Quantitative MRI for the assessment of subclinical CAD in T2DM

 描述(申请人提供)：在2型糖尿病(T2 DM)患者中，近60%的死亡是由冠状动脉疾病(CAD)引起的。亚临床冠心病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。受侵袭性、X射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的严重程度。 无心血管病史或可疑心血管疾病的2型糖尿病患者的冠心病在过去的十年里，磁共振成像(MRI)作为一种无创的方法，被用来量化冠状动脉重建后的形态和功能变化，这些变化传达了冠状动脉事件的风险。最近的研究也提供了证据，MRI可以评估心肌组织结构(纤维化和水肿)和心室运动/功能的变化。在技术进步的基础上，我们假设亚临床冠心病和相关心肌异常的MRI特征有可能作为反映T2 DM病理生理条件下心血管风险的定量成像生物标志物。在这项提案中，我们将建立一个新的60分钟的MRI方案来描绘T2 DM合并和不合并糖尿病肾病(DN)的患者中亚临床CAD的患病率和程度，以及伴随的心脏结构-功能变化。糖尿病肾病是一种常见的终末器官损害，发生在近40%的T2 DM患者中，已被认为是冠状动脉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生物标记物联系起来。这些研究将被用来初步检验这些MRI衍生的信号在提示T2 DM方案的心血管预防和靶器官保护的有效性方面的潜在临床价值。这项有指导的研究将促进我的近期目标，即通过应用我以前工作中获得的经验和知识，利用定量MRI解决T2 DM患者未得到满足的临床需求，从而扩大我在筛选定量成像生物标记物方面的专业知识。该项目也符合我的长期职业目标，即通过启动一项临床研究来评估T2 DM人群的心血管风险，从而成为心血管内科的独立研究员。利用西北大学范伯格医学院(NU/FSM)独特的研究环境和世界级的教育机会，我将接受临床心血管研究的强化培训和结构化教程，包括高级心血管成像和糖尿病生物标记物识别/测试的动手培训；流行病学和生物统计学的课程工作；以及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.