Development and Application of T1rho Dispersion Imaging of Aging Muscle

衰老肌肉T1rho色散成像的开发与应用

• 批准号: 10629331
• 负责人: Fatemeh Adelnia
• 金额: $ 11.95万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10629331
• 关键词: 3-Dimensional; Adult; Age; Aging; Anatomy; Animal Model; Animals; Biological; Biological Markers; Biology of Aging; Blood Vessels; Blood Volume; Blood capillaries; Capillarity; Cells; Characteristics; Chronic Disease; Clinical; Clinical Research; Collagen; Data; Data Analyses; Deposition; Deterioration; Development; Elderly; Environment; Etiology; Extracellular Matrix; Fatty acid glycerol esters; Fibrosis; Foundations; Goals; Histologic; Histology; Human; Image; Imaging Techniques; Impairment; Inbred F344 Rats; Institution; K-Series Research Career Programs; Knowledge; Magnetic Resonance Imaging; Maps; Mass Spectrum Analysis; Measurement; Measures; Membrane; Mentorship; Metabolic; Methodology; Methods; Muscle; Muscle Contraction; Muscle Fibers; Muscular Atrophy; Noise; Nutrient; Oxygen; Pathologic; Pathology; Patient Self-Report; Physical activity; Process; Protocols documentation; Relaxation; Reporting; Research; Research Personnel; Resolution; Rest; Rodent Model; Role; Rotation; Scanning; Signal Transduction; Skeletal Muscle; Structure; Surrogate Markers; Techniques; Therapeutic; Thigh structure; Time; Tissues; Training; Translating; Universities; Validation; Variant; Water; age group; age related; animal old age; career; career development; clinical application; clinical implementation; cohort; data acquisition; diffusion weighted; digital pathology; disability; experience; frailty; functional disability; hemodynamics; human subject; imaging biomarker; imaging modality; imaging science; imaging study; improved; indexing; innovation; interest; juvenile animal; macromolecule; magnetic resonance imaging biomarker; microvascular pathology; middle age; mitochondrial dysfunction; muscle aging; novel; parametric imaging; programs; protein distribution; quadriceps muscle; sarcopenia; simulation; soft tissue; time interval; tissue degeneration; tool; translational applications; walking speed

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.

项目摘要： 该研究的总体目标是开发、验证和应用创新的磁共振技术。 成像（MRI）生物标志物，可用于提高我们对肌肉参与的过程的理解 随着年龄的增长而发生的退化。MRI不仅可以提供对软组织解剖的极好描述， 可以分析适当的MRI图像以提供定量参数图， 组织组成、微观结构和功能的病理变化。我们建议开发新的 参数图像的基础上量化的变化R1ρ，自旋锁弛豫率，其变化与 锁定场振幅，我们称之为R1ρ色散成像。我们假设这种新的方法可以 用于量化微血管系统的退行性变化以及 肌肉纤维膜中的大分子。这项建议的具体目标是改进和 实现MRI数据采集和分析新方法以基于 并通过金标准验证其在病理生理变化方面的解释 方法包括组织学和成像质谱。为了实现这些目标，我们将 骨骼肌老化的啮齿动物模型的纵向MRI成像研究。优化 然后在临床3T MR扫描仪上在一组人类受试者中评估方法。定量 测量微血管变化沿着的大分子沉积将提供关于 随着年龄的增长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 假设和治疗策略，以改善组织变性的影响。 在这个职业发展奖期间，获奖者将获得老年医学，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 人类研究的创新。一个全面的教学培训和职业导师计划将提供 完成成为独立研究人员的职业目标所需的知识和经验 在影像学和衰老研究的界面上。范德比尔特大学研究所的制度环境 成像科学是特殊的，将提供一个示范性的机会，建立一个坚实的基础， 开发用于翻译应用的成像生物标志物。