Nuclear magnetic Tirho relaxation in acute and chronic myocardial infarctions

核磁 Tirho 弛豫在急性和慢性心肌梗死中的作用

• 批准号: 8242544
• 负责人: Walter R.T. Witschey
• 金额: $ 8.01万
• 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 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8242544
• 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; Functional disorder; 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; 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; career; career development; crosslink; cytokine; density; gadolinium oxide; in vivo; macromolecule; magnetic field; meetings; novel; novel strategies; operation; outcome forecast; programs; research and development; research study; response; rho; skills; symposium; technique development; water environment

DESCRIPTION (provided by applicant): 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 T1A magnetic resonance imaging (MRI) techniques developed by Dr. Witschey during graduate school. 1H T1A 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, T1A 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 T1A 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 T1A relaxation times from the moment of initial ischemia throughout the period of cardiac remodeling to 8 weeks in swine and (2) determine whether 1H T1A 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.

描述（由申请人提供）：在美国，心脏左心室重构每年导致超过 250,000 例心力衰竭死亡。心肌梗塞扩张、进行性变薄和非收缩性纤维化组织的沉积可导致非缺血性边界区节段的代偿性扩张。最终，在这种进行性心脏扩大的情况下，心输出量无法维持。长期项目目标是利用基于核磁弛豫产生的内源 1H 对比度的磁共振成像技术，无创地检测心肌梗塞水肿、纤维化和梗塞稳定性。该假设认为，心肌梗死后前 8 周内发生的主要生物学变化，特别是心肌细胞凋亡、细胞因子的募集和纤维化疤痕组织的沉积，对水分子中 1H 核的磁环境具有显着影响。 1H 磁环境变化可以使用 Witschey 博士在研究生期间开发的新型 T1A 磁共振成像 (MRI) 技术来检测。 1H T1A 弛豫对水分子的低频波动敏感，包括低交换频率下自由水 1H 与蛋白质和大分子之间的总体表观交换率以及总水迁移率的变化。在对猪进行的初步研究中，T1A 可以检测到结扎回旋动脉第二和第三分支后 8 周时由磁偶极子-偶极子相互作用的旋转调制引起的总体表观交换率和松弛率的变化。这些发现为克服当前基于 T2 弛豫测量的内源性对比 MRI 方法的局限性提供了机会。在本提案中，将进行研究以开发克服磁场异质性（静态和射频场）和与 T1A 心脏成像相关的运动伪影的方法。在独立阶段，实验将进行（1）连续检查表观 1H 交换率和磁偶极子-偶极子耦合的旋转调制对 1H T1A 弛豫时间的影响，从初始缺血时刻到心脏重塑期间。在猪中进行 8 周，(2) 确定 1H T1A 方法是否提供与基于灌注的 MRI 技术不同的生物化学信息。建议在 K99 阶段进行广泛的额外培训，包括教学培训、参加会议、研讨会和讲习班、职业发展委员会每两年一次的会议，以及创建心功能障碍动物模型、最新研究进展的实践培训。 -艺术成像和技术开发、分析和研究职业技能的发展。此次培训将为 Witschey 博士实现他的职业目标做好准备，即通过新颖的跨学科技术与基础科学研究相结合，促进我们对心脏病的理解和治疗。