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

高场肌少症骨骼肌变化的定量和光谱成像

• 批准号: 10877293
• 负责人: Bragi Sveinsson
• 金额: $ 24.9万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10877293
• 关键词: 3-Dimensional; Affect; Age; Agreement; Awareness; Binding; Biological Markers; Clinical; Communities; Consensus; Data; Development; Diffusion; Elderly; Evaluation; Fatty acid glycerol esters; Fiber; Fracture; Frequencies; Future; Gait speed; Geriatrics; Goals; Hand Strength; Health; Health Personnel; Hospitalization; Human; Image; Imaging Techniques; Inflammation; Investigation; Life Expectancy; Lipids; Machine Learning; Magnetic Resonance; Magnetic Resonance Imaging; Measurement; Measures; Medical Imaging; Metabolic; Metabolic Marker; Methods; Morbidity - disease rate; Morphologic artifacts; Morphology; Muscle; Muscle function; Muscular Atrophy; Noise; Patients; Phase; Physiologic pulse; Predisposition; Prevalence; Protons; Proxy; Relaxation; Research; Resolution; Role; Running; Signal Transduction; Site; Skeletal Muscle; Soleus Muscle; Spatial Distribution; Spectrum Analysis; Structure; Techniques; Testing; Time; Tissues; Treatment Effectiveness; United States; Visualization; Water; Work; aging population; bone imaging; carbene; clinical biomarkers; design; diagnostic criteria; falls; imaging biomarker; imaging modality; improved; in vivo; innovation; muscle form; muscle strength; muscular structure; novel; potential biomarker; quantitative imaging; radio frequency; recruit; sarcopenia; spectroscopic imaging; structural imaging; therapy development

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.

项目摘要 肌肉减少症是一种以肌肉质量和老年人功能损失为特征的疾病，正在增加 由于人口老龄化，在美国的相关性。人们普遍认为，肌肉的减弱 在肌肉减少症中，不能仅仅通过肌肉质量的损失来解释，但是背后的机制仍然很差 理解。这部分是由于缺乏观察肌肉结构和 高详细的组成。我们建议开发MRI技术以测量肌肉形态， 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 与肌肉减少症及其与更容易获得的肌肉功能的测量（例如抓地力） 力量和步态速度。这将为正在进行的有关如何这样的辩论提供重要的贡献 测量值可用于定义肌肉减少症，这将为治疗开发铺平道路。 我们旨在开发新的方法，以使用超高场来研究肌肉的结构和组成 MRI。具体而言，我们旨在（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）获取空间分布的图像 骨骼肌中的细胞内脂质，测量甲基和甲基以估计饱和； （3） 通过查看T2的MR测量值进行比较骨骼肌结构和质量的研究 放松率，扩散率（分别是炎症和纤维尺寸的代理），脂肪分数和脂质 组成，在患有肌肉减少症和健康对照的受试者中，看看这些数量与肌肉如何相关 功能。 该项目具有几个创新的方面。首先，我们将开发一种估计肌肉形态的方法，T2 松弛速率和单个MRI序列的扩散率。重要的是，这将成为开发的方法 容易在其他MRI站点运行。其次，我们将设计方法来执行强大，有效的成像 在高场的体内人体骨骼肌中的细胞内脂质液滴分布和饱和。两个 这些方法将具有与图像伪影的无与伦比的信号噪声比和鲁棒性。这 这项工作的重要性是研究炎症，纤维大小和脂质分布在 肌肉减弱的肌肉减弱以及这些测量与肌肉功能如何相关。结果 结论和技术可能有助于建立定义肌肉减少症的共同标准，并有助于帮助 开发这种情况的未来治疗方法。