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）是工业化国家死亡的主要原因。在正常的生理条件下，心肌流动，氧气消耗（MVO2），心肌血容量和心肌机械功能密切相关。 CAD表现为心肌氧和需求之间的不平衡。心肌氧提取分数（OEF）和MVO2直接反映了心肌的氧气供应和需求的平衡。准确评估心肌缺血状态，尤其是心肌生存力，对于选择可能受益于冠状动脉血运重建的患者至关重要。但是，对心肌中这种状态的检测仍然是一个重要的临床问题，部分拥有在体内直接测量OEF和MVO2的固有难度，尤其是在非侵入性和区域基础上。在此提案中，可以假设可以使用非侵入性磁共振成像（MRI）技术和粗体（血氧水平依赖性）效应来定量心肌OEF和MVO2。后来的特征是MRI中的横向松弛时间T2对比。因此，我们的总体目标是优化和验证一系列临床上可行的MRI技术，以可靠，一致地测量心肌OEF和MVO2。 MVO2的测量基于PICS的定律：MVO2与心肌OEF和血流的产物成正比。为了通过侵入性方法验证提出的技术，我们建议使用闭胸犬模型。应用程序的目标将通过追求以下三个特定目标来实现。在AIM 1中，将通过既定的数学建模将进一步优化第一频繁的灌注方法。该MRI方法将用于测量静止和药理诱导应激期间的心肌流动和体积。精度将通过与金标准品（例如用于血流测量值的微球和99mtc标记的红细胞进行血液体积测量）进行比较。在AIM 2中，将在体内进一步优化和验证测量心肌OEF的既定技术。黄金标准将是从动脉和冠状窦同时进行血液采样。这些优化的技术将集成到AIM 3中，以计算有和没有冠状动脉狭窄的狗的心肌OEF和MVO2，在静止和药理学胁迫下。验证将与PET成像进行比较。这项MRI研究将为您更好地理解心肌缺血和生存能力的生理和病理生理学提供重要的工具。此外，这种直接测量可能会提供一种客观和方便的手段来评估心脏疗法的功效。最终，提出的方法可能有助于对CAD和其他心脏病进行更全面的MRI评估。