Abstract

Non-invasive monitoring of human atherosclerotic plaque progression would be extremely valuable for determining the characteristics of vulnerable plaques before they rupture and for evaluating therapeutic interventions. We have shown that MRI is a reliable method for differentiating stable and vulnerable aortic atherosclerotic plaques in a rabbit model of atherothrombosis. In this study, we imaged rabbits at 4 time points (baseline, 1, 2 and 3 months) to monitor the progression of plaques and investigate when stable and vulnerable plaques can be differentiated. MR images and histology of two plaques in the same rabbit aorta are compared below. The top row of black blood (BB) T1 images (with fat suppression) show no significant changes in the lumen or the vessel wall area, and no thrombus in the stable plaque after triggering to induce plaque rupture. The histology showed an intact fibrous cap, overlying diffuse lipids. In comparison, there is a marked increase in vessel wall area in the vulnerable plaque (from 4.1 to 15 mm2 over 3 months). The second row (T1BB FS with Gd) shows some uptake of Gd into the stable plaque and surrounding tissue, but the vulnerable plaque showed rapidly increased Gd uptake between months 2 and 3. The vulnerable plaque also showed a large luminal thrombus in the MR images of the live rabbit and in the corresponding histology slice. In addition, the vulnerable plaque showed excessive outward remodeling at 2 months (data not shown). Our study shows a progression of vulnerable features, clearly evident at 2 months, in the plaque that disrupted. We are currently investigating whether therapies initiated at 2 months will reduce the progression of plaque vulnerability.

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