In vivo MRI is sensitive to remyelination in a nonhuman primate model of multiple sclerosis.
In vivo MRI is sensitive to remyelination in a nonhuman primate model of multiple sclerosis.
复制标题
DOI：
10.7554/elife.73786
复制
发表时间：
2023-04-21
期刊：
影响因子：
7.7
通讯作者：
Reich DS
中科院分区：
文献类型：
--
作者：
Donadieu M;Lee NJ;Gaitán MI;Ha SK;Luciano NJ;Roy S;Ineichen B;Leibovitch EC;Yen CC;Pham DL;Silva AC;Johnson M;Jacobson S;Sati P;Reich DS
多发性硬化症(MS)的炎性脱髓鞘修复过程中，髓鞘再生起着至关重要的作用。在多发性硬化症中，使用磁共振成像(MRI)研究活体内的再髓鞘形成是困难的，因为收集连续的短间隔扫描是具有挑战性的。利用常见绒猴的实验性自身免疫性脑脊髓炎(EAE)，我们研究了MRI是否对重新髓鞘形成敏感，以及是否可以表征重新髓鞘形成。在6只动物中，根据质子密度加权图像上的信号强度预测为脱髓鞘或重新髓鞘的31个局灶性病变随后进行了组织病理学评估。六只绒猴中有四只发生了重新髓鞘形成，45%的病变发生了重新髓鞘形成。放射病理比较显示，MRI对检测髓鞘再生具有较高的统计学敏感性(100%)和特异性(90%)。这项研究证明了在绒猴EAE中自发再髓鞘形成的盛行率和体内MRI检测它的能力，这对促进再髓鞘形成的药物的临床前测试具有重要意义。
Remyelination is crucial to recover from inflammatory demyelination in multiple sclerosis (MS). Investigating remyelination in vivo using magnetic resonance imaging (MRI) is difficult in MS, where collecting serial short-interval scans is challenging. Using experimental autoimmune encephalomyelitis (EAE) in common marmosets, a model of MS that recapitulates focal cerebral inflammatory demyelinating lesions, we investigated whether MRI is sensitive to, and can characterize, remyelination. In six animals followed with multisequence 7 T MRI, 31 focal lesions, predicted to be demyelinated or remyelinated based on signal intensity on proton density-weighted images, were subsequently assessed with histopathology. Remyelination occurred in four of six marmosets and 45% of lesions. Radiological-pathological comparison showed that MRI had high statistical sensitivity (100%) and specificity (90%) for detecting remyelination. This study demonstrates the prevalence of spontaneous remyelination in marmoset EAE and the ability of in vivo MRI to detect it, with implications for preclinical testing of pro-remyelinating agents.