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Ex vivo MR Microscopy of a Human Brain with Multiple Sclerosis: Visualizing Individual Cells in Tissue Using Intrinsic Iron
NeuroImage ( IF 4.7 ) Pub Date : 2020-12-01 , DOI: 10.1016/j.neuroimage.2020.117285
Govind Nair 1 , Stephen Dodd 2 , Seung-Kwon Ha 3 , Alan P Koretsky 2 , Daniel S Reich 3
Affiliation  

Purpose: To perform magnetic resonance microscopy (MRM) on human cortex and a cortical lesion as well as the adjacent normal appearing white matter. To shed light on the origins of MRI contrast by comparison with histochemical and immunostaining. Methods: 3D MRM at a nominal isotropic resolution of 15 and 18 μm was performed on 2 blocks of tissue from the brain of a 77-year-old man who had MS for 47 years. One block contained normal appearing cortical gray matter (CN block) and adjacent normal appearing white matter (NAWM), and the other also included a cortical lesion (CL block). Postmortem ex-vivo MRI was performed at 11.7T using a custom solenoid coil and T2*-weighted 3D GRE sequence. Histochemical and immunostaining were done after paraffin embedding for iron, myelin, oligodendrocytes, neurons, blood vessels, macrophages and microglia, and astrocytes. Results: MRM could identify individual iron-laden oligodendrocytes with high sensitivity (70% decrease in signal compared to surrounding) in CN and CL blocks, as well as some iron-laden activated macrophages and microglia. Iron-deficient oligodendrocytes seemed to cause relative increase in MRI signal within the cortical lesion. High concentration of myelin in the white matter was primarily responsible for its hypointense appearance relative to the cortex, however, signal variations within NAWM could be attributed to changes in density of iron-laden oligodendrocytes. Conclusion: Changes in iron accumulation within cells gave rise to imaging contrast seen between cortical lesions and normal cortex, as well as the patchy signal in NAWM. Densely packed myelin and collagen deposition also contributed to MRM signal changes. Even though we studied only one block each from normal appearing and cortical lesions, such studies can help better understand the origins of histopathological and microstructural correlates of MRI signal changes in multiple sclerosis and contextualize the interpretation of lower-resolution in vivo MRI scans.

中文翻译:

患有多发性硬化症的人脑的离体 MR 显微镜检查:使用内在铁对组织中的单个细胞进行可视化

目的:对人体皮层和皮层病变以及相邻的正常出现的白质进行磁共振显微镜检查(MRM)。通过与组织化学和免疫染色进行比较,阐明 MRI 造影剂的起源。方法:对来自患有 MS 47 年的 77 岁男性大脑的 2 块组织进行标称各向同性分辨率为 15 和 18 μm 的 3D MRM。一个块包含正常出现的皮质灰质(CN块)和相邻的正常出现的白质(NAWM),另一个还包括一个皮质病变(CL块)。使用定制螺线管线圈和 T2* 加权 3D GRE 序列以 11.7T 进行死后离体 MRI。石蜡包埋后对铁、髓鞘、少突胶质细胞、神经元、血管、巨噬细胞和小胶质细胞进行组织化学和免疫染色,和星形胶质细胞。结果:MRM 可以在 CN 和 CL 块中以高灵敏度(与周围环境相比信号降低 70%)识别单个负载铁的少突胶质细胞,以及一些负载铁的活化巨噬细胞和小胶质细胞。缺铁少突胶质细胞似乎导致皮质病变内 MRI 信号的相对增加。白质中高浓度的髓鞘是其相对于皮层的低信号外观的主要原因,然而,NAWM 内的信号变化可归因于含铁少突胶质细胞密度的变化。结论:细胞内铁积累的变化引起了皮质病变和正常皮质之间的成像对比度,以及 NAWM 中的斑片信号。密集的髓鞘和胶原沉积也有助于 MRM 信号的变化。
更新日期:2020-12-01
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