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Zuo L.,Peking University | Zuo L.,Beijing Key Laboratory of Magnetic Resonance Imaging Device and Technique | Li K.,Beijing Jishuitan Hospital | Han H.,Peking University
Applied Magnetic Resonance | Year: 2015

Drug delivery to the brain remains a challenge due to the blood–brain barrier. Localized injection of drug therapies represents a promising alternative once the diffusion characteristics of different brain regions have been evaluated. Extracellular space diffusion and interstitial fluid flow of the striatum and thalamus in the rat brain were simultaneously compared using magnetic resonance imaging and the tracer gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA). The diffusion parameters, volume distribution, and half-life time were quantified. While there was extensive diffusion of Gd-DTPA in the striatum, Gd-DTPA was rapidly cleared and had a shorter half-life time in the thalamus. The increased clearance rate and shorter half-life of the tracer in the thalamus were associated with increased expression of Aquaporin-4. The tortuosity of the extracellular space did not show a statistically significant difference between the two regions examined. Our research provides a new reference for brain interstitial drug delivery to treat central nervous system diseases and a better understanding of the brain microenvironment. © 2015, Springer-Verlag Wien.

Li H.,Dalian University | Zhao Y.,Dalian University | Zuo L.,Beijing Key Laboratory of Magnetic Resonance Imaging Device and Technique | Fu Y.,Beijing Key Laboratory of Magnetic Resonance Imaging Device and Technique | And 4 more authors.
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences | Year: 2015

OBJECTIVE: To compare the diffusion properties of fluorescent probes dextran-tetramethylrhodamine (DT) and lucifer yellow CH (LY) and magnetic probe gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) in porous media and to screen out a suitable fluorescent probe for optical imaging of brain interstitial space (ISS).METHODS: Agarose gels sample were divided into DT group, LY group and Gd-DTPA group, and the corresponding molecular probes were imported in each group. The dynamic diffusions of DT and LY in agarose gels at different time points (15, 30, 45, 60, 90, and 120 min) were scanned with laser scanning confocal microscope, the dynamic diffusion of Gd-DTPA was imaged with magnetic resonance imaging. The average diffusion speed of LY were demonstrated to be consistent with those of Gd-DTPA. The LY was introduced into caudate putamen of 18 rats, respectively, the diffusion of LY in the sequential slices of rat brain at different time points (0.5, 1, 2, 3, 7, 11 h) were scanned, and the results were compared with those of rats' brain with Gd-DTPA imported and imaged in vivo with magnetic resonance imaging.RESULTS: The diffusions of the three probes were isotropic in the agarose gels, and the average diffusion speeds of DT, LY and Gd-DTPA were: (0.07±0.02)×10(-2) mm2/s, (1.54±0.47)×10(-2) mm2/s, (1.45±0.50)×10(-2) mm2/s, respectively. The speed of DT was more slower than both LY and Gd-DTPA (ANOVA, F=367.15, P<0.001; Post-Hoc LSD, P<0.001), and there was no significant difference between the speeds of LY and Gd-DTPA (Post-Hoc LSD, P=0.091). The variation tendency of diffusion area of DT was different with both that of LY and that of Gd-DTPA (Bonferroni correction, α=0.0125, P<0.001), and there was no significant difference between LY and Gd-DTPA (Bonferroni correction, α=0.0125, P=0.203), in analysis by repeated measures data of ANOVA. The diffusions of LY and Gd-DTPA were anisotropy in rat caudate putamen,and the average diffusion speeds of LY and Gd-DTPA were: (1.03±0.29)×10(-3) mm2/s, (0.81±0.27)×10(-3) mm2/s, respectively, no significant difference was demonstrated (t=0.759, P=0.490); half-time of single intensity of LY and Gd-DTPA was (2.58±0.04) h, (2.46±0.10) h, respectively, no significant difference was found (t=2.025, P=0.113). The diffusion area ratios between LY and Gd-DTPA in rat caudate putamen was not statistically different at hours 0.5, 1, 2, 3 and 7 (t=2.249, P=0.088; t=2.582, P=0.061; t=1.966, P=0.121; t=0.132, P=0.674; t=0.032, P=0.976), while, a slightly difference was found at 11 h (t=2.917, P=0.043,in analysis by t test).CONCLUSION: LY present the same diffusion property with Gd-DTPA in porous media witch including agarose gels and live rat brain tissue, indicates that LY is a suitable fluorescent probe for optical imaging of brain ISS, and it can be used for microscopic, macro and in vitro measure of brain ISS.

Yang S.,Capital Medical University | Wang Y.,Capital Medical University | Li K.,Beijing Jishuitan Hospital | Tang X.,Capital Medical University | And 6 more authors.
International Journal of Developmental Neuroscience | Year: 2016

The extracellular space (ECS) in the brain provides an extrasynaptic transfer channel among neurons, axons and glial cells. It is particularly important in the early stage after birth, when angiogenesis is not yet complete and the ECS may provide the main pathway for metabolite transport. However, the characteristics of extracellular transport remain unclear. In this study, a novel magnetic resonance imaging (MRI) method was used to perform real-time visualization and quantification of diffusion in the brain ECS of infant (postnatal day 10 (P10)) and adult rats. Using a modified diffusion equation and the linear relationship between the signal intensity and the gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) concentration, diffusion parameters were obtained; these parameters include the effective diffusion coefficient (D*), clearance rate (k'), tortuosity (λ) and the volume fraction of distribution (Vd%). There were significant differences in the diffusion parameters between P10 and adult rats. This finding provides a reference for future treatment of brain diseases using drugs administered via interstitial pathways. © 2016 ISDN

Zhang H.,Peking University | Zhang H.,Beijing Key Laboratory of Magnetic Resonance Imaging Device and Technique | Wang Y.,Hebei Medical University | Chen L.,Peking University | And 3 more authors.
Chinese Journal of Medical Imaging Technology | Year: 2014

In recent years, more and more attention is paid to quantitative analysis of permeability of blood brain barrier (BBB). MR PWI has become one of the most important in vivo research methods of permeability of BBB. The application of permeability of BBB quantitative analysis using MR PWI in intracranial lesions were reviewed in this article. Copyright © 2013 by the Press of Chinese Journal of Medical Imaging Technology.

Han H.B.,Peking University | Han H.B.,Beijing Key Laboratory of Magnetic Resonance Imaging Device and Technique | Li K.,Peking University | Li K.,Beijing Key Laboratory of Magnetic Resonance Imaging Device and Technique | And 5 more authors.
Science China Life Sciences | Year: 2012

The nature of brain interstitial fluid (ISF) has long been a subject of controversy. Most of the previous studies on brain ISF were carried out in vitro. In the present study, a novel method was developed to characterize ISF in the living rat brain by magnetic resonance (MR) imaging using gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) as a tracer. Sprague Dawley rats (n=8) were subjected to MR scanning before and after the introduction of Gd-DTPA into the caudate nucleus. A one-way drainage of brain ISF was demonstrated on the dynamic MR images. According to the traditional diffusion model, the diffusion and clearance rate constants of the tracer within brain extracellular space (ECS) were derived as (3.38+-1.07)×10-4 mm2 s-1 and (7.60±4.18)×10-5 s-1. Both diffusion and bulk flow contributed to the drainage of ISF from the caudate nucleus, which demonstrated an ISF-cerebrospinal fluid confluence in the subarachnoid space at the lateral and ventral surface of the brain cortex at 3 h after the injection. By using this newly developed method, the brain ECS and ISF can be quantitatively measured simultaneously in the living brain, which will enhance the understanding of ISF and improve the efficiency of drug therapy via the brain interstitium. © 2012 The Author(s).

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