[Imaging and quantitative measurement of brain extracellular space using MRI Gd-DTPA tracer method].

OBJECTIVE: To observe the diffusion of Gd-DTPA in brain extracellular space (ECS) by magnetic resonance imaging(MRI) and investigate the feasibility of ECS measurement by using MRI tracer method in vivo. METHODS: 2 microL Gd-DTPA was introduced into ECS by caudate nucleus according to stereotaxic atlas in 8 Sprague Dawley(SD) rats (male, 280-320 g). The MRI scans were performed at 1 h, 3 h, 6 h, 9 h and 12 h respectively after administration. MRI appearances of Gd-DTPA diffusion and distribution was observed and compared. The MRI signal enhancement was measured at each time point. The neuroethology assessment was performed after MRI scanning at 12 h. RESULTS: The injection was accurate at the center of the caudate nucleus in 6 rats, while, at the capsula externa in other 2 rats. Gd-DTPA diffused isotropically after it was introduced into caudate nucleus, which spread into lateral cortex at 3 h. The MRI signal enhancement distributed mainly in the middle cerebral artery territory. A significant difference was found between the signal enhancement ratio at 1 h and that at 3 h in the original point of caudate nucleus (t=95.63, P<0.01), and the signal enhancement attenuated following the exponential power function y=1.7886x(-0.1776) (R2=0.94). In 2 rats with the injection point at capsula externa, Gd-DTPA diffused anisotropically along the fiber track of white matter during 1 h to 3 h, and spread into the lateral cortex at 6 h. CONCLUSION: The diffusion and clearance of Gd-DTPA in brain ECS could be monitored and measured quantitatively in vivo by MRI tracer method.

[Measurement of brain extracellular space and its physiological and pathophysiological significance].

The extracellular space (ECS) of brain is defined as an irregular channel which is located in the interstitial tissue outside the plasma membranes of neurons, and occupied by interstitial fluid (ISF). Diffusion in ECS is described by a modified diffusion equation from which several parameters can be calculated, such as the diffusion coefficient (D), the tortuosity (Lambda), the volume fraction (alpha) and the clearance of molecules. Radiolabeled tracers were used for early diffusion measurements. Presently, the real-time iontophoresis (RTI) method is employed for small ions, whereas the integrative optical imaging (IOI) and the magnetic resonance diffusion weighted imaging (DWI) are developed for macromolecules tracers. Extensive experimental studies with such methods show that in normal brain tissue, the volume fraction of ECS typically is about 20% and the tortuosity is 1.6, although there are regional variations. These parameters change with the brain development and in various pathophysiological states. Knowledge of ECS diffusion properties help us to understand extrasynaptic volume transmission to the development of paradigms for drug delivery in brain.