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: 9035421
• 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 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9035421
• 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; Professional Competence; 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; 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 心脏左心室重塑每年造成25万多人的心力衰竭死亡 国家。心肌梗塞的扩张，非取包纤维化组织的进行性稀疏和沉积可以 导致非缺血性边界区段的补偿性扩张。最终，心输出不能 在这种渐进的心脏扩张下维持。长期项目目标是无创 使用磁共振成像技术检测心肌梗死水肿，纤维化和梗塞稳定性 基于核磁松弛产生的内源性对比度。假设是 心肌梗塞后的前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1小时核的磁环境。 1H磁性环境的变化可以是 使用新颖的T1ρ磁共振成像（MRI）技术检测到Witschey博士在 研究所。 1HT1ρ弛豫对水分子的低频波动敏感 在低汇率下，自由水1HS和蛋白质和大分子之间的总体表观汇率 频率和总水迁移的变化。在对猪进行的初步调查中，T1ρ是 显示可检测到由旋转引起的总体表观汇率和放松率的变化 第二和第三 环绕动脉的分支。这些发现为克服当前的局限性提供了机会 基于T2松弛测量值的内源性对比度MRI方法。在该建议中，研究将是 执行以开发克服磁场异质性（静态和RF场）和运动的方法 与T1ρ心脏成像有关的伪影。在独立阶段，实验将是 进行（1）串行检查表观1H汇率和旋转调制的影响 从初始缺血的时刻开始，磁性偶极偶极偶联在1HT1ρ放松时间上 心脏重塑期至猪的8周，（2）确定1HT1ρ方法是否提供不同 来自基于灌注的MRI技术的生物化学的信息。广泛的额外培训是 在K99阶段提出的，包括教学培训，参加会议，半小伙子和 讲习班，职业发展委员会的双年展会议以及创建的动手培训 心脏功能障碍，最先进的成像和技术开发，分析和分析的动物模型 研究职业技能的发展。这项培训将使Witschey博士为实现自己的职业目标做好准备 通过新颖和跨学科技术来提高我们对心脏病的理解和治疗 结合基础科学研究。

项目成果

Image reconstruction in k-space from MR data encoded with ambiguous gradient fields.

• DOI: 10.1002/mrm.25152
• 发表时间: 2015-02
• 期刊: Magnetic resonance in medicine
• 影响因子: 3.3
• 作者: Schultz G;Gallichan D;Weber H;Witschey WR;Honal M;Hennig J;Zaitsev M
• 通讯作者: Zaitsev M