4D SSFP MRI for Detecting Functionally Important Coronary Artery Stenosis at Rest

描述(申请人提供)：在美国，冠状动脉疾病是导致死亡的主要原因。据估计，美国有近700万人患有冠心病，每年约有50万人死于此病。最常见的冠心病会导致冠状动脉变窄(狭窄)，从而减少心肌的血流量和氧气供应。对这些功能损害的准确早期检测可能会使介入性血管重建术能够重新建立到受影响区域的血流。缺乏血运重建会增加心源性猝死的风险。目前还没有一种非侵入性的方法可以准确地检测由于CAD引起的区域血流差异。这项建议的广泛和长期目标是准确指导血运重建策略，并利用磁共振成像(MRI)监测冠状动脉疾病的治疗效果。我们提出了一种新的方法来检测临床上有意义的非血流限制性冠状动脉狭窄的存在(定义为冠状动脉管腔半径减少70%)。提出的方法依赖于心脏相分辨稳态自由进动(SSFP)磁共振(MR)信号的变化，该信号源于局部血容量和狭窄动脉供应的心肌区的氧合变化。与其他MRI方法相比，该方法的主要优点是，它可以在静息状态下检测到功能性显著的冠状动脉狭窄，从而消除了使用药物应激诱导剂评估冠状动脉灌注储备变化的需要。拟议的项目将分三个阶段进行：(1)第一阶段将包括技术开发，目标是开发一种自由呼吸的快速磁共振方法，以获取和评估整个心脏的心脏相依赖SSFP信号。(2)该项目的第二阶段将使用标准的磁共振方法，使用健康的犬模型独立地评估心肌血容量和氧合的时相变化。这一目标的主要目的是证明，在相同的犬模型中，可以使用SSFP成像同时检测血容量和氧合变化，并提高灵敏度。(3)我们建议的最后阶段将集中于评估急性冠状动脉狭窄动物模型中心脏时相分解的心肌血容量和氧合变化。这项研究的目的是证明SSFP方法在同时识别狭窄冠状动脉供应的心肌区域的血容量和氧合变化方面提供了更高的灵敏度。这些研究将为确定静息状态下人类是否存在明显的功能性冠状动脉狭窄提供基础。公共卫生相关性：一种准确和非侵入性的检测临床上有意义的冠状动脉疾病的方法可以为血运重建提供必要的动力，并防止心脏性猝死。这项提议提出了一种基于核磁共振的方法，它有可能彻底改变旨在检测临床上有意义的冠状动脉疾病的心脏检查的方式，这种检查在临床环境中进行，患者几乎不会感到不适。最重要的是，建议的方法有可能非侵入性地检测冠状动脉疾病，指导初步治疗，并使临床管理与疾病的患者群体。

DESCRIPTION (provided by applicant): Coronary artery disease is the leading cause of death in the United States. It is estimated that nearly 7 million people are living with coronary artery disease (CAD) in the US and about half a million people die from it each year. The most common form of CAD leads to narrowing of the coronary arteries (stenosis) resulting in reduced blood flow and oxygen supplied to the heart muscle. Accurate early detection of these functional impairments may permit interventional revascularization procedures to re-establish blood flow to the affected regions. The absence of revascularization increases the risk of sudden cardiac death. Currently there are no noninvasive methods that can accurately detect regional flow differences due to CAD. The broad and long term goal of this proposal is to accurately guide revascularization strategies and to monitor the efficacy of the treatment of coronary artery disease with magnetic resonance imaging (MRI). We propose a new method for detecting the presence of a clinically significant non flow-limiting coronary artery stenosis (defined as a decrease in coronary artery lumen radius by 70%). The proposed method relies on the use of cardiac phase-resolved steady-state free precession (SSFP) magnetic resonance (MR) signal changes originating from regional blood volume and oxygenation changes in the myocardial territory supplied by a stenotic artery. The principle advantage of this method over other MRI methods is that it can permit the detection of a functionally significant coronary stenosis under resting conditions, thereby eliminating the need to assess coronary perfusion reserve changes with pharmacological stress-inducing agents. The proposed project will be developed in three stages: (1) The first stage will consist of technical developments with the objective of developing a free-breathing, fast MR method for acquiring and evaluating cardiac phase-dependent SSFP signals over the whole heart. (2) The second stage of the project will use standard MR methods for evaluating phasic changes in myocardial blood volume and oxygenation independently using healthy canine models. The primary goal of this aim is to demonstrate that blood volume and oxygenation changes can be simultaneously detected with SSFP imaging in the same canine models with improved sensitivity. (3) The final stage of our proposal will focus on evaluating cardiac phase-resolved changes in myocardial blood volume and oxygenation in animal models with acute coronary stenosis. The goal of this study will be to demonstrate that the SSFP method provides enhanced sensitivity for simultaneously identifying changes in blood volume and oxygenation in a myocardial territory supplied by a stenotic coronary artery. These studies will provide the basis for identifying the presence of a functionally significant coronary stenosis in humans under resting conditions. PUBLIC HEALTH RELEVANCE: An accurate and noninvasive method for detecting clinically significant coronary artery disease can provide the necessary impetus for revascularization and prevent sudden cardiac deaths. This proposal presents a MRI-based method that has the potential to revolutionize the way cardiac exams aimed at detecting clinically significant coronary artery disease are performed in clinical settings with little or no patient discomfort. Most importantly, the proposed method has the potential to non-invasively detect coronary artery disease, guide initial treatment, and enable clinical management in patient populations with the disease.