Molecular Imaging of Collagen in Abdominal Aortic Aneurysms (AAA)

AAA是指主动脉扩张超过50%。AAA扩张可导致突然破裂，死亡率高达90%。当AAA直径超过55mm时，建议进行干预，但20%的AAA破裂<55mm。因此，提高对高危患者的识别和治疗是目前尚未满足的临床需求。描述AAA的生物组成和结构完整性是需要的，并且有可能改善仅依赖解剖信息的现有风险分层方法。胶原蛋白的转换在AAA的进展和稳定性中起着关键作用。目前，对胶原蛋白有选择性并区分I型和III型的分子成像探针有限或无法获得。这种探针将能够量化疾病进展过程中胶原蛋白水平的变化，并测试这些变化是否与动脉瘤大小、扩张或破裂相关。这将增强我们对疾病病理学的理解，并为开发非侵入性生物标志物铺平道路。新合成的胶原蛋白是否会导致生物化学和解剖学上的功能和稳定的网络，保留血管壁的机械特性需要更多的研究。我的目标是:1)描述胶原蛋白我三世改造和研究他们的角色在AAAs的发展和不稳定体内使用胶原蛋白核磁共振probe2)相关核磁共振成像发现与体外组织学变化来确定胶原蛋白营业额aneurysmsTechniques: -血管壁MRI ApoE老鼠注射了血管紧张素ⅱ(AngII)使用胶原蛋白标记探针钆-组织学、免疫组织化学和免疫印迹——semi-quantifying胶原蛋白我和III

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