MRI Evaluation Of Arterial Plaque Vulnerability Experimental Study Atherosclerosis

Part I:In Vivo Study of Atherosclerotic Plaque Burden by High-Resolution MRI in Rabbit ModelPurpose:To build a rabbit model of atherosclerosis at abdominal aorta appropriate for imaging study, investigate the feasibility of studying atherosclerotic plaque morphology and components using high-resolution MR imaging techniques on a clinical MR scanner, and finally evaluate the accuracy of MRI images in analyzing plaque burden.Background:Asian population tend to have more intracranial arterial atherosclerotic lesions than extracranial lesions. Intracranial lesions have also shown a closer correlation with stroke. To build a model appropriate for plaque vulnerability study at rabbit aorta, which has a similar caliber with human middle cerebral artery, is valuable for developing imaging approaches for plaques in small caliber arteries, and will promote the clinical use of high-resolution MRI of intracranial arteries.Methods:Twenty New Zealand White rabbits were assigned to model group (n=16) or control group (n=4). Aortic atherosclerosis was induced through endothelial denudation combined with a cholesterol-enriched diet. Serum lipid markers were measured in six rabbits before and after initiation of high-cholesterol diet.10-16weeks after endothelial denudation, all rabbits underwent MRI scan using a clinical1.5T MR system. Axial high-resolution images of abdominal aorta were acquired with T2-weighted fast spin-echo sequence. Perfusion-fixation combined with ex vivo fixation was performed within twelve hours after scan and specimens with the most prominent lesions were harvested. Morphology and components were compared between HE stained images and T2-weighted images. We further performed Pearson correlation analysis between HE images and T2-weighted images regarding area measurements of lumen and arterial wall. Masson staining and immunohistochemical stainings with CD31and macrophage antibodies were used to study pathologic characteristics. Results:Lipid accumulation and fibrous proliferation were observed in atherosclerotic rabbits. Model rabbits exhibited decreased lumen area and increased arterial wall area compared with control rabbits. Different degrees of inflammation, outward remodeling and neovascularization were seen in induced plaques. Plaques showed heterogeneous signal intensities (SI) in T2-weighted images. Fibrous tissue tended to have high SI while lipid accumulation tended to have low SI. However, both of them could exhibit various SI according to their different status. Lumen area and arterial wall area measured on T2-weighted images had significant correlations with those measured on histological images (lumen area:r=0.7503, arterial wall area:r=0.8666, both P<0.05)。Conclusion:Endothelial denudation with high-cholesterol diet can successfully induce atherosclerosis plaque formation at abdominal aorta, which provides a good setting for preclinical study of plaque vulnerabilities regarding fibrous cap, lipid core, inflammation activity, outward remodeling and neovascularization. In vivo high-resolution MRI can visualize plaque morphology and components in small caliber artery model. MRI measurements have a positive correlation with histological measurements and can be used to evaluate plaque burden. Part II:Analysis of Neovasculature in Atherosclerotic Plaques Using Dynamic Contrast-Enhanced MRI:A Preliminary Study in Rabbit ModelPurpose:The study was designed to determine whether neovessels in atherosclerotic plaques can be quantified by dynamic contrast-enhanced MRI in rabbit model, and to explore Gd-DTPA enhancement mechanism for atherosclerotic plaques.Background:Neovascularization is considered to be related to leukocyte infiltration and thus a hallmark of vulnerability. A noninvasive imaging technique that can identify and quantify neovasculature in plaques would be of great potential clinical utility. DCE-MRI is an imaging technique extensively being used to study the vascularity of tumors. It is a promising technique that may provide quantitative information of neovasculature in atherosclerotic plaques.Methods:Atherosclerotic plaques were induced in aortas of twelve New Zealand White rabbits by a combination of endothelial denudation and high-cholesterol diet.10-13weeks after surgery, DCE-MRI was performed in model rabbits and another four control rabbits. Four rabbits from model group underwent a second DCE-MRI at the identical slices with the first one four weeks later.35to50T1-weighted images were obtained at71-second intervals. Gd-DTPA was injected coincident with the third scan via marginal ear vein. Specimens were harvested within twelve hours after scan for HE staining and CD31immunohistochemical staining, which was used to highlight neovessels. Plaque enhancement patterns were studies and compared with histological findings. Signal intensity of each plaque section was normalized to pre-contrast signal intensity of psoas muscle, after which signal intensity versus time curve was drawn. Pearson correlation coefficient was used to reveal association between histological neovessel count and descriptive parameters derived from signal intensity versus time curve. Difference of parameters derived from two serial DCE-MRIs was analyzed by using paired t test. Results:Plaques were significantly enhanced by Gd-DTPA. Enhancement pattern could be described as "fast-in and slow-out". Differences in enhancement were observed between tissues, with fibrous tissue enhanced more than lipid aggregation and leukocyte foci. Peak enhancement, initial slope and area under the curve at early phase derived from signal intensity-time curve had significant correlations with neovessel count. Parameters from two DCE-MRIs with four weeks gap were not statistically significant different.Conclusion:Neovascularization may be one of the reasons for plaque enhancement by Gd-DTPA. DCE-MRI has the potential to indicate the extent of neovasculature within plaques.