A quantitative framework to examine sex differences in musculoskeletal scaling and function

摘要 这项提案的目标是开发一个量化框架，将性别作为一个生物变量来处理 肌肉骨骼建模与仿真研究。这一新的框架将使实地了解 肌肉骨骼结构的性别差异如何影响运动生物力学、肌肉骨骼 损伤和神经肌肉疾病。在骨骼解剖、关节力学、 肌肉结构，以及男性和女性之间的运动功能。同样，它也得到了很好的记录 在肌肉骨骼损伤和神经肌肉损伤的易感性方面存在显著的性别差异 疾病。然而，虽然使用计算机模拟运动来研究肌肉骨骼是如何 结构影响神经肌肉损伤和疾病急剧增加，因为在 数值算法和计算能力，所使用的模型是基于肌肉骨骼的 数据(1)来自仅限男性的人口，和/或(2)结合来自男性和 雌性以一种平均的方式排除任何潜在的性别差异。这些深刻的限制使得 没有任何工具来检查肌肉骨骼结构中已知的性别差异如何 影响生物力学、损伤和疾病。 该项目有三个关键目标，将解决这些深刻的限制。第一个目标是 开发一个全面的数字数据库，包括女性和女性的腿部肌肉、关节和骨骼 不同体型的雄性种群。这一目标将通过使用高吞吐量图像来实现 对50例男性和50例女性的磁共振图像进行分割分析。这个 第二个目标将把第一个目标的测量结果合并到一个计算框架中，该框架 支持准确缩放特定性别的下肢模型，包括捕获 以不确定度分析的形式测量变异性。第三个目标将使用第二个目标中的模型 目的开发一种基于模型的分析方法，以产生对低收入人群性别差异的新见解 肢体生物力学。这种分析方法将被用来检验肌肉力量的性别差异。 在行走和着陆过程中。综合起来，这些目标不仅将解决与以下方面有关的关键问题 男性和女性在肌肉骨骼结构和功能上的差异，但也提供了 严格、详细、特定性别的数据和模型数字数据库，将为 整个科学界都在使用。此发布的资源将通过一组工具为现场提供支持 在肌肉骨骼建模研究中，将性别作为生物学变量进行严格检查。

SUMMARY The goal of this proposal is to develop a quantitative framework to address sex as a biological variable in musculoskeletal modeling and simulation research. This new framework will allow the field to understand how sex differences in musculoskeletal structure influence movement biomechanics, musculoskeletal injury, and neuromuscular disease. There are many known differences in bone anatomy, joint mechanics, muscle architecture, and movement function between males and females. Likewise, it is well documented that there are significant sex differences in susceptibility to musculoskeletal injury and neuromuscular disease. However, while the use of computer simulations of movement to study how musculoskeletal structure influences neuromuscular injury and disease has increased dramatically due to advances in numerical algorithms and computational power, the models that are used are based on musculoskeletal data that (1) are derived from a male-only population, and/or (2) combine measures from males and females in a way that averages out any potential sex differences. These profound limitations leave the field without any tools to examine how the known sex differences in musculoskeletal structures may influence biomechanics, injury, and disease. This project has three key aims that will resolve these profound limitations. The first aim will develop a comprehensive digital database of lower limb muscles, joints, and bones across female and male populations of varying body sizes. This aim will be achieved through using high throughput image segmentation analysis of magnetic resonance images collected of 50 male and 50 female subjects. The second aim will incorporate the measurements from the first aim into a computational framework that enables for accurate sex-specific scaling of lower limb models, including the ability to capture the measured variability in the form of uncertainty analysis. The third aim will use the models in the second aim to develop a model-based analysis method to generate novel insights into sex differences in lower limb biomechanics. The analysis method will be applied to examine sex differences in muscle forces during walking and landing. Taken together, these aims will not only address critical questions related to differences in musculoskeletal structure and function between males and females, but also provide a rigorous, detailed, sex-specific digital database of data and models that will be provided open-access for the entire scientific community to use. This posted resource will empower the field with a set of tools to rigorously examine sex as a biological variable in musculoskeletal modeling research.