Objective: to explore the value of in vivo dynamic monitoring of abdominal aortic atherosclerosis (AS) by high field magnetic resonance (MR) imaging (MRI) in apoE-/- mice fed a high fat diet or infused with angiotensin.
Methods: high fat diet or angiotensin II infusion was applied to apoE-/- mice for establishment of abdominal aortic atherosclerosis model. Abdominal aorta MRI was performed at 3 time points (baseline, 3 and 6 months) in 13 high fat diet fed apoE-/- mice aged 10-12 months and 3 wild-type control mice; 10 apoE-/- mice aged 6 months were infused with angiotensin II (1000 or 500 ng × kg(-1)× min(-1), n = 5 each) or saline for 14 d through Osmotic minipump. The abdominal aortic artery MRI was performed at baseline and 14 d after infusion. Black blood sequences of FLASH T1 weighted images and Proton density weighted-T2 weighted dual echo images were obtained. At each observation time post MRI, mice (n = 3, 5 and 5 for high fat diet group and n = 5 and 5 for angiotensin II infusion group) were sacrificed for pathological examination of the abdominal artery.
Results: (1) the abdominal aorta atherosclerosis was identified in both high fat diet and angiotensin II treated apoE-/- mice but in WT controls. Lesion progression was documented in high fat diet fed apoE-/- mice characterized by significantly increased vessel wall (a marker of atherosclerotic burden, F = 29.94, P < 0.05) and gradually increased plaque signal in PDW and T2W images. Results derived from MRI corresponded histopathology findings in high fat diet fed apoE-/- mice (correlative coefficient = 0.84, 0.95, 0.90, P < 0.05, respectively). Both MRI and histology showed increased lipid composition and decreased fibrotic composition in these mice. (2) The vessel wall area increased significantly [(1.21 ± 0.21) mm(2) vs. (2.65 ± 0.48) mm(2), P < 0.05] and the abdominal aortic dissection aneurysms was identified in apoE-/- mice infused with high angiotensin II. The vessel wall area also increased [(0.85 ± 0.11) mm(2) vs. (1.01 ± 0.17) mm(2), P < 0.05] in low angiotensin II infused apoE-/- mice and the coefficient between MR and histopathology is 0.934.
Conclusion: abdominal aortic unstable plaque model could be established by both high fat diet and angiotensin II infusion in apoE mice, angiotensin II infusion can transiently accelerate the progression of AS and can induce abdominal aortic dissection. Serial MR black blood sequences could demonstrate the development and progression of atherosclerosis in mouse abdominal aorta with excellent agreement to histopathology finding in terms of atherosclerotic burden and plaque composition. Thus, MRI appears to be a useful tool for in vivo AS plaque dynamic monitoring in mice.