Quantification of increased cellularity during inflammatory demyelination
Quantification of increased cellularity during inflammatory demyelination
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DOI：
10.1093/brain/awr307
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发表时间：
2011-12-01
期刊：
影响因子：
14.5
通讯作者：
Song, Sheng-Kwei
中科院分区：
文献类型：
--
作者：
Wang, Yong;Wang, Qing;Song, Sheng-Kwei
多发性硬化症的特点是炎症性脱髓鞘和不可逆的轴索损伤导致永久性神经功能障碍。与标准磁共振成像相比，弥散张量成像在区分轴突和髓鞘病变方面的能力有所提高。然而，扩散张量成像不能检测到炎症相关的细胞增多和血管源性水肿，也不能将其与轴突/髓鞘损伤分离，限制了其临床应用。一种新的扩散基谱成像技术，能够表征与轴突/髓鞘损伤和炎症相关的水扩散特性，用于定量揭示中枢神经系统疾病中的白质病理。采用正常固定小鼠三叉神经并设和不加凝胶的组织模型来证明扩散基谱成像在无血管源性水肿和存在血管源性水肿情况下量化基线细胞量的可行性。在幻体实验的基础上，对铜酮处理小鼠的胼胝体进行体内扩散基谱成像和扩散张量成像，并进行免疫组织化学验证。结果表明，体内扩散基谱成像可以有效分离细胞增多和/或灰质污染的混杂效应，从而成功检测扩散张量成像未检测到的胼胝体中部和吻侧轴突损伤和/或脱髓鞘。此外，扩散基础光谱成像衍生的细胞数量与免疫组织化学测定的细胞核数量密切相关。我们的研究结果表明，扩散基谱成像有很大的潜力为多发性硬化症并发的神经炎症、轴突损伤和脱髓鞘提供无创生物标志物。
Multiple sclerosis is characterized by inflammatory demyelination and irreversible axonal injury leading to permanent neurological disabilities. Diffusion tensor imaging demonstrates an improved capability over standard magnetic resonance imaging to differentiate axon from myelin pathologies. However, the increased cellularity and vasogenic oedema associated with inflammation cannot be detected or separated from axon/myelin injury by diffusion tensor imaging, limiting its clinical applications. A novel diffusion basis spectrum imaging, capable of characterizing water diffusion properties associated with axon/myelin injury and inflammation, was developed to quantitatively reveal white matter pathologies in central nervous system disorders. Tissue phantoms made of normal fixed mouse trigeminal nerves juxtaposed with and without gel were employed to demonstrate the feasibility of diffusion basis spectrum imaging to quantify baseline cellularity in the absence and presence of vasogenic oedema. Following the phantom studies, in vivo diffusion basis spectrum imaging and diffusion tensor imaging with immunohistochemistry validation were performed on the corpus callosum of cuprizone treated mice. Results demonstrate that in vivo diffusion basis spectrum imaging can effectively separate the confounding effects of increased cellularity and/or grey matter contamination, allowing successful detection of immunohistochemistry confirmed axonal injury and/or demyelination in middle and rostral corpus callosum that were missed by diffusion tensor imaging. In addition, diffusion basis spectrum imaging-derived cellularity strongly correlated with numbers of cell nuclei determined using immunohistochemistry. Our findings suggest that diffusion basis spectrum imaging has great potential to provide non-invasive biomarkers for neuroinflammation, axonal injury and demyelination coexisting in multiple sclerosis.