Nuclear Magnetic Tirho Relaxation in Acute and Chronic Myocardial Infarctions

核磁 Tirho 舒张治疗急性和慢性心肌梗塞

• 批准号: 8843526
• 负责人: Walter R.T. Witschey
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-01-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8843526
• 关键词: Acute; Animal Model; Animals; Apoptosis; Arteries; Basic Science; Biochemical; Biochemistry; Biological; Blood; Cardiac; Cardiac Output; Cardiomegaly; Cell Nucleus; Cells; Cessation of life; Chemicals; Chronic; Cicatrix; Collagen; Contrast Media; Coupling; Deposition; Dilatation - action; Edema; Educational workshop; Environment; Family suidae; Fibrosis; Frequencies; Gadolinium; Goals; Heart; Heart Diseases; Heart failure; Heterogeneity; Image; Imaging Techniques; Infarction; Intervention; Investigation; Ischemia; Kidney Failure; Left; Left Ventricular Remodeling; Ligation; Linear Regressions; Magnetic Resonance Imaging; Magnetism; Measurement; Measures; Methods; Monitor; Morphologic artifacts; Motion; Muscle Cells; Myocardial; Myocardial Infarction; Myocardial dysfunction; Nuclear; Optics; Patients; Performance; Perfusion; Phase; Physiologic pulse; Process; Proteins; Relaxation; Research; Research Proposals; Schools; Signal Transduction; Techniques; Testing; Time; Tissues; Training; Treatment Efficacy; United States; Variant; Ventricular; Water; Weight; base; cardiovascular visualization; career; career development; crosslink; cytokine; density; gadolinium oxide; in vivo; macromolecule; magnetic dipole; magnetic field; meetings; novel; novel strategies; operation; outcome forecast; programs; research and development; research study; response; rho; skills; symposium; technique development; water environment

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.

项目摘要 在美国，心脏左心室重构导致每年超过25万例心力衰竭死亡。 States.心肌梗死范围扩大、进行性变薄和非收缩性纤维化组织的沉积， 导致非缺血边缘区节段的代偿性扩张。最终，心输出量不能 在这种渐进的心脏扩大下维持。长期项目目标是以非侵入性方式 使用磁共振成像技术检测心肌梗死水肿、纤维化和梗死稳定性 基于由核磁弛豫产生的内源性1H对比度。假设是， 心肌梗死后前8周内发生的主要生物学变化，特别是 肌细胞凋亡、细胞因子的募集和纤维化瘢痕组织的沉积，对 水分子中氢原子核的磁环境。1H磁环境的变化可以 使用Witschey博士在1999年开发的新型T1ρ磁共振成像（MRI）技术检测到 研究生院1H T1ρ弛豫对水分子的低频波动敏感，包括 低交换时游离水~ 1H与蛋白质和大分子之间的总表观交换速率 频率和总水流动性的变化。在对猪进行的初步研究中， 显示检测由旋转引起的总体表观汇率和松弛率的变化 在第二和第三磁偶极-偶极相互作用的连接后8周， 旋动脉的分支这些发现提供了一个机会，以克服目前的局限性， 基于T2弛豫测量的内源性对比MRI方法。在这项研究中，将 进行开发方法，以克服磁场异质性（静态和射频场）和运动 与T1ρ心脏成像相关的伪影。在独立阶段，实验将 进行了（1）连续检查表观1H交换率和旋转调制的影响， 磁偶极-偶极耦合对1H T1ρ弛豫时间的影响，从初始缺血的那一刻起， 猪心脏重塑期至8周;（2）确定1H T1ρ方法是否提供不同的结果 基于灌注的MRI技术的生物化学信息。广泛的额外培训是 建议在K99阶段，包括教学培训，参加会议，研讨会， 讲习班、职业发展委员会半年一次的会议，以及关于建立 心功能不全的动物模型，最先进的成像和技术开发，分析， 发展研究职业技能。这项培训将为Witschey博士实现其职业目标做好准备， 通过新的跨学科技术来促进我们对心脏病的理解和治疗 结合基础科学研究。