Hou Jin, Wang Wei, Quan Xianyue, Liang Wen, Li Zhiming, Chen Deji, Han Hongbin
Department of Radiology, The 2nd Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China (mainland).
Department of Radiology and Peking Magnetic Resonance Imaging Technology Research Laboratory, 3rd Hospital of Peking University, Beijing, China (mainland).
Med Sci Monit. 2017 Sep 3;23:4260-4268. doi: 10.12659/msm.903010.
BACKGROUND This study assessed an innovative tracer-based magnetic resonance imaging (MRI) system to visualize the dynamic transportation of tracers in regions of deep brain extracellular space (ECS) and to measure transportation ability and ECS structure. MATERIAL AND METHODS Gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) was the chosen tracer and was injected into the caudate nucleus and thalamus. Real-time dynamic transportation of Gd-DTPA in ECS was observed and the results were verified by laser scanning confocal microscopy. Using Transwell assay across the blood-brain barrier, a modified diffusion equation was further simplified. Effective diffusion coefficient D* and tortuosity λ were calculated. Immunohistochemical staining and Western blot analysis were used to investigate the extracellular matrix contributing to ECS structure. RESULTS Tracers injected into the caudate nucleus were transported to the ipsilateral frontal and temporal cortices away from the injection points, while both of them injected into the thalamus were only distributed on site. Although the caudate nucleus was closely adjacent to the thalamus, tracer transportation between partitions was not observed. In addition, D* and the λ showed statistically significant differences between partitions. ECS was shown to be a physiologically partitioned system, and its division is characterized by the unique distribution territory and transportation ability of substances located in it. Versican and Tenascin R are possible contributors to the tortuosity of ECS. CONCLUSIONS Tracer-based MRI will improve our understanding of the brain microenvironment, improve the techniques for local delivery of drugs, and highlight brain tissue engineering fields in the future.
背景 本研究评估了一种基于示踪剂的创新磁共振成像（MRI）系统，以可视化示踪剂在深部脑细胞外间隙（ECS）区域的动态运输，并测量运输能力和ECS结构。
材料与方法 选择钆-二乙烯三胺五乙酸（Gd-DTPA）作为示踪剂，并将其注入尾状核和丘脑。观察Gd-DTPA在ECS中的实时动态运输，并通过激光扫描共聚焦显微镜验证结果。利用跨血脑屏障的Transwell分析，进一步简化了修正的扩散方程。计算有效扩散系数D*和曲折度λ。采用免疫组织化学染色和蛋白质印迹分析来研究对ECS结构有贡献的细胞外基质。
结果 注入尾状核的示踪剂从注射点向同侧额叶和颞叶皮质运输，而注入丘脑的示踪剂仅分布在原位。尽管尾状核与丘脑紧密相邻，但未观察到不同分区之间的示踪剂运输。此外，不同分区之间的D*和λ显示出统计学上的显著差异。ECS被证明是一个生理上分区的系统，其划分的特征在于位于其中的物质的独特分布区域和运输能力。多功能蛋白聚糖和腱生蛋白R可能是ECS曲折度的影响因素。
结论 基于示踪剂的MRI将增进我们对脑微环境的理解，改进局部给药技术，并在未来突出脑组织工程领域。
