Development and Application of Muscle Diffusion Tensor MRI

项目总结 我们将推进对人类肌肉结构如何影响功能的量化理解，在 健康和疾病；我们将分享磁共振成像(MRI)资源 与肌肉研究社区一起自由地生成这些知识。在生物学的各个层面上 复杂性、肌肉结构对肌肉功能有显著影响。这些属性包括 称为肌肉结构的中等尺度关系：肌肉纤维的形状和方向 关于它的机械行动路线。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也不够 发展起来的。因此，在我们对肌肉如何发生病理改变的理解上存在严重的空白 Duchenne肌营养不良症(DMD)等疾病的结构损害体内、整体肌肉功能 并加剧了这些肌肉进一步受伤的风险。为了提供这方面的知识，我们将推进 弥散张量成像(DTI)等定量磁共振成像技术及其应用 仍然存在的几个技术挑战，以及对肌肉结构和 功能。目标1是验证MRI方法在广泛的状态下量化肌肉结构 肌肉健康和疾病，在休息和收缩期间。我们将验证DTI光纤跟踪算法 量化健康的、萎缩的、发炎的和脂肪渗透的肌肉的结构，我们将开发和 验证结合DTI纤维跟踪和快速获取的3D图像来量化肌肉的方法 收缩中的建筑。目标2是促进对功能影响的定量理解 健康和营养不良人类肌肉的肌肉结构。我们将量化肌肉之间的关系 结构和力量的产生，菌株的发展，以及外周供氧的充足。这个 这项工作的成果将是一种新的DMD损伤的生理机制和科学 为使用先进的结构和功能磁共振成像评估和指导治疗奠定了基础。目标3是 分发基于MRI的肌肉结构-功能分析的数据和软件。全身成像数据集 将公之于众。此外，还将免费提供处理这些数据的软件工具包 并通过协作得到支持。总体而言，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是如何 受到疾病的影响。通过将这些改进开发为免费提供的数据集和工具包，我们将实现 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翻译研究。

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.