Quantitative and Spectroscopic Imaging of Skeletal Muscle Changes in Sarcopenia at High Field

项目摘要 肌肉减少症是一种以老年人肌肉质量和功能丧失为特征的疾病， 在美国，由于其人口老龄化。人们普遍认为，肌肉的弱化 在肌肉减少症中，不能仅仅用肌肉质量的损失来解释，但这背后的机制仍然很差。 明白这部分是由于缺乏观察肌肉结构的非侵入性技术， 高细节的组成。我们建议开发MRI技术来测量肌肉形态， 微观结构和脂肪含量，以详细了解患者肌肉数量和质量的变化 肌肉减少症以及它们如何与更容易获得的肌肉功能测量（例如握力）相关 力量和步态速度。这将为正在进行的关于如何使这种做法 测量结果可用于定义肌肉减少症，这将为治疗开发铺平道路。 我们的目标是开发新的方法来研究肌肉的结构和组成，使用超高场 核磁共振具体来说，我们的目标是（1）获得骨骼肌宏观和微观结构的水基图像， 无与伦比的效率，图像质量和分辨率;（2）获得空间分布的图像 骨骼肌中的肌细胞内脂质，测量甲基和亚甲基以估计饱和度;以及（3） 进行一项研究，通过观察T2的MR测量值， 松弛率、扩散率（分别作为炎症和纤维尺寸的代表）、脂肪分数和脂质 在患有肌肉减少症的受试者和健康对照者中，观察这些量与肌肉的相关性。 功能 这个项目有几个创新的方面。首先，我们将开发一种方法来估计肌肉形态， 弛豫率和扩散率与一个单一的MRI序列。重要的是，这将使开发的方法 易于在其他MRI站点运行。其次，我们将设计方法来执行强大的，有效的成像， 高场强下人体骨骼肌细胞内脂滴分布和饱和度两 这些方法将具有无与伦比的信噪比和对图像伪像的鲁棒性。的 这项工作的意义在于研究炎症，纤维大小和脂质分布在炎症中的作用。 肌肉减少症中的肌肉弱化以及这些测量如何与肌肉功能相关。所得 结论和技术可以帮助建立用于定义肌肉减少症的共同标准， 这种疾病未来治疗的发展。

Project Summary Sarcopenia, a condition characterized by loss of muscle mass and function in the elderly, is of increasing relevance in the United States due to its aging population. It is generally agreed that the weakening of the muscle in sarcopenia cannot be explained by loss of muscle mass alone, but the mechanisms behind this remain poorly understood. This is partly due to the lack of non-invasive techniques for observing muscle structure and composition in high detail. We propose to develop MRI techniques to measure muscle morphology, microstructure, and fat content to get a detailed view of the changes in muscle quantity and quality in patients with sarcopenia and how they relate to more easily attainable measurements of muscle function such as grip strength and gait speed. This would provide an important contribution to the ongoing debate about how such measurements could be used to define sarcopenia, which would pave the way for treatment development. We aim to develop novel methods to investigate the structure and composition of muscle using ultra-high-field MRI. Specifically, we aim to (1) obtain water-based images of skeletal muscle macro- and microstructure with unparalleled efficiency, image quality, and resolution; (2) obtain images of the spatial distribution of intramyocellular lipids in skeletal muscle, measuring both methyl and methylene to estimate saturation; and (3) to conduct a study comparing skeletal muscle structure and quality by looking at MR measurements of T2 relaxation rates, diffusivity (as proxies for inflammation and fiber size, respectively), fat fraction, and lipid composition, in subjects with sarcopenia and healthy controls and see how these quantities correlate to muscle function. This project has several innovative aspects. First, we will develop a method to estimate muscle morphology, T2 relaxation rates, and diffusivity with a single MRI sequence. Importantly, this will make the developed method easy to run at other MRI sites. Second, we will devise methods to perform robust, efficient imaging of intramyocellular lipid droplet distribution and saturation in human skeletal muscle in vivo at high field. Both of these methods will have unparalleled signal-to-noise ratio and robustness against image artifacts. The significance of this work is the investigation of the role of inflammation, fiber size, and lipid distribution in the weakening of muscle in sarcopenia and how these measurements are related to muscle function. The resulting conclusions and techniques may help establish a common standard for the definition of sarcopenia and aid in the development of future treatments for this condition.