Abstract 19913: In vivo Characterization of a New Abdominal Aortic Aneurysm (AAA) Mouse Model with Conventional and Molecular MRI
The turnover of collagen plays a critical role in the pathogenesis, progression and rupture of Abdominal Aortic Aneurysms (AAA). Non-invasive imaging of this process may represent an opportunity to identify unstable AAAs and initiate intervention. We used a model of AAA where a combination of angiotensin II infusion and TGF-β neutralization Resultsed in a high incidence of AAA rupture in C57BL/6 mice. We evaluated the AAA temporal progression using conventional high resolution MRI, while the turnover of collagen was evaluated with nanoparticle-enhanced MR molecular imaging. Multi-contrast MRI was performed at 9.4T. In vitro specificity of CNA35 micelles for collagen was first established. AAAs were induced and mice were injected with CNA35 micelles or the non-binding mutant CNA35 micelles (both groups n=5, 50 μmol Gd/kg). T1 weighted images were acquired before and 32 hours post injection. MR images were corroborated with matched histological sections stained for collagen, while further examination was performed using confocal microscopy. Multi-contrast MRI revealed an increase of the aortic diameter and showed the primary fibrotic response in the aortic wall as well as the rupture of the medial layer with blood infiltrating the adventitial tissue, in which resulted in the formation of a false channel. Injection of CNA35 micelles resulted in significant MR signal enhancement in the aneurismal wall over mutant CNA35 micelles (Figure). Fluorescence confocal microscopy revealed the colocalization of CNA35 micelles with collagen-I marked by immunofluorescence. Importantly, the MR enhancement pattern differed in the animals and was evaluated, via histological examinations, to represent collagen degradation and thus the degree of AAA progression. In Conclusions, multi-contrast MRI enabled us to longitudinally monitor AAA progression. MR molecular imaging offered an opportunity to image the turnover of collagen and identify different stages of AAA progression.
- © 2010 by American Heart Association, Inc.