Glutamate Chemical Exchange Saturation Transfer (GluCEST) MRI to Evaluate the Rapid Antidepressant Effects of Ketamine in the Hippocampus of Rat Depression Model

Background: Ketamine is a quick acting antidepressant drug, and an accurate detection method is lacking. Ketamine's effects in a rat depression model have not previously been well explored using glutamate chemical exchange saturation transfer (GluCEST). Purpose: To investigate the GluCEST changes of chronic unpredictable mild stress (CUMS) rats after receiving either ketamine or saline injection. Study Type: Randomized animal model trial. Animal Model: 12 CUMS and 6 Sprague–Dawley rats. Divided into three groups: ketamine (N = 6), saline (N = 6), and control (N = 6). Field Strength/Sequence: 7.0 T/the sequence is GluCEST and ¹H MR spectroscopy (MRS). Assessment: The CUMS rats were exposed to different stress factors for 8 weeks. The glutamate concentration in the hippocampus was assessed by the GluCEST,¹H MRS, and the high-performance liquid chromatography (HPLC). Statistical Tests: The t-test, Mann–Whitney U test, and Pearson's correlation. Results: In depression conditions, GluCEST signals were lower in the bilateral hippocampus than in control group. Thirty minutes after ketamine injection, the GluCEST signals in the bilateral hippocampus were higher compared with the saline group (left: 2.99 ± 0.34 [Control] vs. 2.44 ± 0.20 [Saline] vs. 2.85 ± 0.11 [Ketamine]; right: 2.97 ± 0.28 [Control] vs. 2.49 ± 0.25 [Saline] vs. 2.86 ± 0.19 [Ketamine]). In ¹H MRS, significant changes were only observed in the left hippocampus (2.00 ± 0.16 [Control] vs. 1.81 ± 0.09 [Saline] vs. 2.04 ± 0.14 [Ketamine]). Furthermore, HPLC results showed similar trends to those observed in the GluCEST results (left: 2.32 ± 0.22 [Control] vs. 1.96 ± 0.11 [Saline] vs. 2.18 ± 0.11 [Ketamine]; right: 2.35 ± 0.18 [Control] vs. 1.87 ± 0.16 [Saline] vs. 2.09 ± 0.08 [Ketamine]). Data Conclusion: GluCEST can sensitively evaluate the ketamine's antidepressant effects by detecting the fast increase in glutamate concentration. Level of Evidence: 1. Technical Efficacy Stage: 1.

Duke Scholars

Author Xunrong Luo Medicine, Nephrology