PDF(Pubmed)
Abstract：
Myelin repair is an unrealized therapeutic goal in the treatment of multiple sclerosis (MS). Uncertainty remains about the optimal techniques for assessing therapeutic efficacy and imaging biomarkers are required to measure and corroborate myelin restoration. We analyzed myelin water fraction imaging from ReBUILD, a double-blind, randomized placebo-controlled (delayed treatment) remyelination trial, that showed a significant reduction in VEP latency in patients with MS. We focused on brain regions rich in myelin. Fifty MS subjects in two arms underwent 3T MRI at baseline and months 3 and 5. Half of the cohort was randomly assigned to receive treatment from baseline through 3 mo, whereas the other half received treatment from 3 mo to 5 mo post-baseline. We computed myelin water fraction changes occurring in normal-appearing white matter of corpus callosum, optic radiations, and corticospinal tracts. An increase in myelin water fraction was documented in the normal-appearing white matter of the corpus callosum, in correspondence with the administration of the remyelinating treatment clemastine. This study provides direct, biologically validated imaging-based evidence of medically induced myelin repair. Moreover, our work strongly suggests that significant myelin repair occurs outside of lesions. We therefore propose myelin water fraction within the normal-appearing white matter of the corpus callosum as a biomarker for clinical trials looking at remyelination.
摘要：
髓磷脂修复是多发性硬化症（MS）治疗中未实现的治疗目标。关于评估治疗效果的最佳技术的不确定性仍然存在，并且需要成像生物标志物来测量和证实髓鞘恢复。我们分析了来自ReBUILD的髓鞘水部分成像，双盲，随机安慰剂对照（延迟治疗）髓鞘再生试验，这表明MS患者的VEP潜伏期显着减少。我们专注于富含髓鞘的大脑区域。两组中的50名MS受试者在基线和第3个月和第5个月接受了3TMRI。一半的队列被随机分配到接受治疗从基线到3个月，而另一半在基线后3个月至5个月接受治疗.我们计算了出现在正常出现的call体白质中的髓鞘水分数变化，光辐射,和皮质脊髓束。在正常出现的call体白质中，髓鞘水含量增加，与再髓鞘治疗氯马斯汀的给药相对应。这项研究提供了直接的，医学诱导髓鞘修复的生物学验证的影像学证据。此外，我们的工作有力地表明,显著的髓鞘修复发生在损伤之外.因此，我们建议正常出现的call体白质中的髓磷脂水部分作为寻找髓鞘再生的临床试验的生物标志物。
