GluCEST Imaging and Structural Alterations of the Bilateral Hippocampus in First-Episode and Early-Onset Major Depression Disorder

Abstract

Background: Glutamate dysregulation is one of the key pathogenic mechanisms of major depressive disorder (MDD), and glutamate chemical exchange saturation transfer (GluCEST) has been used for glutamate measurement in some brain diseases but rarely in depression.

Purpose: To investigate the GluCEST changes in hippocampus in MDD and the relationship between glutamate and hippocampal subregional volumes.

Study type: Cross-sectional.

Subjects: Thirty-two MDD patients (34% males; 22.03 ± 7.21 years) and 47 healthy controls (HCs) (43% males; 22.00 ± 3.28 years).

Field strength/sequence: 3.0 T; magnetization prepared rapid gradient echo (MPRAGE) for three-dimensional T1-weighted images, two-dimensional turbo spin echo GluCEST, and multivoxel chemical shift imaging (CSI) for proton magnetic resonance spectroscopy (¹ H MRS).

Assessment: GluCEST data were quantified by magnetization transfer ratio asymmetry (MTR_asym ) analysis and assessed by the relative concentration of ¹ H MRS-measured glutamate. FreeSurfer was used for hippocampus segmentation.

Statistical tests: The independent sample t test, Mann-Whitney U test, Spearman's correlation, and partial correlation analysis were used. P < 0.05 was considered statistically significant.

Results: In the left hippocampus, GluCEST values were significantly decreased in MDD (2.00 ± 1.08 [MDD] vs. 2.62 ± 1.41 [HCs]) and showed a significantly positive correlation with Glx/Cr (r = 0.37). GluCEST values were significantly positively correlated with the volumes of CA1 (r = 0.40), subiculum (r = 0.40) in the left hippocampus and CA1 (r = 0.51), molecular_layer_HP (r = 0.50), GC-ML-DG (r = 0.42), CA3 (r = 0.44), CA4 (r = 0.44), hippocampus-amygdala-transition-area (r = 0.46), and the whole hippocampus (r = 0.47) in the right hippocampus. Hamilton Depression Rating Scale scores showed significantly negative correlations with the volumes of the left presubiculum (r = -0.40), left parasubiculum (r = -0.47), and right presubiculum (r = -0.41).

Data conclusion: GluCEST can be used to measure glutamate changes and help to understand the mechanism of hippocampal volume loss in MDD. Hippocampal volume changes are associated with disease severity.

Level of evidence: 2 TECHNICAL EFFICACY: Stage 1.

Keywords: GluCEST; glutamate; hippocampal subfields; hippocampus; major depressive disorder.