In vivo MRI of spinal cord lesions in EAE mice

描述(申请人提供)：脑白质和脊髓中的脱髓鞘病变是自身免疫性疾病多发性硬化症(MS)的病理标志。活动性病变，如Gd增强T1加权MRI所观察到的，在组织学检查中显示不同程度的炎症、脱髓鞘和轴突损伤。拟议研究的目的是确定炎症、脱髓鞘和轴突损伤的时间进程及其对病变形成和进展的贡献。对实验性自身免疫性脑脊髓炎(EAE)小鼠的脊髓进行了纵向的活体研究，EAE是MS的一个模型，将使用MRI进行检查。将分别使用磁性负载T细胞和Gd增强来评估血脑屏障的炎症和破坏(目标1)。将使用扩散张量成像评估脱髓鞘和轴突损伤的程度(目标2)。所有活体MRI结果将与神经功能障碍相关，并通过体外MRI和组织学分析进行验证。这项研究将加强对EAE和MS的动态病理变化的了解，并将评估DTI作为诊断工具的使用。

DESCRIPTION (provided by applicant): Demyelinated lesions in the white matter of the brain and spinal cord are the pathological hallmark of the autoimmune disorder Multiple Sclerosis (MS). Active lesions, as observed in gadolinium (Gd) enhanced T1- weighted MRI, exhibit varying degrees of inflammation, demyelination, and axonal damage upon histological examination. The objective of the proposed study is to determine the time-course of inflammation, demyelination, and axonal damage and their contribution to lesion formation and progression. A longitudinal, in vivo investigation of the spinal cord in mice with experimental autoimmune encephalomyelitis (EAE), a model of MS, will be examined using MRI. Inflammation and breakdown of the blood-brain barrier will be assessed using magnetically loaded T-cells and Gd-enhancement, respectively (Aim 1). The extent of demyelination and axonal damage will be assessed using diffusion tensor imaging (Aim 2). All in vivo MRI findings will be correlated with neurological disability and validated with ex vivo MRI and histological analysis. The research will enhance the understanding of the dynamic pathological changes in EAE and MS and will assess the use of DTI as a diagnostic tool.