Accurate Perfusion MRI for Improved Diagnosis of Microvascular Coronary Disease

描述(申请人提供)：胸痛或心绞痛影响大约800万美国成年人，每年导致超过150万人住院治疗，相关费用为1900亿美元。然而，接受冠状动脉造影术的心绞痛稳定患者中，近一半被发现没有阻塞性冠状动脉疾病。微血管冠状动脉功能障碍(MCD)被认为是无梗阻性冠状动脉疾病时心绞痛症状的主要潜在病因。通过纳入跨学科培训内容和指导研究，该项目旨在提高基于心脏磁共振(CMR)首过心肌灌注成像的MCD的非侵入性诊断。CMR灌注成像为这一以女性为主的人群提供了一种无辐射的方法，并实现了高空间分辨率，从而可以描绘心内膜下层。然而，尽管取得了重大进展，但仍然存在一些根本性的挑战，限制了当前CMR方法可靠地检测MCD的能力，最重要的是存在所谓的暗边缘伪影，它显著降低了心内膜下心肌灌注储备(MPR)测量的准确性和可靠性。在这个项目中，我们建议开发一种创新的灌注CMR方法来克服这些限制。我们的中心假设是，在识别MCD患者方面，开发的技术将显著优于传统的CMR。我们将在我们最近的突破性工作的基础上，改善灌注CMR的质量，特别是最大限度地减少暗边缘伪影和非心电门控成像，并将开发一种创新的灌注CMR方法，使心内膜下MPR能够准确定量。从定性到定量的心脏成像研究的这一转变充分利用了参与这项建议的多学科指导团队的独特优势，他们在开发创新的CMR方法和应用于CAD和MCD的临床成像研究方面有着良好的记录，包括NHLBI赞助的WISE研究。K99阶段的指导计划包括一个跨学科计划，旨在为候选人提供开发和应用定量心脏成像方法的深入而不可避免的广泛培训，并获得过渡到心脏成像领域独立学术生涯所需的技能。R00独立阶段的研究战略旨在系统地开发一种创新的伪影最小化的CMR灌注成像方法，并进行试点患者研究，以获得有关所开发的CMR方法有效性的初步数据，从而为后续的独立拨款申请奠定基础。该项目的成功完成将克服定量灌注CMR成像方面的主要技术挑战，并使其能够可靠地检测受损的心内膜下MPR，这可能为疑似MCD患者的诊断和长期监测提供可靠的工具，并可能成为涉及此类患者的临床试验的终点。

DESCRIPTION (provided by applicant): Chest pain or cardiac angina affects about 8 million U.S. adults and leads to more than 1.5 million hospitalizations per year with $190 billion in associated costs. However, nearly half of stable patients with cardiac angina who undergo coronary angiography are found to have no obstructive coronary artery disease. Microvascular coronary dysfunction (MCD) is known to be a major underlying etiology for anginal symptoms in the absence of obstructive coronary disease. By incorporating cross-disciplinary training components and mentored research, the proposed project aims to improve the non-invasive diagnosis of MCD based on cardiac magnetic resonance (CMR) first-pass myocardial perfusion imaging. CMR perfusion imaging provides a radiation-free approach for this predominantly female population and achieves a high spatial resolution thereby allowing for delineation of the subendocardial layer. However, despite major advances, there are fundamental challenges that limit the capability of current CMR methods to reliably detect MCD, most importantly the presence of the so-called dark-rim artifacts, which significantly reduce the accuracy and reliability of subendocardial myocardial perfusion reserve (MPR) measurements. In this project, we propose to develop an innovative perfusion CMR method that overcomes such limitations. Our central hypothesis is that the developed technique will significantly outperform conventional CMR in identifying patients with MCD. We will build upon our recent breakthrough work on qualitative improvements for perfusion CMR, specifically minimizing dark-rim artifacts and non-ECG-gated imaging, and will develop an innovative perfusion CMR method that enables accurate quantification of subendocardial MPR. This transition from qualitative to quantitative cardiac imaging research for the candidate leverages unique strengths of the multi-disciplinary mentoring team involved in this proposal with a track record for developing innovative CMR methods and clinical imaging research applied to CAD and MCD, including the NHLBI-sponsored WISE study. The outlined mentoring plan for the K99 phase incorporates a cross-disciplinary program designed to provide the candidate with an in-depth yet inevitably broad training in developing and applying quantitative cardiac imaging methodology, and to obtain skills necessary for transitioning into an independent academic career in the field of cardiac imaging. The research strategy in the R00 independent phase is designed to systematically develop an innovative artifact-minimized CMR perfusion imaging methodology, and to conduct a pilot patient study to obtain initial data on the effectiveness of the developed CMR method, thereby laying the groundwork for a subsequent independent grant application. Successful completion of this project will overcome major technical challenges in quantitative perfusion CMR imaging and will empower it with the capability to reliably detect impaired subendocardial MPR, which may provide a reliable tool for diagnosis and long-term monitoring of patients with suspected MCD, and potentially an end-point for clinical trials involving such patients.