Quantitative MRI for the assessment of subclinical CAD in T2DM

 描述（由申请人提供）：冠状动脉疾病（CAD）导致2型糖尿病（T2 DM）患者近60%的死亡。亚临床CAD可能会在很长一段时间内“悄悄”进展，直到冠状动脉事件（一组归因于心肌缺血的症状）袭击T2 DM患者。由于受到侵入性、X线暴露和肾毒性造影剂的限制，目前的诊断方法不足以估计亚临床病变的严重程度。 无记录或疑似心血管疾病的T2 DM患者的CAD。 在过去的十年中，磁共振成像（MRI）已成为一种有前途的非侵入性方法，用于量化重塑冠状动脉壁的形态和功能变化，传达冠状动脉事件的风险。最近的研究还提供证据表明，MRI可以评价心肌组织结构（纤维化和水肿）和心室运动/功能的变化。基于技术进步，我们假设亚临床CAD和相关心肌异常的MRI衍生特征有可能作为定量成像生物标志物，在T2 DM的病理生理学情况下呈现心血管风险。在本提案中，我们将建立一种新的60分钟MRI方案，以描述伴和不伴糖尿病肾病（DN）的T2 DM患者亚临床CAD的患病率和程度以及伴随的心脏结构-功能变化。糖尿病肾病是近40%的2型糖尿病患者常见的终末器官损害，被认为是冠心病事件的独立预测因子。然后，我们将冠状动脉/心脏测量与血液和尿液中的T2 DM/DN生物标志物联系起来。将进行这些研究，以初步测试这些MRI衍生特征的潜在临床价值，以表明T2 DM方案中心血管预防和靶器官保护的疗效。 指导的研究将有助于我的近期目标，即通过应用我在以前工作中获得的经验和知识来扩展我在筛选定量成像生物标志物方面的专业知识，以解决使用定量MRI的T2 DM患者未满足的临床需求。该项目也符合我的长期职业目标，即通过开展一项估计T2 DM人群心血管风险的临床研究，成为心血管医学的独立研究者。利用西北大学范伯格医学院（NU/FSM）独特的研究环境和世界一流的教育机会，我将接受临床心血管研究的强化培训和结构化教程，包括先进的心血管成像和糖尿病生物标志物识别/测试的实践培训;流行病学和生物统计学课程;研究研讨会和科学会议，以实现我的职业目标。

 DESCRIPTION (provided by applicant): Coronary artery disease (CAD) causes nearly 60% of deaths in patients with type 2 diabetes mellitus (T2DM). Subclinical CAD may "silently" progress over a long time period until coronary events, a group of symptoms attributed to myocardial ischemia, strike T2DM patients. Limited by invasiveness, X-ray exposure and nephrotoxic contrast media, current diagnostic methods are insufficient to estimate the severity of subclinical CAD in T2DM patients without documented or suspected cardiovascular diseases. Over the past decade, magnetic resonance imaging (MRI) has emerged as a promising noninvasive method for quantifying morphological and functional changes of remodeled coronary wall, which convey the risk of coronary events. Recent studies also provide evidence that MRI can evaluate changes in myocardial tissue structure (fibrosis and edema) and ventricular motion/function. Based on the technical advances, we hypothesize that MRI-derived characteristics of subclinical CAD and related myocardial abnormalities have the potential to serve as quantitative imaging biomarkers presenting the cardiovascular risk under pathophysiological circumstances of T2DM. In this proposal, we will build a novel 60-minute MRI protocol to delineate the prevalence and extent of subclinical CAD coupled with concomitant structure-function changes of the heart in T2DM patients with and without diabetic nephropathy (DN). DN is a common end-organ damage occurs in nearly 40% T2DM patients and has been considered as an independent predictor of coronary events. Then, we will link coronary/cardiac measurements to T2DM/DN biomarkers in the blood and urine. These investigations will be performed to preliminary test the potential clinical value of these MRI-derived signatures for indicating the efficacy of cardiovascular prevention and target-organ protection in T2DM regimens. The mentored research will facilitate my immediate goal of expanding my expertise in screening quantitative imaging biomarkers by applying the experience and knowledge acquired in my previous work to address unmet clinical needs for T2DM patients using quantitative MRI. The project also fits my long-term career goal of becoming an independent investigator in cardiovascular medicine by launching a clinical study for the estimation of cardiovascular risk in T2DM population. Taking advantage of the unique research environments and world-class educational opportunities at Northwestern University Feinberg School of Medicine (NU/FSM), I will receive intensive training and structured tutorials in clinical cardiovascular research, including hands-on training in advanced cardiovascular imaging and diabetic biomarker identification/testing; course work in epidemiology and biostatistics; and research seminars and scientific meetings, to achieve my career goals.