Hippocampal Glutamate Levels and Their Correlation With Subregion Volume in School‐Aged Children With MRI‐Negative Epilepsy: A Preliminary Study

Abstract

BackgroundAbnormal levels of glutamate constitute a key pathophysiologic mechanism in epilepsy. The use of glutamate chemical exchange saturation transfer (GluCEST) imaging to measure glutamate levels in pediatric epilepsy is rarely reported in research.PurposeTo investigate hippocampal glutamate level variations in pediatric epilepsy and the correlation between glutamate and hippocampal subregional volumes.Study TypeCross‐sectional, prospective.SubjectsA total of 38 school‐aged pediatric epilepsy patients with structurally normal MRI as determined by at least two independent radiologists (60% males; 8.7 ± 2.5 years; including 20 cases of focal pediatric epilepsy [FE] and 18 cases of generalized pediatric epilepsy [GE]) and 17 healthy controls (HC) (41% males; 9.0 ± 2.5 years).Field Strength/Sequence3.0 T; 3D magnetization prepared rapid gradient echo (MPRAGE) and 2D turbo spin echo GluCEST sequences.AssessmentThe relative concentration of glutamate was calculated through pixel‐wise magnetization transfer ratio asymmetry (MTRasym) analysis of the GluCEST data. Hippocampal subfield volumes were computed from MPRAGE data using FreeSurfer.Statistical TestsThis study used t tests, one‐way analysis of variance, Kruskal–Wallis tests, and Pearson correlation analysis. P < 0.05 was considered statistically significant.ResultsThe MTRasym values of both the left and right hippocampi were significantly elevated in GE (left: 2.51 ± 0.23 [GE] vs. 2.31 ± 0.12 [HCs], right: 2.50 ± 0.22 [GE] vs. 2.27 ± 0.22 [HCs]). The MTRasym values of the ipsilateral hippocampus were significantly elevated in FE (2.49 ± 0.28 [ipsilateral] vs. 2.29 ± 0.16 [HCs]). The MTRasym values of the ipsilateral hippocampus were significantly increased compared to the contralateral hippocampus in FE (2.49 ± 0.28 [ipsilateral] vs. 2.35 ± 0.34 [contralateral]). No significant differences in hippocampal volume were found between different groups (left hippocampus, P = 0.87; right hippocampus, P = 0.87).Data ConclusionGluCEST imaging have potential for the noninvasive measurement of glutamate levels in the brains of children with epilepsy.Level of Evidence2Technical EfficacyStage 1