Altered Coupling Between Resting-state Glucose Metabolism and Functional Activity in Medial Temporal Lobe Epilepsy with Hippocampal Sclerosis: A hybrid PET/MR study

Objectives: Altered functional activities and hypometabolism have been found within the ipsilateral hippocampal network in medial temporal lobe epilepsy patients with hippocampal sclerosis (mTLE-HS). Hybrid PET/MR scanners provide opportunities to explore the relationship between resting-state energy consumption and functional activities, but whether the repeated seizures could disturb the bioenergetic coupling and its relation with seizure outcome is not known in patients with mTLE-HS. In this prospective study, twenty-six patients with mTLE-HS and twenty-six healthy controls from March 2016 to May 2018 were performed a hybrid PET/MR imaging (18F-FDG PET and resting-state functional MRI (rs-fMRI) scans). Between-group differences in standardized uptake value ratio (SUVR) and rs-fMRI derived metrics (regional homogeneity (ReHo), fractional amplitude of low frequency fluctuations (fALFF)) were evaluated by two-sample t test, controlling for age, sex, the ipsilateral hippocampus volume. The ipsilateral hippocampal network was identified based on rs-fMRI data by region of interest (ROI)-wise analysis. The voxel-wise spatial correlations were explored between SUVR and ReHo, fALFF within the hippocampal network. We further evaluated the relationship between altered coupling pattern and surgical outcome(Engel class). Spatial correlations between SUVR and fMRI-derived metrics were significantly higher in patients with mTLE-HS compared with healthy controls (fALFF/SUVR, p<0.001; ReHo/SUVR, p=0.022). Altered fALFF/SUVR coupling has significant differences among three outcome groups. These findings showed the bioenergetic decoupling within the hippocampal network and its relation with seizure outcome, which may provide novel insights into pathogenesis of mTLE-HS and potential noninvasive maker for the selection of epilepsy surgery patients.