Nuclear magnetic Tirho relaxation in acute and chronic myocardial infarctions

描述(由申请人提供)：在美国，心脏左心室重构每年导致超过25万人死于心力衰竭。心肌梗死扩大、进行性变薄和非收缩纤维组织沉积可导致非缺血交界区节段的代偿性扩张。最终，在这种渐进性心脏增大的情况下，心输出量是无法维持的。该项目的长期目标是使用核磁共振成像技术，基于核磁松弛产生的内源性1H对比，无创地检测心肌梗死的水肿、纤维化和心肌梗死稳定性。假设心肌梗死后8周内发生的主要生物学变化，特别是心肌细胞的凋亡、细胞因子的募集和纤维化瘢痕组织的沉积，对水分子中1H核的磁环境有显著的影响。1H磁环境的变化可以使用Witschey博士在研究生期间开发的新的T1a磁共振成像(MRI)技术来检测。1HT1a弛豫对水分子的低频波动很敏感，包括自由水1HS与蛋白质和大分子在低交换频率下的总表观交换率以及总水流动性的变化。在猪身上进行的初步研究表明，在结扎回旋动脉第二和第三支后8周，T1a检测到由于磁偶极-偶极相互作用的旋转调制而引起的总体表观汇率和松弛速率的变化。这些发现为克服目前基于T2松弛测量的内源性对比磁共振成像方法的局限性提供了机会。在这项提案中，将开展研究以开发克服磁场异质性(静电场和射频场)和运动伪影的方法，这些伪影特别与T1a心脏成像相关。在独立阶段，将进行以下实验：(1)连续检测1H交换率和磁偶极-偶极耦合的旋转调制对从猪心脏重塑期间的初始缺血时刻到8周的1H-T1a松弛时间的影响；(2)确定1H-T1a方法是否提供了与基于灌注的MRI技术不同的生化信息。建议在K99阶段进行广泛的额外培训，包括授课培训、参加会议、研讨会和研讨会、职业发展委员会一年两次的会议，以及在创建心功能障碍动物模型、最先进的成像和技术开发、分析和研究职业技能发展方面的实践培训。这次培训将为Witschey博士实现他的职业目标做好准备，他将通过与基础科学研究相结合的新的跨学科技术来促进我们对心脏病的理解和治疗。

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.