Abstract：
Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a rare genetic disease with autosomal-dominant inheritance. In this study, we aimed to quantify fatty infiltration (fat fraction [FF]) and magnetization transfer ratio (MTR) in individual muscles of patients with symptomatic and asymptomatic TTR-FAP using magnetic resonance imaging. Secondarily, we aimed to assess correlations with clinical and electrophysiological variables.
A total of 39 patients with a confirmed mutation in the TTR gene (25 symptomatic and 14 asymptomatic) and 14 healthy volunteers were included. A total of 16 muscles were manually delineated in the nondominant lower limb from T1-weighted anatomical images. The corresponding masks were propagated on the MTR and FF maps. Detailed neurological and electrophysiological examinations were conducted in each group.
The MTR was decreased (42.6 AU; p = 0.001) and FF was elevated (14%; p = 0.003) in the lower limbs of the symptomatic group, with preferential posterior and lateral involvement. In the asymptomatic group, elevated FF was quantified in the gastrocnemius lateralis muscle (11%; p = 0.021). FF was significantly correlated with disease duration (r = 0.49, p = 0.015), neuropathy impairment score for the lower limb (r = 0.42, p = 0.041), Overall Neuropathy Limitations Scale score (r = 0.49, p = 0.013), polyneuropathy disability score (r = 0.57, p = 0.03) and the sum of compound muscle action potential (r = 0.52, p = 0.009). MTR was strongly correlated to FF (r = 0.78, p < 0.0001), and a few muscles with an FF within the normal range had a reduced MTR.
These observations suggest that FF and MTR could be interesting biomarkers in TTR-FAP. In asymptomatic patients, FF in the gastrocnemius lateralis muscle could be a good indicator of the transition from an asymptomatic to a symptomatic form of the disease. MTR could be an early biomarker of muscle alterations.
A total of 39 patients with a confirmed mutation in the TTR gene (25 symptomatic and 14 asymptomatic) and 14 healthy volunteers were included. A total of 16 muscles were manually delineated in the nondominant lower limb from T1-weighted anatomical images. The corresponding masks were propagated on the MTR and FF maps. Detailed neurological and electrophysiological examinations were conducted in each group.
The MTR was decreased (42.6 AU; p = 0.001) and FF was elevated (14%; p = 0.003) in the lower limbs of the symptomatic group, with preferential posterior and lateral involvement. In the asymptomatic group, elevated FF was quantified in the gastrocnemius lateralis muscle (11%; p = 0.021). FF was significantly correlated with disease duration (r = 0.49, p = 0.015), neuropathy impairment score for the lower limb (r = 0.42, p = 0.041), Overall Neuropathy Limitations Scale score (r = 0.49, p = 0.013), polyneuropathy disability score (r = 0.57, p = 0.03) and the sum of compound muscle action potential (r = 0.52, p = 0.009). MTR was strongly correlated to FF (r = 0.78, p < 0.0001), and a few muscles with an FF within the normal range had a reduced MTR.
These observations suggest that FF and MTR could be interesting biomarkers in TTR-FAP. In asymptomatic patients, FF in the gastrocnemius lateralis muscle could be a good indicator of the transition from an asymptomatic to a symptomatic form of the disease. MTR could be an early biomarker of muscle alterations.
摘要：
目的：使用磁共振成像（MRI）量化有症状和无症状的甲状腺素运载蛋白家族性淀粉样多发性神经病（TTR-FAP）患者个体肌肉中的脂肪浸润（FF）和磁化转移比（MTR）。其次，我们旨在评估与临床和电生理变量的相关性.
方法：纳入39例TTR基因突变确诊患者（25例有症状，14例无症状）和14例健康志愿者。从T1加权解剖图像中手动描绘了非优势下肢上总共16条肌肉。相应的掩模在MTR和FF图上传播。每组进行详细的神经和电生理检查。
结果：MTR降低（42.6AU，p=0.001)，FF增加(14%，p=0.003）在有症状组的下肢优先受累的后部和外侧。在无症状组中，在腓肠肌外侧肌中量化了FF的增加(11%，p=0.021)。FF与病程显著相关(r=0.49,p=0.015),NIS-LL（r=0.42，p=0.041），ONLS(r=0.49，p=0.013)，PND(r=0.57,p=0.03)和CMAP之和(r=0.52,p=0.009)。MTR与FF密切相关(r=0.78，p<0.0001)，一些FF在正常范围内的肌肉显示MTR降低。
结论：这些观察结果表明，FF和MTR可能是TTR-FAP中有趣的生物标志物。在无症状患者中，腓肠肌外侧肌中的FF可以用作疾病从无症状过渡到有症状形式的良好指标。感兴趣的，MTR可能是肌肉改变的早期生物标志物。
方法：纳入39例TTR基因突变确诊患者（25例有症状，14例无症状）和14例健康志愿者。从T1加权解剖图像中手动描绘了非优势下肢上总共16条肌肉。相应的掩模在MTR和FF图上传播。每组进行详细的神经和电生理检查。
结果：MTR降低（42.6AU，p=0.001)，FF增加(14%，p=0.003）在有症状组的下肢优先受累的后部和外侧。在无症状组中，在腓肠肌外侧肌中量化了FF的增加(11%，p=0.021)。FF与病程显著相关(r=0.49,p=0.015),NIS-LL（r=0.42，p=0.041），ONLS(r=0.49，p=0.013)，PND(r=0.57,p=0.03)和CMAP之和(r=0.52,p=0.009)。MTR与FF密切相关(r=0.78，p<0.0001)，一些FF在正常范围内的肌肉显示MTR降低。
结论：这些观察结果表明，FF和MTR可能是TTR-FAP中有趣的生物标志物。在无症状患者中，腓肠肌外侧肌中的FF可以用作疾病从无症状过渡到有症状形式的良好指标。感兴趣的，MTR可能是肌肉改变的早期生物标志物。
