Development and Application of Muscle Diffusion Tensor MRI

项目概要 我们将推进对人体肌肉结构如何影响功能的定量理解， 健康与疾病；我们将分享用于核磁共振成像 (MRI) 的资源 与肌肉研究社区自由地生成这些知识。在生物的各个层面 复杂性，肌肉结构显着影响肌肉功能。这些属性包括 称为肌肉结构的中间尺度关系：肌肉纤维的形状和方向 就其机械作用线而言。我们对肌肉结构如何影响肌肉的理解 然而，功能仍然不完整，我们研究这些关系的工具还不够充分 开发的。因此，我们对肌肉如何病理改变的理解存在严重差距。 杜氏肌营养不良症 (DMD) 等疾病中的结构会损害体内整体肌肉功能 并加剧这些肌肉进一步受伤的风险。为了提供这些知识，我们将推进 扩散张量成像（DTI）等定量 MRI 技术和应用，克服 剩下的几个技术挑战以及加深对肌肉结构和 功能。目标 1 是验证 MRI 方法，用于量化各种状态下的肌肉结构 休息和收缩时的肌肉健康和疾病。我们将验证 DTI 光纤跟踪算法 量化健康、萎缩、发炎和脂肪浸润肌肉的结构，我们将开发和 验证结合 DTI 纤维跟踪和快速采集的 3D 图像来量化肌肉的方法 收缩期间的建筑。目标 2 是促进对功能影响的定量理解 健康和营养不良的人体肌肉的肌肉结构。我们将量化肌肉之间的关系 结构和力的产生、应变的发展以及周围氧气供应的充足性。的 这项工作的成果将是新确定的 DMD 损伤的生理机制和科学依据 使用先进的结构和功能 MR 成像来评估和指导治疗奠定了基础。目标 3 是 分发用于基于 MRI 的肌肉结构功能分析的数据和软件。全身成像数据集 将向公众公布。此外，用于处理这些数据的软件工具包将免费提供 并通过合作提供支持。总的来说，我们将开发分析 DTI 数据的最佳方法 健康和患病的肌肉，并将这些数据与其他 MRI 序列提供的数据相结合。我们 将创造关于肌肉结构和功能之间的关系以及它们如何存在的新知识 受疾病影响。通过将这些进步开发成可免费使用的数据集和工具包，我们将能够 世界各地的肌肉骨骼研究人员将这些方法应用于应用生理学和转化研究。

PROJECT SUMMARY We will advance the quantitative understanding of how human muscle structure impacts function, in health and disease; and we will share the magnetic resonance imaging (MRI) resources used to generate this knowledge freely with the muscle research community. At every level of biological complexity, muscle structure significantly influences muscle function. These properties include the intermediate-scale relationships known as muscle architecture: the shape and orientation of a muscle’s fibers with respect to its mechanical line of action. Our understanding of how muscle architecture affects muscle function remains incomplete, however, and our tools for studying these relationships are insufficiently developed. As a result, there are critical gaps in our understanding of how pathologically altered muscle architecture in diseases such as Duchenne muscular dystrophy (DMD) impairs in vivo, whole-muscle function and exacerbates these muscles’ risk of further injury. To provide this knowledge, we will advance the technology and application of quantitative MRI techniques such as diffusion-tensor imaging (DTI), overcoming several remaining technical challenges and developing an improved understanding of muscle architecture and function. Aim 1 is to validate MRI methods for quantifying muscle architecture in a broad range of states of muscle health and disease, at rest and during contraction. We will validate DTI fiber-tracking algorithms for quantifying the architecture of healthy, atrophied, inflamed, and fat-infiltrated muscles, and we will develop and validate methods that combine DTI fiber-tracking and rapidly acquired 3D images to quantify muscle architecture during contraction. Aim 2 is to advance the quantitative understanding of the functional impact of muscle architecture in healthy and dystrophic human muscle. We will quantify the relationships among muscle architecture and force generation, strain development, and the sufficiency of peripheral oxygen supply. The outcome of this work will be a newly identified physiologic mechanism of injury in DMD and the scientific foundation for using advanced structural and functional MR imaging to evaluate and guide therapy. Aim 3 is distribute data and software for MRI-based muscle structure-function analysis. A whole-body imaging dataset will be made publically available. Also, a software toolkit for processing these data will be made freely available and supported through collaborations. Overall, we will develop optimal methods for analyzing DTI data from healthy and diseased muscles and integrating these data with those available from other MRI sequences. We will create new knowledge about the relationships between muscle structure and function and how they are impacted by disease. By developing these advances into a freely available dataset and toolkit, we will enable musculoskeletal researchers worldwide to apply these methods in applied physiology and translational studies.