QUANT. MEASUREMENT OF ATHEROSCLEROTIC PLAQUES IN MRI

在美国，动脉粥样硬化引起的心血管疾病仍然是导致死亡的主要原因。动脉粥样硬化疾病的临床症状和发病是由于斑块不稳定，表现为溃疡、血栓形成和/或斑块内出血。许多研究都是为了了解动脉粥样硬化的发生、疾病的进展以及导致心脏病发作或中风的最终事件。然而，对于如何在体内无创地识别“易损”病变和纵向监测病变进展，人们所知相对较少。本文提出了一种利用病变指数定量测量动脉粥样硬化斑块特征，并将病变指数与临床症状的发展联系起来的方案。我们将重点研究颈动脉分叉处的晚期病变，因为1)它们与中风密切相关，2)它们可通过高分辨率MRI技术获得，3)颈动脉内膜切除术可获得颈动脉样本，这为我们提供了通过组织学检查样本来验证MRI结果的绝佳机会。该项目的长期目标是确定颈动脉中不稳定易损性动脉粥样硬化斑块的特征磁共振成像标记。目前还没有可靠的方法来描述这些病变与体内易损斑块相关的特征。具体目的是：1)建立/优化病变指数；2)检测脂质核的大小、纤维帽的厚度、新生血管的延伸（MR病变指数表达）是否与临床症状相关。这个项目建立在已经完成的和正在我们实验室进行的研究的基础上。识别高风险斑块的方法的改进将导致更好地选择患者进行干预。开发一种准确的、可重复的、定量的技术来直接评估动脉粥样硬化病变的状态和进展，将显著降低临床试验的成本。此外，病变指数将为跟踪病变的进展提供连续参数，而不是由病变类型评估提供的分类分析。最后，前瞻性的、连续的高分辨率颈动脉斑块MRI将提供一个独特的机会来检查从稳定病变到易损斑块的进展过程。

Cardiovascular disease due to atherosclerosis remains the leading cause of death in the United States. Clinical symptoms and morbidity that result from atherosclerosis disease are due to plaque instability and are manifested as ulceration, thrombosis, and/or intraplaque hemorrhage. Much research has been directed at understanding atherogenesis, the progression of the disease and the final events that lead to heart attack or stroke. However, relatively little is known about how to identify "vulnerable" lesions in vivo noninvasively and to monitor the lesion progression longitudinally. This proposal presents a plan to measure the atherosclerotic plaque features quantitatively using lesion indices and to correlate the lesion indices to the development of clinical symptoms. We will focus our study on advanced lesions at the carotid bifurcation, due to 1) their close association to stroke, 2) their accessibility by high resolution MRI techniques, and 3) the accessibility of carotid samples due to carotid endarterectomy that provide us with an excellent opportunity to verify the MRI results by examining the samples histologically. The long term goal of this project is to identify characteristic magnetic resonance imaging markers for unstable vulnerable atherosclerotic plaque in the carotid artery. At present there are no reliable means to characterize these lesions in terms of features that are associated with vulnerable plaque in vivo. The specific aims are: 1) to develop/optimize lesion indices and 2) to test whether the size of lipid core, the thickness of the fibrous cap, and the extend of neovascularization (as expressed by MR lesion indices) can be associated with clinical symptoms. This project builds on studies that have been performed and that are on going in our laboratory. Improved methods of identifying high-risk plaques will result in better selection of patients for intervention. Development of an accurate, reproducible, and quantitative technique for directly assessing the status and progression of atherosclerotic lesions will significantly reduce the cost of clinical trials. Furthermore, the lesion indices will provide continuous parameter for tracking progression of the lesion rather than a categorical analysis provided by a lesion type evaluation. Lastly, prospective, serial high-resolution MRI of the developing carotid plaque will provide a unique opportunity to examine the processes involved in progression form a stable lesion to vulnerable plaque.