A novel MRI tracer-based method for measuring water diffusion in the extracellular space of the rat brain

We proposed a novel MRI tracer-based method for the determination of water diffusion in the brain extracellular space (ECS). The measuring system was validated in 32 Sprague Dawley rats. The rats were randomly divided into four groups with different injection sites: 1) caudate nucleus (Cn.); 2) thalamus (T.); 3) cortex (Cor.); and 4) substantia nigra (Sn.). The spin-lattice relaxation time of hydrogen nuclei in water molecules were shortened, which presented as high signal on MRI after the injection of gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) into the rat brain ECS. The enhancement on MRI decreased over time due to the water diffusion and clearance process within the brain ECS. The process was dynamically recorded on a series of magnetic resonance (MR) images. As the increment in signal intensity (ΔSI) could be converted to local Gd-DTPA concentration, the water diffusion parameters were further calculated voxel by voxel based on a modified diffusion model. The most tortuous ECS (λ = 1.77 ± 0.71) was found in Sn. with D∗(Sn) of (2.06 ± 1.01) × 10(-4) mm(2)·s(-1) ( P < 0.05). No statistical difference was demonstrated among D∗(Cn), D∗(T.), and D∗(Cor). with an average D∗ values of (3.28 ± 0.88) × 10(-4) mm(2)·s(-1)( F = 0.18, P > 0.05). By using the tracer-based MRI method, the local diffusion parameters of the brain ECS can be quantitatively measured. The different distribution territories and clearance rates of the tracer in four brain areas indicated that the brain ECS is a physiologically partitioned system.