Development and Application of T1rho Dispersion Imaging of Aging Muscle

项目总结： 提出的研究的总体目标是开发、验证和应用创新的磁共振 可用于提高我们对肌肉相关过程的理解的成像(MRI)生物标志物 随着年龄的增长而发生的退化。核磁共振不仅可以提供对软组织解剖的精湛描述，而且 可以分析适当的MRI图像以提供报告内在的定量参数图 组织成分、微结构和功能的病理变化。我们计划开发新的 基于量化R1ρ、自旋锁弛豫速率及其随时间的变化的参数图像 锁定场幅度，我们称之为R1ρ色散成像。我们假设这种新的方法论可以是 用于量化微血管的退行性变化以及血管的异常堆积 肌纤维膜中的大分子。这项提案的具体目标是完善和 实现MRI数据采集和分析的新方法，以基于 关于R1ρ的离散度，并通过金标准验证其在病理生理变化方面的解释 方法包括组织学、成像质谱学。为了实现这些目标，我们将履行 骨骼肌随增龄退化啮齿动物模型的纵向mri成像研究。已优化 然后将在临床3T磁共振扫描仪上对一组人类受试者的方法进行评估。量化的 随着大分子沉积的微血管变化的测量将提供关于 随着老化而发生的特征变化的进展，并提供了一种新的工具，可以催化新的 改善组织退变影响的假说和治疗策略。 在这一职业发展奖期间，获奖者将获得老年学、衰老生物学、 先进的MRI序列开发，组织学的定量方法，以及如何翻译方法学 人类研究的创新。一个全面的教学培训和职业指导计划将提供 完成成为一名独立研究员的职业目标所需的知识和经验 在影像与衰老研究的交界处。范德比尔特大学学院的制度环境 成像科学是独一无二的，将提供一个示范机会，在 为翻译应用开发成像生物标记物。

Project Summary: The overall goals of the research proposed are to develop, validate and apply innovative magnetic resonance imaging (MRI) biomarkers that can be used to improve our understanding of the processes involved in muscle deterioration that occurs with aging. MRI can provide not only superb depiction of soft tissue anatomy, but appropriate MRI images can be analyzed to provide quantitative parametric maps that report intrinsic pathological changes in tissue composition, microstructure, and function. We propose to develop novel parametric images based on quantifying changes in R1ρ, the spin-lock relaxation rate, and its variation with the locking field amplitude, which we term R1ρ dispersion imaging. We hypothesize this novel methodology can be used to quantify degenerative changes in microvasculature as well as the abnormal accumulation of macromolecules in the membranes of muscle fiber. The specific aims of this proposal are to refine and implement novel methods of MRI data acquisition and analysis to derive quantitative parametric images based on R1ρ dispersion and validate their interpretation in terms of pathophysiological changes via gold-standard methods including histology, and imaging mass spectroscopy. To achieve these goals, we will perform longitudinal MRI imaging studies of rodent models of skeletal muscle deterioration with aging. Optimized methods will then be evaluated in a cohort of human subjects on a clinical 3T MR scanner. The quantitative measures of microvascular changes along with macromolecular deposition will provide new information on the progression of the characteristic changes that occur with aging and provide a new tool that may catalyze new hypotheses and therapeutic strategies to ameliorate the effects of tissue degeneration. During this career development award, the awardee will gain crucial training in geriatric, the biology of aging, advanced MRI sequence development, quantitative methods of histology, and how to translate methodological innovations into human studies. A comprehensive didactic training and career mentorship program will provide the knowledge and experiences needed to accomplish the career goal of becoming an independent researcher at the interface of imaging and aging study. The institutional environment at Vanderbilt University Institute of Imaging Science is exceptional and will provide an exemplary opportunity to build a strong foundation in developing imaging biomarkers for translational applications.