[In vivo quantitative measurement of diffusion parameters in brain extracellular space of rat by using magnetic...

To develop a novel method of quantitatively measuring the diffusion parameters of brain extracellular space (ECS) by using gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) as the tracer.

Six Sprague Dawley male adult rats were subjected to magnetic resonance (MR) imaging before and after the introduction of 2 μL Gd-DTPA into caudate nucleus (Cn). The enhancement on MR subtracted images was converted to the concentration of Gd-DTPA and an average diffusion rate was calculated pixel by pixel based on the traditional diffusion model.

After the injection, the tracer diffused frontally and laterally with an average diffusion rate of (3.38±1.07)×10(-4) mm(2)/s. It reached at the margin of cortex 2 hours later, and drained into the subarachnoid space 3 hours later. The tortuosity [Λ(Cn (agar))] was 1.31±0.31 with the reference of free diffusion measured in agar gel, which was consistent with the result using real-time iontophoresis-tetramethylammonium method. A more feasible reference was acquired by using a routine MR diffusion weighed imaging and [Λ(Cn (MRI))] was calculated as 3.12±0.73. The tracer was finally clearly out at the end of 12 hours on MR images with a clearance rate constant in Cn of (7.60±4.18)×10(-5)/s.

The biophysical properties of brain ECS can be quantitatively characterized by this newly developed method in living brain, which will enhance our understanding of the micro-environment of neuron and provide a new way to understand cognition and encephalopathy.