Cerebral mapping of glutamate using chemical exchange saturation transfer imaging in a rat model of stress-induced sleep disturbance at 7.0T.

Background Glutamate chemical exchange saturation transfer (GluCEST) imaging has been widely used in brain psychiatric disorders. Glutamate signal changes may help to evaluate the sleep-related disorders, and could be useful in diagnosis. Purpose To evaluate signal changes in the hippocampus and cortex of a rat model of stress-induced sleep disturbance using GluCEST. Study Type Prospective animal study. Animal Model Fourteen male Sprague-Dawley rats. Field Strength/Sequence 7.0T small bore MRI / fat-suppressed, turbo-rapid acquisition with relaxation enhancement (RARE) for CEST, and spin-echo, point-resolved proton MR spectroscopy (H-1 MRS). Assessment Rats were divided into two groups: the stress-induced sleep-disturbance group (SSD, n = 7) and the control group (CTRL, n = 7), to evaluate and compare the cerebral glutamate signal changes. GluCEST data were quantified using a conventional magnetization transfer ratio asymmetry in the left- and right-side hippocampus and cortex. The correlation between GluCEST signal and glutamate concentrations, derived from H-1 MRS, was evaluated. Statistical Analysis Wilcoxon rank-sum test between CEST signals and multiparametric MR signals, Wilcoxon signed-rank test between CEST signals on the left and right hemispheres, and a correlation test between CEST signals and glutamate concentrations derived from H-1 MRS. Results Measured GluCEST signals showed significant differences between the two groups (left hippocampus; 4.23 +/- 0.27% / 5.27 +/- 0.42% [SSD / CTRL, P = 0.002], right hippocampus; 4.50 +/- 0.44% / 5.04 +/- 0.34% [P = 0.035], left cortex; 2.81 +/- 0.38% / 3.56 +/- 0.41% [P = 0.004], and right cortex; 2.95 +/- 0.47% / 3.82 +/- 0.26% [P = 0.003]). GluCEST signals showed positive correlation with glutamate concentrations (R-2 = 0.312; P = 0.038). Data Conclusion GluCEST allowed the visualization of cerebral glutamate changes in rats subjected to sleep disturbance, and may yield valuable insights for interpreting alterations in cerebral biochemical information. Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1866-1872.