Quantitative assessment of early structural and functional changes in aging skeletal muscle

衰老骨骼肌早期结构和功能变化的定量评估

• 批准号: 10409734
• 负责人: Valentina Mazzoli
• 金额: $ 10.3万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10409734
• 关键词: Address; Affect; Age; Aging; Architecture; Atrophic; Biological Markers; Biology; Biomechanics; Biopsy; Caring; Cause of Death; Cell Size; Clinical; Clinical Research; Collagen; Communities; Deposition; Detection; Development; Diffusion Magnetic Resonance Imaging; Disease; Early Diagnosis; Early identification; Elderly; Evaluation; Exercise; Fatty acid glycerol esters; Fiber; Fibrosis; Goals; Gold; Health; Healthcare; Histologic; Human; Image; Imaging Device; Imaging Techniques; Individual; Infiltration; Inflammation; Intervention; Lead; Length; Longitudinal Studies; Lower Extremity; Magnetic Resonance Imaging; Maps; Measurement; Measures; Medical; Methods; Monitor; Morbidity - disease rate; Muscle; Muscle Cells; Muscle Fibers; Muscle function; Muscular Atrophy; Musculoskeletal; Myopathy; Outcome; Pathogenesis; Pathologic; Patients; Physical Function; Physical Performance; Physical assessment; Physiologic pulse; Population; Protocols documentation; Radiology Specialty; Reproducibility; Research Personnel; Risk; Sensitivity and Specificity; Severity of illness; Skeletal Muscle; Syndrome; Tendon structure; Time; Tissues; Training; United States; Work; age related; aged; aging population; base; biomechanical model; biophysical model; clinical imaging; clinical research site; cohort; cost; disability; falls; follow-up; frailty; functional outcomes; functional status; high risk; imaging approach; imaging modality; improved; innovation; insight; magnetic resonance imaging biomarker; mortality; multidisciplinary; muscle form; muscle strength; non-invasive imaging; novel; novel imaging technique; novel therapeutics; oscillating gradient spin echo; preservation; sarcopenia; tool; vastus lateralis

Project Summary/Abstract Sarcopenia is a leading cause of death and disability for the aging population and creates a societal burden resulting in $18 billion in annual costs in the United States alone. While new treatments have shown promise to improve functional outcomes, they have been hampered by the lack of non-invasive biomarkers sensitive to the early stages of the disease. In particular, non-invasive assessment of muscle atrophy is a long-recognized but unmet need in the sarcopenia community, and we propose to use magnetic resonance imaging (MRI) to address this need. This project develops a clinically feasible toolset to noninvasively image early atrophic changes in skeletal muscle using Magnetic Resonance Imaging (MRI). Our specific aims are (1) to develop new MRI techniques that utilize a novel pulse sequence to quantify muscle cell size and changes thereof due to atrophy; (2) to validate MR atrophy imaging with histological evaluation of muscle biopsies from young and older subjects, and correlate with muscle strength; and (3) to apply MRI atrophy methods to study longitudinal changes in sarcopenic patients and in pre-frail subjects, which are at high risk of developing sarcopenia. The innovation of this work lies in the development of a novel imaging technique to quantify atrophy in muscle tissue non-invasively. The outcome of this proposal is a validated and quantitative MRI tool to image muscle quality, and its relationship to patient strength and functional status. The significance of this work is a robust clinical MRI protocol to image early degenerative changes associated to sarcopenia that is transferrable to any clinical site. The reproducible and robust tool will allow the sarcopenia imaging community to identify subject at risk, and implement targeted and timely interventions that can stop or slow the progression of sarcopenia.

项目概要/摘要 肌肉减少症是老年人口死亡和残疾的主要原因，并造成社会负担 仅在美国每年就造成 180 亿美元的成本。虽然新疗法已显示出希望 改善功能结果，但由于缺乏对功能敏感的非侵入性生物标志物而受到阻碍 疾病的早​​期阶段。特别是，肌肉萎缩的非侵入性评估是一种长期被认可但尚未被认可的方法。 肌肉减少症社区未满足的需求，我们建议使用磁共振成像 (MRI) 来解决 这个需要。 该项目开发了一种临床上可行的工具集，用于对骨骼的早期萎缩变化进行无创成像。 使用磁共振成像 (MRI) 来观察肌肉。我们的具体目标是 (1) 开发新的 MRI 技术 利用新颖的脉冲序列来量化肌肉细胞的大小及其由于萎缩而发生的变化； (2) 验证 MR 萎缩成像与年轻和老年受试者肌肉活检的组织学评估，并将 有肌肉力量； (3)应用MRI萎缩方法研究肌少症患者的纵向变化 以及体弱前的受试者，这些受试者患肌肉减少症的风险很高。 这项工作的创新在于开发了一种新颖的成像技术来量化肌肉萎缩 非侵入性地组织。该提案的成果是一种经过验证的定量 MRI 工具，用于对肌肉进行成像 质量及其与患者体力和功能状态的关系。这项工作的意义在于 临床 MRI 协议，用于对与肌肉减少症相关的早期退行性变化进行成像，这种变化可转移到任何 临床现场。可重复且强大的工具将使肌少症成像界能够识别受试者 风险，并实施有针对性的及时干预措施，以阻止或减缓肌肉减少症的进展。