Development and Application of Muscle Diffusion Tensor MRI

项目摘要 我们将推进对人类肌肉结构如何影响功能的定量理解， 健康和疾病;我们将分享磁共振成像（MRI）资源， 与肌肉研究界一起自由地产生这些知识。在生物学的各个层面上 复杂性，肌肉结构显著影响肌肉功能。这些属性包括 被称为肌肉结构的中间尺度关系：肌肉纤维的形状和方向 相对于其机械作用线。我们对肌肉结构如何影响肌肉的理解 然而，这一功能仍然不完善，我们研究这些关系的工具也不充分 开发因此，我们对病理性改变的肌肉是如何在 疾病中的结构，如杜氏肌营养不良症（DMD）， 并加剧了这些肌肉进一步受伤的风险。为了提供这些知识，我们将推动 技术和应用定量MRI技术，如扩散张量成像（DTI），克服 几个剩余的技术挑战和发展的肌肉结构， 功能目的1是验证MRI方法，用于在广泛的运动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纤维跟踪算法， 量化健康，萎缩，发炎和脂肪渗透肌肉的结构，我们将开发和 验证结合联合收割机DTI纤维跟踪和快速采集3D图像来量化肌肉的方法 建筑在收缩。目的2是促进对功能影响的定量理解， 健康和营养不良的人类肌肉的肌肉结构。我们将量化肌肉之间的关系 结构和力的产生、应变的发展以及外周氧供应的充足性。的 这项工作的结果将是一个新确定的生理机制损伤的DMD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 将被免费提供。此外，还将免费提供处理这些数据的软件工具包 并通过合作得到支持。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序列的数据相结合。我们 将创造关于肌肉结构和功能之间关系的新知识， 受到疾病的影响。通过将这些进展发展成一个免费的数据集和工具包，我们将使 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.