Quantification of Regional Myocardial Oxygenation by MRI

通过 MRI 量化局部心肌氧合

• 批准号: 7017709
• 负责人: JIE ZHENG
• 金额: $ 36.4万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7017709
• 关键词: artery stenosis; bioimaging /biomedical imaging; blood flow measurement; blood volume; coronary artery; disease /disorder model; dogs; heart disorder diagnosis; heart imaging /visualization /scanning; magnetic resonance imaging; mathematical model; method development; myocardial ischemia /hypoxia; oxygen consumption; perfusion; positron emission tomography; radiotracer

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.

描述（由申请人提供）： 冠状动脉疾病（CAD）是工业化国家的主要死亡原因。在正常生理条件下，心肌血流量、耗氧量（MVO 2）、心肌血容量和心肌机械功能密切相关。CAD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，特别是心肌存活性，对于选择可能受益于冠状动脉血运重建的患者至关重要。然而，心肌中这种状态的检测仍然是一个重要的临床问题，部分原因是直接测量体内OEF和MVO2的固有困难，特别是在非侵入性和区域性基础上。在该提案中，假设心肌OEF和MVO2可以使用无创磁共振成像（MRI）技术和BOLD（血氧水平依赖性）效应进行定量。后者可通过MRI横向弛豫时间T2对比来表征。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的测量基于匹克定律：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，将利用已建立的数学建模进一步优化首过灌注方法。该MRI方法将用于测量静息时和运动诱导应激期间的心肌血流量和体积。将通过与金标准品（如用于血流量测量的微球和用于血容量测量的99mTc标记红细胞）进行比较来确定准确度。在目标2中，将在体内进一步优化和验证用于测量心肌OEF的已建立技术。金标准将是同时从动脉和冠状窦采集血液样本。这些优化技术将整合到目标3中，以计算静息和药理学应激期间有和无冠状动脉狭窄犬的心肌OEF和MVO2。将通过与PET成像进行比较进行确认。这项MRI研究将为更好地了解心肌缺血和存活的生理学和病理生理学提供重要的工具。此外，这种直接测量可以提供客观和方便的手段来评估心脏治疗的疗效。最终，所提出的方法可能有助于CAD和其他心脏疾病的更全面的MRI评估。