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

doi:10.1002/jmri.28921

DOI: 10.1002/jmri.28921 ISSN: 1053-1807

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

Hao Li, Xunrong Luo, Kai Qi, Yijie Lv, Junnan Kan, Changfeng Yang, Xiaoqian Lin, Jin Tao, Wei Zhang, Yan Liu, Kang Rong, Ailing Wang, Zhongde Jiang, Xianglin Li

Radiology, Nuclear Medicine and imaging

Show PDF Cite

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.

Outline