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

Abstract

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 (¹ H 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 ¹ H 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 ¹ H 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 (R² = 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.

Level of evidence: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1866-1872.

Keywords: chemical exchange saturation transfer; glutamate; proton magnetic resonance spectroscopy; sleep disturbance.