Neovasculature, Plaque Rupture And Progression by MRI

项目2的总体目标是使用高分辨率磁共振成像(MRI)来研究 颈动脉粥样硬化从亚临床病变发展为高危斑块可能涉及的机制。具体地说，我们将研究病变颈动脉中新生血管、纤维帽状态和斑块负荷之间的关系。组织学研究表明，高危斑块的特征是覆盖血栓样坏死核心的纤维帽变薄和破裂，这反过来可能导致血管血栓闭塞或下游材料栓塞。此外，帽状破裂伴壁血栓形成可能导致整体斑块的增加。 音量。其他研究表明，斑块新生血管起着重要作用。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。 在NIH的资助下，我们已经证明MRI能够精确测量斑块体积，区分厚纤维帽和薄纤维帽和破裂的帽，并识别有斑块新生血管的区域。我们计划对275名早期、亚临床颈动脉粥样硬化患者进行磁共振增强前后的系列检查。这项研究的具体目的是检验三个关于进展为高动脉粥样硬化的机制的假设：1.纤维帽变薄和破裂先于斑块负荷的增加；2.MRI确定的病变颈动脉中新生血管的增加预示着斑块负荷的进展的更高风险；以及3.新生血管增加的斑块更有可能从厚帽进展为薄的或破裂的帽状病变。对机制有更好的理解 导致高危斑块的发展可能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。

The overall goal of Project 2 is to use high-resolution magnetic resonance imaging (MRI) to study mechanisms that may be involved in the progression of carotid atherosclerosis from a sub-clinical lesion to a high-risk plaque. Specifically, we will examine the relationships between neovasculature in the diseased carotid artery, fibrous cap status, and plaque burden. Histological studies suggest that the high-risk plaque is characterized by thinning and rupture of the fibrous cap that ovedies the thrombogenic necrotic core, which in turn may lead to thrombotic occlusion of the vessel or embolization of material downstream. Furthermore, cap rupture with overlying mural thrombus formation may lead to an increase in overall plaque volume. Other studies 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. With funding from the NIH, we have shown that MRI is capable of precisely measuring plaque volume, distinguish thick fibrous caps from thin and ruptured caps, and identify regions with plaque neovasculature. We plan to serially examine 275 subjects with early, subclinical carotid atherosclerosis with pre-and postcontrast enhanced MRI. The specific aims of this study are to test three hypotheses regarding mechanisms of progression to a high-dsk]esion: 1. that fibrous cap thinning and rupture precedes increase in plaque burden; 2. that increased neovasculature in the diseased carotid artery, as identified by MRI, predicts a higher risk for progression in plaque burden; and 3. that plaques with increased neovasculature are more likely progress from a thick cap to a thin or ruptured cap lesion. A better understanding of the mechanisms leading to the development of the high-risk 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.