using Gadolinium labelled probes for collagen - Histology, immunohistochemistry and Western blotting - semi-quantifying collagen I and III