MRI-based computer models of DMD gait to explain selective muscle degeneration

 描述（由申请人提供）：杜氏肌营养不良症（DMD）是一种肌营养不良蛋白基因的遗传突变，每3500名男性新生儿中有1例受影响，导致快速进行性肌肉变性。患有DMD的男孩通常在十几岁时逐渐失去肌肉，并在二三十岁时死于呼吸和心脏并发症。目前，DMD还没有确切有效的治疗方法。虽然潜在的治疗方法仍处于试验阶段，但DMD患者的护理和运动管理的优先事项是延长寿命，维持生活质量和延长寿命。然而，目前缺乏科学的指导方针，为DMD男孩制定安全的运动管理。更好地了解身体活动如何导致DMD的肌肉退化，对于建立尽可能长时间保持amphibia的循证实践至关重要。目前尚不清楚为什么DMD（选择性变性）中某些下肢肌肉比其他肌肉退化得更快，尽管所有下肢肌肉都缺乏肌营养不良蛋白。虽然多种因素可能影响退化的速度，但我们的中心假设是， 对于DMD患者的下肢肌肉，行走时不同程度的离心收缩对选择性退变有重要作用。我们工作的目标是开发计算机模型来预测各种活动对DMD肌肉退化进展的影响，从而为DMD护理和运动管理提供科学指导。由于步行是下肢肌肉最频繁和最重要的活动，因此该探索性项目将测试以下假设：从步行的肌肉骨骼模拟中估计的离心收缩预测DMD儿童下肢肌肉退化的模式。这项工作将为确定运动和设计辅助设备提供更科学的依据，这些设备可以促进肌肉健康和流动性，同时最大限度地减少DMD儿童的损伤。我们建议整合计算机模拟，步态实验和磁共振成像（MRI），以实现这一目标有两个具体的目标。在目标1中，我们将确定步态过程中的肌肉负荷-从计算机模拟中确定-预测DMD中下肢肌肉的选择性退化。在目标2中，我们将确定DMD步态受损是否会导致步态期间肌肉负荷增加。该项目将提供一个新的创新框架，用于开发优化步态和延长步行时间的康复方案。在这个项目中开发的实验模拟框架可以进一步应用于了解各种其他活动对DMD进展的影响，并可能对其他类型的肌营养不良症的进展，如贝克尔或肢带。这里提出的研究将是至关重要的，以制定护理和运动管理的定量指南，以及在设计辅助设备，将减轻肌肉退化，延长american，保持生活质量和提高寿命。

 DESCRIPTION (provided by applicant): Duchenne muscular dystrophy (DMD), a genetic mutation in the dystrophin gene that affects 1 in 3500 male births, causes rapid progressive muscle degeneration. Boys with DMD gradually lose ambulation, often in their teens, and die of respiratory and cardiac complications by their twenties or thirties. Currently, there are no definitive effective cures for DMD. While potential treatments are in trial phases, priorities of care and exercise management for patients with DMD are to prolong ambulation, maintain quality of life and improve longevity. However, there is currently a paucity of scientifically base guidelines for prescribing safe exercise management for boys with DMD. A better understanding of how physical activity leads to muscle degeneration in DMD is critical for establishing evidence-based practices for maintaining ambulation as long as possible. It remains unclear why some lower limb muscles degenerate more quickly than others in DMD (selective degeneration), despite the fact that dystrophin is deficient in all lower limb muscles. Although multiple factors could affect the pace of degeneration, our central hypothesis is that specifically for lower limb muscles in DMD, differing degree of eccentric contraction during walking across muscles significantly contributes to the selective degeneration. The goal of our work is to develop computer models to predict the impact of various activities on the progression of muscle degeneration in DMD, thereby providing scientific guidelines for DMD care and exercise management. Since walking is the most frequent and essential activity for lower limb muscles, this exploratory project will test the hypothesis that eccentric contractions estimated from musculoskeletal simulations of walking predict the patterns of muscle degeneration in the lower limb of children with DMD. This work will lead to a more scientific basis for determining exercise and designing assistive devices that promote muscle health and mobility while minimizing damage in children with DMD. We propose to integrate computer simulations, gait experiments and magnetic resonance imaging (MRI) to achieve this goal with two specific aims. In aim 1, we will determine if muscle loads during gait - determined from computer simulations - predict selective degeneration of lower limb muscles in DMD. In aim 2, we will determine if impaired DMD gait leads to increased muscle loads during gait. This project will provide a new innovative framework for developing rehabilitation regimens that optimize gait and prolong ambulation. The experiment-simulation framework developed in this project can be further applied to understand the influences of various other activities on the progression of DMD, and potentially on the progression of other types of muscular dystrophy, such as Becker or Limb-Girdle. The research proposed here will be crucial to develop quantitative guidelines for care and exercise management as well as in designing assistive devices that would alleviate muscle degeneration, prolonging ambulation, maintaining quality of life and improving longevity.