Structural changes in glutamate cell swelling followed by multiparametric q-space diffusion MR of excised rat spinal cord

Diffusion in the extracellular and intracellular spaces (ECS and ICS, respectively) was evaluated in excised spinal cords, before and after cell swelling induced by glutamate, by high b-value q-space diffusion MR of specific markers and water. The signal decays of deuterated tetramethylammonium (TMA-d12) chloride, an exogenous marker of the ECS, and N-acetyl aspartate (NAA), an endogenous marker of the ICS, were found to be non-mono-exponential at all diffusion times. The signal decays of these markers were found to depend on the diffusion time and the cell swelling induced by the glutamate. It was found, for example, that the mean displacements of the apparent fast and slow diffusion components of TMA-d12 are 7.21 ± 0.11 and 1.16 ± 0.05 μm, respectively at a diffusion time of 496 ms. After exposure of the spinal cords to 10 mM of glutamate, these values decreased to 6.62 ± 0.13 and 1.01 ± 0.05 μm, respectively. The mean displacement of NAA, however, showed a less pronounced opposite trend and increased after cell swelling induced by exposure to glutamate. q-Space diffusion MR of water was found to be sensitive to exposure to glutamate, and q-space diffusion MRI showed that a more pronounced decrease in the apparent diffusion coefficient and the mean displacement of water is observed in the gray matter (GM) of the spinal cord. All these changes demonstrate that diffusion MR is indeed sensitive to structural changes caused by cell swelling induced by glutamate. Multiparametric high b-value q-space diffusion MR is useful for obtaining microstructural information in neuronal tissues.