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.

项目概要： 拟议研究的总体目标是开发、验证和应用创新磁共振 成像（MRI）生物标志物可用于提高我们对肌肉参与过程的理解 随着老化而发生的恶化。 MRI 不仅可以提供软组织解剖学的精美描述，而且 可以分析适当的 MRI 图像，以提供报告内在特征的定量参数图 组织成分、微观结构和功能的病理变化。我们建议开发新颖的 基于量化 R1ρ、自旋锁弛豫率及其随 锁定场振幅，我们称之为 R1ρ 色散成像。我们假设这种新颖的方法可以 用于量化微血管的退行性变化以及异常积累 肌纤维膜中的大分子。该提案的具体目标是完善和 实施 MRI 数据采集和分析的新方法，以得出基于 R1ρ 分散度并通过金标准验证其对病理生理变化的解释 方法包括组织学和成像质谱法。为了实现这些目标，我们将执行 啮齿类动物骨骼肌随衰老退化模型的纵向 MRI 成像研究。优化 然后，将在一组人类受试者中使用临床 3T MR 扫描仪对这些方法进行评估。定量 微血管变化以及大分子沉积的测量将为以下方面提供新的信息： 随着衰老而发生的特征变化的进展，并提供了可能催化新的新工具 改善组织变性影响的假设和治疗策略。 在这个职业发展奖期间，获奖者将获得老年病学、衰老生物学、 先进的 MRI 序列开发、组织学定量方法以及如何转化方法论 人类研究的创新。全面的教学培训和职业指导计划将提供 实现成为独立研究员的职业目标所需的知识和经验 在成像和衰老研究的界面。范德比尔特大学研究所的制度环境 成像科学非常出色，它将提供一个在以下领域打下坚实基础的典范机会： 开发用于转化应用的成像生物标志物。