Translational Neuroradiology Section, Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States.
Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, United States.
Elife. 2023 Apr 21;12:e73786. doi: 10.7554/eLife.73786.
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.
髓鞘再生对于多发性硬化症(MS)的炎症性脱髓鞘病变的恢复至关重要。在多发性硬化症中,使用磁共振成像(MRI)进行体内髓鞘再生研究具有挑战性,因为很难连续采集短间隔扫描。本研究使用常见绒猴的实验性自身免疫性脑脊髓炎(EAE)作为多发性硬化症的模型,该模型可重现局灶性脑炎症性脱髓鞘病变,我们研究了 MRI 是否能敏感地检测和表征髓鞘再生。在对 6 只动物进行多序列 7T MRI 随访的过程中,根据质子密度加权图像上的信号强度预测 31 个局灶性病变为脱髓鞘或髓鞘再生,随后进行了组织病理学评估。6 只绒猴中有 4 只发生了髓鞘再生,占 45%的病变。放射病理学比较表明,MRI 对检测髓鞘再生具有很高的统计学敏感性(100%)和特异性(90%)。这项研究证明了在绒猴 EAE 中自发髓鞘再生的普遍性,以及体内 MRI 检测髓鞘再生的能力,这对研究促进髓鞘再生的药物具有重要意义。