Nuclear magnetic Tirho relaxation in acute and chronic myocardial infarctions

描述（由申请人提供）：在美国，心脏左心室重塑导致每年超过250，000例心力衰竭死亡。心肌梗死范围扩大、进行性变薄和非收缩性纤维化组织沉积可导致非缺血性边缘区节段代偿性扩张。最终，在这种进行性心脏增大的情况下，心输出量不能维持。长期项目目标是使用基于核磁弛豫产生的内源性1H对比度的磁共振成像技术无创检测心肌梗死水肿、纤维化和梗死稳定性。该假说认为，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瘢痕组织的沉积，对水分子中1H核的磁环境有显著影响。1H磁环境的变化可以使用Witschey博士在研究生期间开发的新型T1 A磁共振成像（MRI）技术来检测。1H T1 A弛豫对水分子的低频波动敏感，包括在低交换频率下游离水1H与蛋白质和大分子之间的总表观交换速率以及总水迁移率的变化。在对猪进行的初步研究中，T1 A显示出在结扎旋动脉的第二和第三分支后8周检测由磁偶极-偶极相互作用的旋转调制引起的总体表观交换率和弛豫率的变化。这些发现提供了一个机会，以克服目前的内源性对比MRI的T2弛豫测量的基础上的方法的局限性。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T1 A心脏成像相关的运动伪影的方法。在独立阶段，将进行实验以（1）在猪中连续地检查从初始缺血的时刻到整个心脏重构的8周期间，表观1H交换率和磁偶极-偶极耦合的旋转调制对1HT 1A弛豫时间的影响，和（2）确定1H T1 A方法是否提供了与基于灌注的MRI技术不同的生物化学信息。在K99阶段提出了广泛的额外培训，包括教学培训，参加会议，研讨会和讲习班，职业发展委员会的半年期会议，以及创建心脏功能障碍动物模型的实践培训，最先进的成像和技术开发，分析和研究职业技能的发展。这项培训将使Witschey博士做好准备，以实现他的职业目标，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。

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.