Myosteatosis is the infiltration of fat in skeletal muscle during the onset of sarcopenia. The quantification of intramuscular adipose tissue (IMAT) can be a feasible imaging modality for the clinical assessment of myosteatosis, important for the early identification of sarcopenia patients and timely intervention decisions. There is currently no standardized method or consensus for such an application. The aim of this study was to develop a method for the detection and analysis of IMAT in clinical HR-pQCT images of the distal tibia to evaluate skeletal muscle during the ageing process, validated with animal and clinical experimentation. A pre-clinical model of ovariectomized (OVX) rats with known intramuscular fat infiltration was used, where gastrocnemii were scanned by micro-computed tomography (micro-CT) at an 8.4 μm isotropic voxel size, and the images were analyzed using our modified IMAT analysis protocol. IMAT, muscle density (MD), and muscle volume (MV) were compared with SHAM controls validated with Oil-red-O (ORO) staining. Furthermore, the segmentation and IMAT evaluation method was applied to 30 human subjects at ages from 18 to 81 (mean = 47.3 ± 19.2). Muscle-related parameters were analyzed with functional outcomes. In the animal model, the micro-CT adipose tissue-related parameter of IMAT% segmented at −600 HU to 100 HU was shown to strongly associate with the ORO-positively stained area (r = 0.898, p = 0.002). For the human subjects, at an adjusted threshold of −600 to −20 HU, moderate positive correlations were found between MV and MD (r = 0.642, p < 0.001), and between MV and IMAT volume (r = 0.618, p < 0.01). Moderate negative correlations were detected between MD and IMAT% (r = −0.640, p < 0.001). Strong and moderate associations were found between age and MD (r = −0.763, p < 0.01), and age and IMAT (r = 0.559, p < 0.01). There was also a strong correlation between IMAT% and chair rise time (r = 0.671, p < 0.01). The proposed HR-pQCT evaluation protocol for intramuscular adipose-tissue produced MD and IMAT results that were associated with age and physical performance measures, and were of good predictive value for the progression of myosteatosis or sarcopenia. The protocol was also validated on animal skeletal muscle samples that showed a good representation of histological lipid content with positive correlations, further supporting the clinical application for the rapid evaluation of muscle quality and objective quantification of skeletal muscle at the peripheral for sarcopenia assessment.

中文翻译：

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HR-pQCT 用于评估衰老骨骼肌的肌肉质量和肌内脂肪浸润

肌肉脂肪变性是肌肉减少症发作期间骨骼肌中脂肪的浸润。肌内脂肪组织 (IMAT) 的量化可以成为肌肉脂肪变性临床评估的一种可行的成像方式，对于肌肉减少症患者的早期识别和及时的干预决策非常重要。目前还没有针对此类应用程序的标准化方法或共识。本研究的目的是开发一种检测和分析胫骨远端临床 HR-pQCT 图像中 IMAT 的方法，以评估衰老过程中的骨骼肌，并通过动物和临床实验进行验证。使用具有已知肌内脂肪浸润的卵巢切除 (OVX) 大鼠的临床前模型，其中通过微型计算机断层扫描 (micro-CT) 以 8.4 μm 各向同性体素大小扫描腓肠肌，并使用我们修改后的 IMAT 分析协议对图像进行了分析。将 IMAT、肌肉密度 (MD) 和肌肉体积 (MV) 与使用油红 O (ORO) 染色验证的 SHAM 对照进行比较。此外，将分割和 IMAT 评估方法应用于 30 名年龄在 18 至 81 岁之间的人类受试者（平均值 = 47.3 ± 19.2）。肌肉相关参数与功能结果进行了分析。在动物模型中，显微 CT 脂肪组织相关参数 IMAT% 在 -600 HU 至 100 HU 处分段显示与 ORO 阳性染色区域密切相关（r = 0.898，将分割和 IMAT 评估方法应用于 30 名年龄在 18 至 81 岁之间的人类受试者（平均 = 47.3 ± 19.2）。肌肉相关参数与功能结果进行了分析。在动物模型中，显微 CT 脂肪组织相关参数 IMAT% 在 -600 HU 至 100 HU 处分段显示与 ORO 阳性染色区域密切相关（r = 0.898，将分割和 IMAT 评估方法应用于 30 名年龄在 18 至 81 岁之间的人类受试者（平均 = 47.3 ± 19.2）。肌肉相关参数与功能结果进行了分析。在动物模型中，显微 CT 脂肪组织相关参数 IMAT% 在 -600 HU 至 100 HU 处分段显示与 ORO 阳性染色区域密切相关（r = 0.898，p = 0.002）。对于人类受试者，在 -600 至 -20 HU 的调整阈值下，在 MV 和 MD 之间（r = 0.642， p < 0.001）以及 MV 和 IMAT 体积之间（r = 0.618，p < 0.01 ）发现了适度的正相关). 在 MD 和 IMAT% 之间检测到中度负相关（r = −0.640，p < 0.001）。在年龄和 MD (r = −0.763, p < 0.01) 以及年龄和 IMAT (r = 0.559, p < 0.01)之间发现了强和中度关联。IMAT% 和椅子上升时间之间也有很强的相关性 (r = 0.671, p< 0.01)。拟议的肌内脂肪组织 HR-pQCT 评估方案产生的 MD 和 IMAT 结果与年龄和身体性能测量相关，并且对肌肉脂肪变性或肌肉减少症的进展具有良好的预测价值。该协议还在动物骨骼肌样本上进行了验证，这些样本显示了具有正相关性的组织学脂质含量的良好表现，进一步支持了快速评估肌肉质量和客观量化外周肌肉减少症评估骨骼肌的临床应用。