Magnetic Resonance Imaging of Vulnerable Plaque

描述(由申请人提供)：该项目的长期目标是确定易损斑块的特征，易损斑块被定义为动脉粥样硬化病变，导致血栓栓塞性并发症的风险增加。在这项提案中，我们计划使用高分辨率磁共振成像来研究可能导致易损斑块发展的机制。为了实现这些目标，我们将对一组中度颈动脉狭窄的受试者进行连续检查，以确定动脉从临床上沉默的稳定斑块演变为有症状的元凶病变时MRI表现的变化。组织学研究表明，易损斑块的特征是覆盖在血栓形成的坏死核心上的纤维帽变薄和断裂。其他研究也表明斑块新生血管的重要作用。斑块内的新生血管被认为是巨噬细胞渗透的一条途径，这些巨噬细胞表达基质金属蛋白酶，可以削弱纤维帽。此前的研究表明，MRI能够精确测量斑块体积，区分厚纤维帽和薄纤维帽或破裂的纤维帽，并识别有斑块新生血管的区域。本研究的具体目的是：1.检验纤维帽变薄和破裂先于斑块体积增加的假说2.检验这样的假设：新生血管增多的斑块更有可能从厚帽进展为薄或破裂的帽状病变，并且更有可能显示斑块体积的进展3.检验从厚帽向薄或破裂的帽状病变进展与缺血性神经事件的发生或帽状病变变薄或破裂的组织学证据相关的假说。更好地了解导致易损斑块形成的机制可能会为治疗提供新的靶点。此外，识别除管腔狭窄程度以外的其他高危斑块特征，可能会导致更好地选择患者进行干预，如颈动脉内膜切除术，并导致整体医疗费用的降低。

DESCRIPTION (provided by applicant): The long-term goal of this project is to identify characteristic features of the vulnerable plaque, defined as an atherosclerotic lesion that poses an increased risk for thromboembolic complications. In this proposal, we plan to study mechanisms that may lead to the development of the vulnerable plaque using high resolution MRI. To achieve these goals, we will serially examine a cohort of subjects with moderate carotid stenosis to identify changes in the MRI appearance of the artery as it evolves from a clinically silent, stable plaque to a symptomatic, culprit lesion. Histological studies suggest that the vulnerable plaque is characterized by thinning and rupture of the fibrous cap that overlies the thrombogenic necrotic core. Other studies also suggest an important role for plaque neovasculature. Neovessels within plaque are believed to represent a pathway for macrophage infiltration, and these macrophages have been shown to express matrix metalloproteinases that can weaken the fibrous cap. Previous studies have shown that MRI is capable of precisely measuring plaque volume, distinguish thick fibrous caps from thin or ruptured caps, and identify regions with plaque neovasculature. The specific aims of this study are: 1. Test the hypothesis that fibrous cap thinning and rupture precedes increase in plaque volume 2. Test the hypothesis that plaques with increased neovasculature are more likely progress from a thick cap to a thin or ruptured cap lesion, and are more likely to demonstrate progression in plaque volume 3. Test the hypothesis that progression from a thick cap to a thin or disrupted cap lesion correlates with the onset of an ischemic neurological event or histological evidence of cap thinning or rupture. A better understanding of the mechanisms leading to the development of the vulnerable plaque may provide new targets for therapy. Furthermore, identification of additional high-risk plaque features, other than the degree of lumen stenosis, may lead to better selection of patients for intervention, such as carotid endarterectomy, and result in overall reduction in health care costs.