Brochet B, Deloire M S A, Touil T, Anne O, Caillé J M, Dousset V, Petry K G
Université Victor Ségalen Bordeaux 2, EA2966-Neurobiologie des affections de la myéline, BP 78, 146 rue Léo Saignat, 33076 Bordeaux-cedex, France.
Neuroimage. 2006 Aug 1;32(1):266-74. doi: 10.1016/j.neuroimage.2006.03.028. Epub 2006 May 2.
Magnetic resonance imaging (MRI) is of great utility in diagnosis and monitoring of multiple sclerosis (MS). Axonal loss is considered the main cause of accumulating irreversible disability. MRI using ultrasmall-super-paramagnetic-iron-oxide (USPIO) nanoparticles is a new technique to disclose in vivo central nervous system (CNS) inflammatory lesions infiltrated by macrophages in experimental autoimmune encephalomyelitis (EAE). Here, we raised the question of whether USPIO-enhanced MRI could serve as a tool to predict disease severity. We investigated, in a relapsing EAE model with various degrees of disease severity, the interindividual differences at the beginning of CNS inflammation as revealed in vivo by MRI with USPIO in correlation to the severity of both acute and chronic tissue damage including axonal loss. At the onset of the disease, observation of MRI alterations with USPIO allowed assignment of animals into USPIO+ and USPIO- groups. In 54.5% of diseased rats, MRI with USPIO+ at first attack revealed signal abnormalities mainly localized in the brainstem and cerebellum. Although animals did not present any clinically significant differences during the first attack, USPIO+ rats presented significantly more important tissue alterations at the first attack (onset and initiated recovery phase) and, at the second attack, more severe clinical disease with axonal loss compared to USPIO- rats. MRI lesion load and volume at the first attack correlate significantly with inflammation, macrophage recruitment, demyelination, acute axonal damage and, at the second attack, extent of axonal loss. This new MRI application of in vivo monitoring of macrophage infiltration provides a new platform to investigate the severity of inflammatory demyelinating CNS diseases.
磁共振成像（MRI）在多发性硬化症（MS）的诊断和监测中具有重要作用。轴突损失被认为是累积不可逆残疾的主要原因。使用超小型超顺磁性氧化铁（USPIO）纳米颗粒的MRI是一种新技术，可在实验性自身免疫性脑脊髓炎（EAE）中揭示体内被巨噬细胞浸润的中枢神经系统（CNS）炎性病变。在此，我们提出了USPIO增强MRI是否可作为预测疾病严重程度的工具这一问题。我们在具有不同疾病严重程度的复发性EAE模型中进行研究，通过USPIO-MRI在体内揭示中枢神经系统炎症开始时的个体差异，并将其与包括轴突损失在内的急性和慢性组织损伤的严重程度相关联。在疾病发作时，通过USPIO观察MRI改变可将动物分为USPIO+组和USPIO-组。在54.5%的患病大鼠中，首次发作时USPIO+的MRI显示信号异常主要位于脑干和小脑。尽管动物在首次发作期间没有表现出任何临床上的显著差异，但与USPIO-大鼠相比，USPIO+大鼠在首次发作（发作期和开始恢复期）时出现了明显更严重的组织改变，并且在第二次发作时临床疾病更严重且伴有轴突损失。首次发作时MRI病变负荷和体积与炎症、巨噬细胞募集、脱髓鞘、急性轴突损伤显著相关，并且在第二次发作时与轴突损失程度相关。这种用于体内监测巨噬细胞浸润的新MRI应用为研究炎性脱髓鞘性中枢神经系统疾病的严重程度提供了一个新平台。
