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

总结 该提案的目标是制定一个量化框架，将性别作为一个生物变量， 肌肉骨骼建模与仿真研究。这一新框架将使该领域能够理解 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。在骨骼解剖学、关节力学、 肌肉结构和运动功能的差异。同样， 在对肌肉骨骼损伤和神经肌肉损伤的易感性方面存在显着的性别差异， 疾病然而，虽然使用计算机模拟运动来研究肌肉骨骼如何 结构影响神经肌肉损伤和疾病急剧增加，由于进展， 数值算法和计算能力，所使用的模型是基于肌肉骨骼 数据（1）仅来自男性人群，和/或（2）联合收割机测量男性和 以平衡任何潜在的性别差异。这些深刻的局限性使 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可能 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。第一个目标将 开发一个全面的数字数据库，包括女性下肢肌肉、关节和骨骼， 不同体型的雄性种群。这一目标将通过使用高通量图像来实现 对50名男性和50名女性受试者的磁共振图像进行分割分析。的 第二个目标将把第一个目标的测量结果纳入一个计算框架， 能够准确地对下肢模型进行性别特异性缩放，包括能够捕获 以不确定性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 旨在开发一种基于模型的分析方法，以产生新的见解，性别差异，在较低的 肢体生物力学分析方法将被应用于检查肌肉力量的性别差异 在行走和着陆时。总的来说，这些目标不仅将解决与以下方面有关的关键问题： 男性和女性之间肌肉骨骼结构和功能的差异，但也提供了一个 严格、详细、针对性别的数据和模型数字数据库， 供整个科学界使用。这个发布的资源将使该领域拥有一套工具， 严格检查性别作为肌肉骨骼建模研究中的生物变量。

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.