Nuclear Magnetic Tirho Relaxation in Acute and Chronic Myocardial Infarctions

项目摘要 心脏左室重构每年导致美国超过25万人死于心力衰竭 各州。心肌梗死扩大、进行性变薄和非收缩纤维组织沉积可以 导致非缺血交界区节段代偿性扩张。最终，心输出量不能 在这种渐进式心脏扩大的情况下得以维持。项目的长期目标是以非侵入性方式 应用磁共振成像技术检测心肌梗死水肿、纤维化和心肌梗死稳定性 基于核磁弛豫产生的内源性1H对比度。我们的假设是 心肌梗死后8周内发生的原发生物学改变，尤其是 心肌细胞的凋亡、细胞因子的募集和纤维性瘢痕组织的沉积对 水分子中1H核的磁环境。1H磁环境的变化可以是 使用Witschey博士开发的新的T1ρ磁共振成像技术在 研究生院。1H T1ρ弛豫对水分子的低频涨落很敏感 低交换条件下自由水1HS与蛋白质和大分子的总表观交换率 总的水流动性的频率和变化。在对猪进行的初步研究中，T1ρ是 显示为检测由旋转引起的总体表观汇率和松弛速率的变化 结扎第二和第三节后8周磁偶极-偶极相互作用的调制 旋支动脉的分支。这些发现提供了一个机会，可以克服当前 基于T2松弛测量的内源性增强MRI方法。在这项提案中，研究将是 开发克服磁场异质性(静电场和射频场)和运动的方法 与T1ρ心脏成像相关的伪影。在独立阶段，实验将被 进行以(1)连续考察表观1H汇率和旋转调制的影响 磁偶极-偶极耦合对脑缺血后1H-T1ρ弛豫时间的影响 猪心脏重塑时间延长至8周，以及(2)确定1H-T1ρ方法是否提供不同 来自基于灌注的核磁共振技术的生物化学信息。广泛的额外培训是 在K99阶段提出，包括授课培训、参加会议、研讨会和 讲习班、职业发展委员会一年两次的会议，以及关于创造 心功能不全的动物模型，最新的成像和技术开发，分析和 研究职业技能的发展。这项培训将为Witschey博士实现他的职业目标做好准备 通过新的跨学科技术促进我们对心脏病的理解和治疗 与基础科学研究相结合。

Project Summary Cardiac left ventricular remodeling is responsible for over 250,000 heart failure deaths each year in the United States. Myocardial infarct expansion, progressive thinning and deposition of non-contractile fibrotic tissue can result in compensatory dilatation of the nonischemic borderzone segments. Ultimately, cardiac output cannot be sustained under such progressive heart enlargement. The long term project goals are to noninvasively detect myocardial infarction edema, fibrosis and infarct stability using magnetic resonance imaging techniques based on endogenous 1H contrast generated by nuclear magnetic relaxation. The hypothesis is that the primary biological changes occurring within the first 8 weeks following myocardial infarction, particularly myocyte apoptosis, recruitment of cytokines and deposition of fibrotic scar tissue, have a significant effect on the magnetic environment of 1H nuclei in water molecules. The 1H magnetic environment changes can be detected using novel T1ρ magnetic resonance imaging (MRI) techniques developed by Dr. Witschey during graduate school. 1H T1ρ relaxation is sensitive to low frequency fluctuations of water molecules including the overall apparent exchange rate between free water 1Hs and proteins and macromolecules at low exchange frequencies and changes in total water mobility. In preliminary investigations performed on swine, T1ρ was shown to detect changes to the overall apparent exchange rate and rate of relaxation caused by rotational modulation of the magnetic dipole-dipole interaction at 8 weeks following ligation of the second and third branches of the circumflex artery. These findings present an opportunity to overcome limitations of current methods of endogenous contrast MRI based on T2 relaxation measurements. In this proposal, research will be performed to develop methods to overcome magnetic field heterogeneity (static and RF fields) and motion artifacts associated specifically with T1ρ cardiac imaging. During the independent phase, experiments will be carried out to (1) serially examine the effect of apparent 1H exchange rates and rotational modulation of magnetic dipole-dipole coupling on 1H T1ρ relaxation times from the moment of initial ischemia throughout the period of cardiac remodeling to 8 weeks in swine and (2) determine whether 1H T1ρ methods provide different information regarding biochemistry from perfusion based MRI techniques. Extensive additional training is proposed during the K99 phase to include didactic training, participation at conferences, seminars and workshops, biannual meetings of a career development committee, and hands-on training in the creation of animals models of cardiac dysfunction, state-of-the-art imaging and technique development, analysis, and development of research career skills. This training will prepare Dr. Witschey to achieve his career goals to advance our understanding and treatment of cardiac disease through novel and interdisciplinary techniques combined with basic science research.