Abstract 5763: Dynamic Contrast-Enhanced MRI Detects Early Plaque Progression in a Rabbit Model of Atherosclerosis
Recent studies have used dynamic contrast-enhanced (DCE) MRI to quantify the rate of uptake of gadolinium contrast agents in atherosclerotic plaque. The transfer constant Ktrans, that quantifies the blood supply and permeability of the plaque, shows strong association with plaque inflammation. The purpose of this study was to explore the link between Ktrans and plaque inflammation in a model of early atherosclerotic lesion development. Twelve NZW rabbits were placed on a 0.2% cholesterol diet and underwent balloon injury of the descending aorta. After 12 weeks, all rabbits underwent a DCE-MRI exam, after which 6 were euthanized and perfusion fixed to harvest the atherosclerotic aortas. The remaining 6 were imaged again at 24 weeks and their aortas were harvested. The DCE-MRI procedure utilized a unique, high-speed, small field-of-view imaging technique with quadruple inversion recovery blood suppression (turbo spin echo, TR=800 ms, TE=9ms, 3mm slice thickness, 0.5mm in-plane resolution). This allowed us to observe enhancement of the vessel wall without contamination from enhancement of the adjacent lumen. The DCE-MRI results were analyzed to determine the average, relative Ktrans in the vessel wall and compared to histological assessments of the aortas. Ktrans was significantly higher at 6 months compared to 3 months within the same animals (p<0.005) and compared to those euthanized at 3 months (p<0.001). No difference was observed between the two groups at 3 months (p=0.4). Histologically, aorta cross sections at 6 months had lesions that were no thicker than those at 3 months (0.49 vs. 0.45mm, p=0.6), but complex lesion features including necrotic cores, intraplaque hemorrhage, neovessels, and deep clusters of macrophages were significantly more common at 6 months (82% vs. 18%, p<0.001). The transformation of the lesions from simple to complex morphologies from 12 weeks to 24 coincided with a significant rise in Ktrans. We attribute this rise to the development of neovessels in response to pro-inflammatory stimuli. We conclude that Ktrans can be used to probe lesion characteristics and complexity in early atherosclerosis, with applications in early diagnosis and treatment monitoring.
This research has received full or partial funding support from the American Heart Association, AHA Pacific/Mountain Affiliate (Alaska, Arizona, Colorado, Hawaii, Idaho, Montana, Oregon, Washington & Wyoming).