Early macrophage MRI of inflammatory lesions predicts lesion severity and disease development in relapsing EAE
Early macrophage MRI of inflammatory lesions predicts lesion severity and disease development in relapsing EAE
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DOI：
10.1016/j.neuroimage.2006.03.028
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发表时间：
2006-08-01
期刊：
影响因子：
5.7
通讯作者：
Petry, K. G.
中科院分区：
文献类型：
--
作者：
Brochet, B.;Deloire, M. S. A.;Petry, K. G.
磁共振成像（MRI）在多发性硬化（MS）的诊断和监测中具有重要作用。轴突缺失被认为是累积不可逆残疾的主要原因。利用超小-超-顺磁性-氧化铁（USPIO）纳米颗粒的MRI是一种新技术，用于揭示实验性自身免疫性脑脊髓炎（EAE）中巨噬细胞浸润的体内中枢神经系统（CNS）炎性病变。在这里，我们提出了USPIO增强MRI是否可以作为预测疾病严重程度的工具的问题。我们研究了在具有不同疾病严重程度的复发性EAE模型中，在CNS炎症开始时的个体间差异，如通过MRI与USPIO在体内揭示的，与急性和慢性组织损伤（包括轴突丢失）的严重程度相关。在疾病发作时，观察到USPIO的MRI改变，可将动物分配至USPIO+和USPIO-组。在54.5%的患病大鼠中，首次发作时使用USPIO+的MRI显示主要位于脑干和小脑的信号异常。尽管动物在第一次发作期间没有表现出任何临床显着差异，但与USPIO相比，USPIO+大鼠在第一次发作（发作和启动恢复阶段）时表现出明显更重要的组织变化，在第二次发作时，表现出更严重的临床疾病和轴突丢失。-大鼠。第一次发作时的MRI损伤负荷和体积与炎症、巨噬细胞募集、脱髓鞘、急性轴突损伤以及第二次发作时的轴突损失程度显著相关。这种新的MRI应用在体内监测巨噬细胞浸润提供了一个新的平台，调查炎性脱髓鞘中枢神经系统疾病的严重程度。(c)2006年爱思唯尔公司All rights reserved.
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. (c) 2006 Elsevier Inc. All rights reserved.