Imaging the Vascular Consequences of Lipid Deposition

代谢综合征患者，他们总是肥胖，表现出一系列的危险因素 心血管疾病，包括糖尿病、高血压和胆固醇异常 新陈代谢。这类患者的主要发病率是心肌梗塞和由加速反应引起的中风。 动脉硬化。促进动脉粥样硬化形成的复杂病理生理障碍还包括 慢性炎症、脂肪细胞内分泌功能障碍和血管顺应性异常。这个 胰岛素抵抗的发展是代谢综合征的一个关键的潜在特征，它导致 胰岛素和其他激素水平异常。我们假设除了强化的沉积之外 大的、特征良好的皮下和内脏脂肪储存中的脂肪，这是 代谢综合征是指脂肪在较小的储存库中不适当的沉积。这些不合适的商店包括 肝细胞甘油三酯、血管周围和心包甘油三酯，以及动脉粥样硬化胆固醇，它们 可作为疾病的局部标志。我们进一步假设，对这些脂质的欺骗是非侵入性的 以特定地点的方式，将提供对它们通过哪些机制施加系统性 影响并阐明确定不良后果的具体风险因素。磁共振成像 磁共振成像(MRI)是一种非侵入性工具，可以检测病理性脂肪沉积并识别早期动脉粥样硬化 血管发生了变化。我们将使用基于磁共振的技术来识别肥胖症患者的特定部位异常 患有代谢综合征但没有已知的动脉粥样硬化，正在接受医学监测的体重 失血和/或胃旁路(减肥)手术。我们将应用MRI来识别血管僵硬的变化和 这些变化与血管(动脉粥样硬化斑块)及其周围的脂质浓度有关 血管(甘油三酯)。我们将量化甘油三酯在肝脏和心脏周围的储存 血管(血管周围/心包脂肪)，并将这些发现与激素水平和 存在早期动脉粥样硬化性疾病。我们将监测这些参数在患者中的回归 成功减肥后的代谢同步。患有代谢综合征但处于晚期的患者 动脉粥样硬化患者正在接受颈动脉内膜切除术，我们将使用分子磁共振技术 确定炎症和斑块易损性的证据并进行体内和体外研究 量化脂肪。这项工作将阐明危险因素和临床表型之间的复杂相互作用， 通过演示哪些脂肪沉积对未来的健康最有害。一个重要的 结果我们的工作将是一种基于非侵入性磁共振的方案，将进一步对这一疾病的心血管风险进行分层 这是一种日益流行的患者队列，并提供了一种评估特定治疗效果的手段。

Patients with metabolic syndrome, who are invariably obese, exhibit a cluster of risk factors for cardiovascular disease including diabetes mellitus, hypertension, and abnormalities in cholesterol metabolism. The major morbidity in such patients is myocardial infarction and stroke caused by accelerated atherosclerosis. The complex pathophysiological disturbances that promote atherogenesis also include chronic inflammation, adipocyte endocrine dysfunction, and abnormalities in vascular compliance. The development of insulin resistance is a critical underlying feature of metabolic syndrome, which results in abnormal levels of insulin and other hormones. We hypothesize that in addition to the enhanced deposition of lipid in large, well-characterized subcutaneous and visceral fat stores, another unifying feature of metabolic syndrome is innapropriate deposition of lipid in smaller depots. These inappropriate stores include hepatocellular triglyceride, perivascular and pericardial triglyceride, and atherosclerotic cholesterol, which may serve as localized markers of disease. We further hypothesize that decection of these lipid stores noninvasively in a site-specific manner will provide new insights into mechanisms by which they exert systemic effects and illuminate specific risk factors for determining adverse outcomes. Magnetic resonance imaging (MRI) is a non-invasive tool that can detect the pathological lipid deposition and identify early atherosclerotic vascular changes. We will use MR-based techniques to identify site-specific abnormalities in obese patients with metabolic syndrome but without known atherosclerosis who are undergoing medically supervised weight loss and/or gastric bypass (bariatric) surgery. We will apply MRI to identify changes in vascular stiffness and correlate these changes to the concentration of lipid in the vessel (atherosclerotic plaque) and surrounding the blood vessel (triglyceride). We will quantify triglyceride stores in the liver and surrounding the heart and blood vessels (perivascular/pericardial fat), and associate these findings with hormone levels and the presence of early atherosclerotic disease. We will monitor regression of these parameters in patients with metabolic sydnrome following successful weight loss. In patients with metabolic syndrome but advanced atherosclerosis who are undergoing carotid endarterectomy, we will use molecular MR techniques to determine evidence of inflammation and plaque vulnerability and perform in vivo and ex vivo studies to quantify lipid. This work will elucidate the complex interplay between risk factors and clinical phenotype, through the demonstration of which lipid deposits are most detrimental to future health. An important outcome our work will be a non-invasive MR-based protocol that will further stratify cardiovascular risk in this increasingly prevalent cohort of patients, and provide a means to evaluate the efficacy of specific therapies.