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

项目总结/摘要 肌肉减少症是老龄人口死亡和残疾的主要原因，并造成社会负担 仅在美国，每年的成本就高达180亿美元。虽然新的治疗方法显示出希望， 改善功能结果，他们一直受到缺乏非侵入性生物标志物敏感的， 疾病的早期阶段。特别是，肌肉萎缩的非侵入性评估是长期公认的，但 未满足的需求，在肌肉减少症社区，我们建议使用磁共振成像（MRI），以解决 这种需要。 该项目开发了一种临床上可行的工具集，用于无创成像骨骼肌早期萎缩性变化， 肌肉使用磁共振成像（MRI）。我们的具体目标是（1）开发新的MRI技术， 利用新的脉冲序列来量化肌细胞大小及其由于萎缩引起的变化;（2）验证 年轻和老年受试者肌肉活检的MR萎缩成像与组织学评价，以及相关性 （3）应用MRI萎缩方法研究肌肉减少症患者的纵向变化 以及在处于发生肌肉减少症的高风险的虚弱前受试者中。 这项工作的创新在于开发了一种新的成像技术来量化肌肉萎缩 组织非侵入性。该提案的结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。这项工作的意义是一个强大的 临床MRI方案，用于对与肌肉减少症相关的早期退行性变化进行成像， 临床现场。可重复和强大的工具将允许肌肉减少症成像社区识别受试者 风险，并实施有针对性的和及时的干预措施，可以停止或减缓肌肉减少症的进展。

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.