McCrady Allison, Friedman Seth, Wang Leo, Shaw Dennis, Tawil Rabi, Statland Jeffery, Tapscott Stephen, Blemker Silvia
Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia, United States of America.
Center for Respiratory Biology and Therapeutics, Seattle Children's, Seattle, Washington, United States of America.
PLoS One. 2025 Jul 18;20(7):e0319881. doi: 10.1371/journal.pone.0319881. eCollection 2025.
Facioscapulohumeral muscular dystrophy (FSHD) is a progressive neuromuscular disorder characterized by muscle damage, fibro-fatty infiltration, and ultimately weakness. The tibialis anterior (TA), very often involved relatively early in FSHD, is a primary dorsiflexor and important for ambulation. Recent work using magnetic resonance imaging to quantify fat infiltration in the TA volume observed a steep decline in force generation after fat reached ~20% in volume. Additional imaging studies have identified regional fat infiltration patterns that may contribute to the non-linear relationship between fat volume and muscle strength due to the distribution of fat within the muscle structure. The goals of this study were to 1) develop a pipeline for creating subject-specific models of the TA that include fat infiltration patterns measured from MRI and predict force generation, 2) compare models created using this pipeline with clinical measures of muscle strength, and 3) use the models to investigate the impact of regional fat distribution on muscle force generation. Twelve subject-specific models were created, and the model-predicted forces strongly correlate to clinical measures of strength in the same subjects (manual muscle testing (MMT): r = 0.75, and quantitative muscle testing (QMT): r = 0.54). The models showed fat amount accounts for 48% and muscle volume accounts for 74% of the variation in force. To investigate the impact of fat distribution, we developed eight pseudo maps to systematically vary fat location and amount in all subject-specific geometries. The models revealed that fat location modulates force generation, with the middle region involvement having the greatest impact in reducing force. This work highlights the need to characterize and understand the impact of intra-muscular fat distributions in neuromuscular diseases.
面肩肱型肌营养不良症（FSHD）是一种进行性神经肌肉疾病，其特征为肌肉损伤、纤维脂肪浸润，最终导致肌无力。胫前肌（TA）在FSHD中常常相对较早受累，它是主要的背屈肌，对行走很重要。最近利用磁共振成像对TA体积内的脂肪浸润进行量化的研究发现，当脂肪体积达到约20%后，力量产生会急剧下降。其他影像学研究已经确定了区域脂肪浸润模式，由于脂肪在肌肉结构内的分布，这些模式可能导致脂肪体积与肌肉力量之间呈非线性关系。本研究的目的是：1）开发一种流程，用于创建包含从MRI测量得到的脂肪浸润模式并预测力量产生的TA个体特异性模型；2）将使用该流程创建的模型与肌肉力量的临床测量结果进行比较；3）使用这些模型研究区域脂肪分布对肌肉力量产生的影响。创建了12个个体特异性模型，模型预测的力量与同一受试者的力量临床测量结果高度相关（徒手肌力测试（MMT）：r = 0.75，定量肌肉测试（QMT）：r = 0.54）。模型显示，力量变化中48%由脂肪量引起，74%由肌肉体积引起。为了研究脂肪分布的影响，我们开发了八个伪地图，以系统地改变所有个体特异性几何结构中的脂肪位置和数量。模型显示，脂肪位置会调节力量产生，中部区域受累对力量降低的影响最大。这项工作强调了在神经肌肉疾病中描述和理解肌肉内脂肪分布影响的必要性。
