Accurate Perfusion MRI for Improved Diagnosis of Microvascular Coronary Disease

胸痛或心绞痛影响约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，在接受冠状动脉造影的稳定型心绞痛患者中，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）是已知的心绞痛症状的主要潜在病因，在没有阻塞性冠状动脉疾病。通过结合跨学科的培训内容和指导研究，拟议的项目旨在改善基于心脏磁共振（CMR）首过心肌灌注成像的MCD非侵入性诊断。CMR灌注成像为这一主要为女性的人群提供了一种无辐射的方法，并实现了高空间分辨率，从而允许描绘内膜下层。然而，尽管取得了重大进展，但仍存在根本性挑战，限制了当前CMR方法可靠检测MCD的能力，最重要的是所谓暗边伪影的存在，这显着降低了心内膜下心肌灌注储备（MPR）的准确性和可靠性测量。在这个项目中，我们建议开发一种创新的灌注CMR方法，克服这些限制。我们的中心假设是，开发的技术将显着优于传统的CMR在识别MCD患者。我们将建立在我们最近的突破性工作的定性改进灌注CMR，特别是最大限度地减少暗边伪影和非心电图门控成像，并将开发一种创新的灌注CMR方法，使准确定量的subendoembryonic MPR。这种从定性到定量心脏成像研究的转变利用了参与该提案的多学科指导团队的独特优势，该团队在开发创新CMR方法和应用于CAD和MCD的临床成像研究方面拥有良好的记录，包括NHLBI赞助的WISE研究。概述的K99阶段的指导计划包含了一个跨学科的计划，旨在为候选人提供深入但不可避免的广泛培训，以开发和应用定量心脏成像方法，并获得必要的技能过渡到一个独立的学术生涯在心脏成像领域。R00独立阶段的研究策略旨在系统地开发一种创新的伪影最小化CMR灌注成像方法，并进行试点患者研究，以获得有关所开发CMR方法有效性的初始数据，从而为随后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成像的主要技术挑战，并将使其能够可靠地检测受损的内膜下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.