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03 September 2017 : Animal Research  

Quantitative Visualization of Dynamic Tracer Transportation in the Extracellular Space of Deep Brain Regions Using Tracer-Based Magnetic Resonance Imaging

Jin Hou1BCDEF, Wei Wang2CG, Xianyue Quan3D, Wen Liang3DF, Zhiming Li1BC, Deji Chen1AFG, Hongbin Han2AG*

DOI: 10.12659/MSM.903010

Med Sci Monit 2017; 23:4260-4268

Abstract

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.

Keywords: Brain, Diffusion, Extracellular Space, Magnetic Resonance Imaging

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750