Quantification of Regional Myocardial Oxygenation by MRI

描述(由申请人提供)： 在工业化国家，冠状动脉疾病(CAD)是主要的死亡原因。在正常生理条件下，心肌血流量、氧耗(MVO2)、心肌血容量与心肌机械功能密切相关。冠心病主要表现为心肌氧供需失衡。心肌氧摄取分数(OEF)和MVO2直接反映心肌氧供需平衡。准确评估心肌缺血状态，尤其是存活心肌，对于选择可能受益于冠状动脉血运重建术的患者至关重要。然而，在心肌中检测这种状态仍然是一个重要的临床问题，部分原因是在体内直接测量OEF和MVO2的固有困难，特别是在非侵入性和区域性的基础上。在这项提议中，假设心肌OEF和MVO2可以利用无创性磁共振成像(MRI)技术和BOLD(血氧水平依赖)效应来量化。后者以横向松弛时间T2对比度为特征。因此，我们的总体目标是优化和验证一系列临床可行的MRI技术，以可靠和一致地测量心肌OEF和MVO2。MVO2的测量基于皮克定律：MVO2与心肌OEF和血流量的乘积成正比。为了通过侵入性方法验证所提出的技术，我们建议使用闭胸犬模型。申请的目标将通过追求以下三个具体目标来实现。在目标1中，将通过建立数学模型来进一步优化首次通过灌注法。这种核磁共振方法将被用来测量静息和药物诱导的应激状态下的心肌血流量和容量。准确度将通过与金标准进行比较来确定，例如用于血流测量的微球和用于测量血容量的99mTc标记的红细胞。在目标2中，已建立的测量心肌OEF的技术将进一步优化并在体内得到验证。黄金标准将是同时从动脉和冠状静脉窦采血。这些优化的技术将被整合到Aim 3中，以计算有和没有冠状动脉狭窄、安静和药物应激时的心肌OEF和MVO2。验证将通过与PET成像进行比较来执行。这项MRI研究将为更好地了解心肌缺血和存活背后的生理学和病理生理学提供重要工具。此外，这一直接测量可能为评估心脏治疗的疗效提供了一种客观和方便的手段。最终，建议的方法可能有助于对CAD和其他心脏疾病进行更全面的MRI评估。

DESCRIPTION (provided by applicant): Coronary artery disease (CAD) is the leading cause of death in industrialized nations. Under normal physiological conditions, myocardial blood flow, oxygen consumption (MVO2), myocardial blood volume, and myocardial mechanical function are intimately related. CAD manifests as imbalances between myocardial oxygen supply and demand. Myocardial oxygen extraction fraction (OEF) and MVO2 directly reflects the balance of oxygen supply and demand of myocardium. Accurate assessment of myocardial ischemic status, particularly myocardial viability, is of paramount importance for selection of patients likely to benefit from coronary revascularization. However, detection of this status in myocardium remains an important clinical problem, partially owning to the inherent difficulty of direct measurement of OEF and MVO2 in vivo, particularly on a non-invasive and regional basis. In this proposal, it is hypothesized that myocardial OEF and MVO2 can be quantified using non-invasive magnetic resonance imaging (MRI) techniques and the BOLD (Blood Oxygen Level Dependent) effect. The later can be characterized by transverse relaxation time T2 contrast in MRI. Therefore, our overall objective is to optimize and validate a series of clinically viable MRI techniques to measure myocardial OEF and MVO2 reliably and consistently. Measurement of MVO2 is based on Pick's law: MVO2 is proportional to the product of myocardial OEF and blood flow. To validate the proposed techniques by invasive methods, we propose to use a closed-chest canine model. The goal of the application will be accomplished by pursuing the following three specific aims. In Aim 1, a first-pass perfusion method will be further optimized with an established mathematical modeling. This MRI method will be used to measure myocardial blood flow and volume at rest and during pharmacologically induced stress. Accuracy will be determined by comparing with gold standards such as microsphere for blood flow measurements and 99mTc-labeled red blood cells for blood volume measurement. In Aim 2, established techniques for measuring myocardial OEF will be further optimized and validated in vivo. The gold standard will be simultaneous blood sampling from artery and coronary sinus. These optimized techniques will be integrated in Aim 3 to calculate myocardial OEF and MVO2 in dogs with and without coronary artery stenosis, at rest and during pharmacological stress. Validation will be performed by comparison to PET imaging. This MRI research will provide an important tool for better understanding the physiology and pathophysiology underlying the myocardial ischemia and viability. In addition, this direct measurement may offer an objective and convenient means to assess the efficacy of cardiac therapies. Ultimately, the proposed methods may facilitate more comprehensive MRI assessments of CAD and other cardiac diseases.