From the Reference Center for Neuromuscular Diseases and ALS (E.F., E.D., S.A.), La Timone University Hospital, Center for Magnetic Resonance in Biology and Medicine (M.A.H., C.M., M.G., D.B.), UMR CNRS 7339, UMR 7286 (E.D.), Medicine Faculty, CNRS, LIS (M.A.H.,M.-E.B.), and Inserm (S.A.), GMGF, Aix-Marseille University, France.
Neurology. 2024 May 14;102(9):e209277. doi: 10.1212/WNL.0000000000209277. Epub 2024 Apr 17.
Intramuscular fat fraction (FF) assessed using quantitative MRI (qMRI) has emerged as one of the few responsive outcome measures in CMT1A suitable for future clinical trials. This study aimed to identify the relevance of multiple qMRI biomarkers for tracking longitudinal changes in CMT1A and to assess correlations between MRI metrics and clinical parameters.
qMRI was performed in CMT1A patients at 2 time points, a year apart, and various metrics were extracted from 3-dimensional volumes of interest at thigh and leg levels. A semiautomated segmentation technique was used, enabling the analysis of central slices and a larger 3D muscle volume. Metrics included proton density (PD), magnetization transfer ratio (MTR), and intramuscular FF. The sciatic and tibial nerves were also assessed. Disease severity was gauged using Charcot Marie Tooth Neurologic Score (CMTNSv2), Charcot Marie Tooth Examination Score, Overall Neuropathy Limitation Scale scores, and Medical Research Council (MRC) muscle strength.
Twenty-four patients were included. FF significantly rose in the 3D volume at both thigh (+1.04% ± 2.19%, = 0.041) and leg (+1.36% ± 1.87%, = 0.045) levels. The 3D analyses unveiled a length-dependent gradient in FF, ranging from 22.61% ± 10.17% to 26.17% ± 10.79% at the leg level. There was noticeable variance in longitudinal changes between muscles: +3.17% ± 6.86% ( = 0.028) in the tibialis anterior compared with 0.37% ± 4.97% ( = 0.893) in the gastrocnemius medialis. MTR across the entire thigh volume showed a significant decline between the 2 time points -2.75 ± 6.58 ( = 0.049), whereas no significant differences were noted for the 3D muscle volume and PD. No longitudinal changes were observed in any nerve metric. Potent correlations were identified between FF and primary clinical measures: CMTNSv2 (ρ = 0.656; = 0.001) and MRC in the lower limbs (ρ = -0.877; < 0.001).
Our results further support that qMRI is a promising tool for following up longitudinal changes in CMT1A patients, FF being the paramount MRI metric for both thigh and leg regions. It is crucial to scrutinize the postimaging data extraction methods considering that annual changes are minimal (around +1.5%). Given the varied FF distribution, the existence of a length-dependent gradient, and the differential fatty involution across muscles, 3D volume analysis appeared more suitable than single slice analysis.
使用定量磁共振成像（qMRI）评估的肌肉内脂肪分数（FF）已成为适合未来临床试验的 CMT1A 中少数几个有反应的结局指标之一。本研究旨在确定多种 qMRI 生物标志物与 CMT1A 纵向变化的相关性，并评估 MRI 指标与临床参数之间的相关性。
在 2 次时间点对 CMT1A 患者进行 qMRI 检查，间隔 1 年，从大腿和小腿 3 维感兴趣区提取各种指标。使用半自动分割技术，可对中央切片和更大的 3D 肌肉体积进行分析。指标包括质子密度（PD）、磁化转移率（MTR）和肌肉内 FF。还评估了坐骨神经和胫神经。使用 Charcot-Marie-Tooth 神经评分（CMTNSv2）、Charcot-Marie-Tooth 检查评分、总体神经受限量表评分和医学研究委员会（MRC）肌肉力量来衡量疾病严重程度。
共纳入 24 例患者。大腿（+1.04%±2.19%，=0.041）和小腿（+1.36%±1.87%，=0.045）3D 体积的 FF 均显著升高。3D 分析揭示了 FF 在小腿水平上的长度依赖性梯度，范围从 22.61%±10.17%到 26.17%±10.79%。不同肌肉之间的纵向变化差异明显：胫骨前肌为+3.17%±6.86%（=0.028），而比目鱼肌内侧为 0.37%±4.97%（=0.893）。整个大腿体积的 MTR 在 2 个时间点之间显示出显著下降-2.75±6.58（=0.049），而 3D 肌肉体积和 PD 则没有显著差异。任何神经指标均未观察到纵向变化。FF 与主要临床指标之间存在很强的相关性：CMTNSv2（ρ=0.656；=0.001）和下肢 MRC（ρ=-0.877；<0.001）。
我们的结果进一步支持 qMRI 是一种有前途的工具，可用于监测 CMT1A 患者的纵向变化，FF 是大腿和小腿区域的主要 MRI 指标。考虑到每年的变化很小（约+1.5%），仔细检查成像后的数据提取方法至关重要。鉴于 FF 的分布不同、存在长度依赖性梯度以及肌肉间的脂肪退化程度不同，3D 体积分析似乎比单切片分析更合适。
