In vivo magnetic resonance imaging of sodium and diffusion in rat glioma at 21.1 T.

Sodium and diffusion magnetic resonance imaging (MRI) in intracranial rat 9L gliomas were evaluated over 6-8 days using the advanced sensitivity of sodium MRI at 21.1 T. Glioma doubling time was 2.4-2.6 days. Glioma sodium signal was detected using the ultra-short echo time of 0.15 ms. The high resolution 3D sodium MRI with pixels of 0.125 μL allowed for minimizing a partial volume effect often relevant to the MRI of low intensity signals. Tumor sodium and diffusion MRI were evaluated for two separate subclones of 9L cells with different resistance to 1,3-bis(2-chloroethyl)-1-nitrosurea detected by pre-surgery assays. In vivo, after implantation, resistant 9L cells created tumors with significantly reduced sodium concentrations (57 ± 3 mM) compared with nonresistant 9L cells (78 ± 3 mM). The corresponding differences in diffusion were less, but also statistically significant. During tumor progression, an increase of glioma sodium concentration was observed in both cell types with a rate of 2.4-5.8 %/day relative to normal brain. Tumor diffusion was not significantly changed at this time, indicative of no alterations in glioma cellularity. Thus, changes in sodium during tumor progression reflect increasing intracellular sodium concentration and mounting metabolic stress. These experiments also demonstrate an enhanced sensitivity of sodium MRI to reflect tumor cell resistance.