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

项目摘要/摘要 骨质疏松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。虽然新的治疗方法已经显示出希望 在改善功能结果方面，它们一直受到缺乏对 疾病的早期阶段。特别是，对肌肉萎缩的非侵入性评估是一项长期公认的 石棺减少社区中未得到满足的需求，我们建议使用磁共振成像(MRI)来解决 这种需要。 该项目开发了一种临床上可行的工具集，以非侵入性方式成像骨骼早期萎缩变化 使用核磁共振成像(MRI)检查肌肉。我们的具体目标是(1)开发新的核磁共振技术， 利用一种新的脉冲序列来量化肌肉细胞的大小及其因萎缩而发生的变化；(2)验证 MR萎缩成像与青年和老年受试者肌肉活检的组织学评估之间的相关性 (3)应用MRI萎缩方法研究肌萎缩症患者的纵向变化 而在身体虚弱的受试者中，这些受试者患石棺减少的风险很高。 这项工作的创新之处在于开发了一种新的成像技术来量化肌肉萎缩 非侵入性的组织。这一提议的结果是一种经过验证的定量MRI工具来对肌肉进行成像 质量，以及它与患者力量和功能状态的关系。这项工作的意义是强大的 临床MRI方案，以成像与骨骼减少相关的早期退行性变化，可转移到任何 临床站点。这个可重现且功能强大的工具将允许石棺减少症成像社区在 风险，并实施针对性和及时的干预措施，以阻止或减缓石棺减少的进展。

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.