Abstract: Objective： To investigate the application of the optical magnetic bimodal molecular probe Gd-DO3A-ethylthiouret-fluorescein isothiocyanate (Gd-DO3A-EAFITC) in brain tissue imaging and brain interstitial space (ISS). Methods: In the study, 24 male SD rats were randomly divided into 3 groups, including magnetic probe group (n=6), optical probe group (n=6) and optical magnetic bimodal probe group (n=12), then the optical magnetic bimodal probe group was divided equally into magnetic probe subgroup (n=6) and optical probe subgroup (n=6). Referencing the brain stereotaxic atlas, the coronal globus pallidus as center level, the probes including gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA), fluorescein isothiocyanate (FITC) and Gd-DO3A-EA-FITC of 2 μL (10 mmol/L) were injected into the caudate nucleus respectively, magnetic resonance imaging (MRI) was performed in the magnetic probe group and magnetic probe subgroup to image the dynamic diffusion and distribution of the probes in the brain ISS, a self-developed brain ISS image processing system was used to measure the diffusion coefficient, clearance, volume fraction and half-time in these two groups. Laser scanning confocal microscope (LSCM) was performed in vitro in the optical probe group and optical probe subgroup for fluorescence imaging at the time points 2 hours after the injection of the probe, and the distribution in the oblique sagittal slice was compared with the result of the first two groups. Results: For the magnetic probe group and magnetic probe subgroup, there were the same imaging results between the probes of Gd-DTPA and Gd-DO3A-EA-FITC. The diffusion parameters of Gd-DTPA and GdDO3A-EA-FITC were as follows: the average diffusion coefficients ［(3.31±0.11)×10-4 mm2/s vs. (3.37±0.15)×10-4 mm2/s, t=0.942, P=0.360］, the clearance ［(3.04±0.37) mmol/L vs. (2.90±0.51) mmol/L, t=0.640, P=0.531］, the volume fractions (17.18%±0.14% vs. 17.31%±0.15%, t=1.961, P=0.068), the half-time ［(86.58±3.31) min vs. (84.61±2.38) min, t=1.412, P=0.177］, the diffusion areas ［(23.25±0.68) mm2 vs. (22.71±1.00) mm2, t=1.100, P=0.297］. The statistical analysis of each brain was made by t test, and the diffusion parameters were not statistically significant. Moreover, for the optical probe group and optical probe subgroup, the diffusion area of Gd-DO3A-EA-FITC ［(22.61±1.16) mm2］ was slightly larger than that of FITC ［(22.10±1.29) mm2］, the statistical analysis of each brain was made by t test, and the diffusion parameters were not statistically significant (t=0.713, P=0.492). Conclusion: Gd-DO3AEA-FITC shows the same imaging results as the traditional GD-DTPA, and it can be used in measuring brain ISS.

Key words: Brain, Contrast media, Molecular probe techniques, Interstitial space, Microscopy, confocal, Magnetic resonance imaging