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

Abstract

BackgroundGlutamate 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.PurposeTo investigate the GluCEST changes in hippocampus in MDD and the relationship between glutamate and hippocampal subregional volumes.Study TypeCross‐sectional.SubjectsThirty‐two MDD patients (34% males; 22.03 ± 7.21 years) and 47 healthy controls (HCs) (43% males; 22.00 ± 3.28 years).Field Strength/Sequence3.0 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 (1H MRS).AssessmentGluCEST data were quantified by magnetization transfer ratio asymmetry (MTRasym) analysis and assessed by the relative concentration of 1H MRS‐measured glutamate. FreeSurfer was used for hippocampus segmentation.Statistical TestsThe independent sample t test, Mann–Whitney U test, Spearman's correlation, and partial correlation analysis were used. P < 0.05 was considered statistically significant.ResultsIn 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 ConclusionGluCEST 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 Evidence2Technical EfficacyStage 1