Early in vivo discrimination of vulnerable atherosclerotic plaques that disrupt: A serial MRI study

Abstract Background and aims MRI has been validated as a suitable imaging modality for in vivo , non-invasive detection of atherosclerosis and has provided quantitative predictors of high-risk plaque. Here, we apply serial MRI to monitor the natural progression of plaques over a 3-month period in a rabbit model of atherothrombosis to determine differences over time between plaques that ultimately disrupt to form a luminal mural thrombus and plaques that remain stable. Methods Atherosclerotic plaques were induced in 12 male New Zealand White (NZW) rabbits by aortic endothelial injury and a 1% cholesterol diet. The rabbits were imaged 5 times: at baseline, 1, 2, and 3 months, and 48hr after pharmacological triggering for plaque disruption. Results Starting at 2 months, plaques that disrupted after triggering exhibited a higher remodeling ratio (RR, 1.05 ± 0.11 vs 0.97 ± 0.10, p = 0.0002) and a larger vessel wall area (VWA, 6.99 ± 1.54 mm 2 vs 6.30 ± 1.37 mm 2 , p = 0.0072) than the stable non-disrupted plaques. The same trends were observed at 3 months: plaques that disrupted had a higher RR (1.04 ± 0.02 vs 0.99 ± 0.01, p = 0.0209), VWA (8.19 ± 2.69 mm 2 vs 6.81 ± 1.60 mm 2 , p = 0.0001), and increased gadolinium uptake (75.51 ± 13.77% for disrupted vs 31.02 ± 6.45% for non-disrupted, p = 0.0022). Conclusions MR images of plaques that disrupted revealed larger VWAs, RRs, and increased gadolinium uptake at 2 months and continued progression of these vulnerable features between 2 and 3 months. Non-disrupted plaques had an independent history without these hallmarks of vulnerability. Our results show that MRI can provide early detection of plaques at a higher-risk for luminal thrombosis.