[Diffusion of fluorescent and magnetic molecular probes in brain interstitial space].
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).


CONCLUSIONS
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.
College of Environment and Chemical Engineering, Dalian University, Liaoning Dalian 116622, China; Peking University Medical and Health Analysis Center, Beijing 100191, China; Beijing Key Lab of Magnetic Resonance Imaging Device and Technique, Beijing 100191, China.
Huai-ye
HY
Li
College of Environment and Chemical Engineering, Dalian University, Liaoning Dalian 116622, China; Peking University Medical and Health Analysis Center, Beijing 100191, China; Beijing Key Lab of Magnetic Resonance Imaging Device and Technique, Beijing 100191, China.
Yue
Y
Zhao
Beijing Key Lab of Magnetic Resonance Imaging Device and Technique, Beijing 100191, China; Department of Radiology,Peking University Third Hospital, Beijing 100191, China.
Long
L
Zuo
Beijing Key Lab of Magnetic Resonance Imaging Device and Technique, Beijing 100191, China; Department of Neurology, Peking University Third Hospital, Beijing 100191, China.
Yu
Y
Fu
Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China.
Nan
N
Li
Peking University Medical and Health Analysis Center, Beijing 100191, China.
Lan
L
Yuan
College of Environment and Chemical Engineering, Dalian University, Liaoning Dalian 116622, China.
Shu-jia
SJ
Zhang
Beijing Key Lab of Magnetic Resonance Imaging Device and Technique, Beijing 100191, China; Department of Radiology,Peking University Third Hospital, Beijing 100191, China.
Hong-bin
HB
Han
D000818:Animals; D001921:Brain; D003287:Contrast Media; D004058:Diffusion; D005453:Fluorescence; D005456:Fluorescent Dyes; D019786:Gadolinium DTPA; D008279:Magnetic Resonance Imaging; D018613:Microscopy, Confocal; D015335:Molecular Probes; D059906:Neuroimaging; D051381:Rats
D003287:Contrast Media; D005456:Fluorescent Dyes; D015335:Molecular Probes; D019786:Gadolinium DTPA