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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要在美国，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可发生扩张、进行性变薄和非收缩性纤维化组织的沉积。导致非缺血性边界区节段的代偿性扩张，最终导致心输出量下降。在这种渐进性心脏扩大的情况下维持下去，长期项目目标是非侵入性的。使用磁共振成像技术检测心肌梗塞水肿、纤维化和梗塞稳定性基于核磁弛豫产生的内源 1H 对比度的假设是心肌梗塞后前 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 原子核的磁环境 1H 磁环境的变化可表示为使用 Witchey 博士在期间开发的新型 T1ρ 磁共振成像 (MRI) 技术检测到 1H T1ρ 弛豫对水分子的低频波动敏感，包括低交换时游离水 1Hs 与蛋白质和大分子之间的总体表观交换率在对猪进行的初步调查中，T1ρ 为总水流动性的频率和变化。用于检测由旋转引起的总体表观汇率和松弛率的变化第二次和第三次结扎后 8 周时磁偶极子-偶极子相互作用的调节这些发现为克服当前的局限性提供了机会。基于 T2 弛豫测量的内源性对比 MRI 方法在本提案中将进行研究。开发克服磁场不均匀性（静态和射频场）和运动的方法与 T1ρ 心脏成像相关的伪影在独立阶段，将进行实验。 (1) 连续检验表观 1H 汇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，从初始缺血时刻到整个过程猪心脏重塑期长达 8 周，并 (2) 确定 1H T1ρ 方法是否提供不同的结果基于灌注的 MRI 技术提供有关生物化学的信息。 K99 阶段建议包括教学培训、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、最先进的成像和技术开发、分析和该培训将为 Witschey 博士实现他的职业目标做好准备。通过新颖的跨学科技术，我们对心脏病的理解和治疗不断进步与基础科学研究相结合。