Aerobic glycolysis imaging of epileptic foci during the inter-ictal period

BACKGROUND: In drug-resistant epilepsy, surgical resection of the epileptic focus can end seizures. However, success is dependent on the ability to identify foci locations and, unfortunately, current methods like electrophysiology and positron emission tomography can give contradictory results. During seizures, glucose is metabolized at epileptic foci through aerobic glycolysis, which can be imaged through the oxygen-glucose index (OGI) biomarker. However, inter-ictal (between seizures) OGI changes have not been studied, which has limited its application. METHODS: 18 healthy controls and 24 inter-ictal, temporal lobe epilepsy patients underwent simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) scans. We used [(18)F]fluorodeoxyglucose-PET (FDG-PET) to detect cerebral glucose metabolism, and calibrated functional MRI to acquire relative oxygen consumption. With these data, we calculated relative OGI maps. FINDINGS: While bilaterally symmetrical in healthy controls, we observed, in patients during the inter-ictal period, higher OGI ipsilateral to the epileptic focus than contralateral. While traditional FDG-PET results and temporal lobe OGI results usually both agreed with invasive electrophysiology, in cases where FDG-PET disagreed with electrophysiology, temporal lobe OGI agreed with electrophysiology, and vice-versa. INTERPRETATION: As either our novel epilepsy biomarker or traditional approaches located foci in every case, our work provides promising insights into metabolic changes in epilepsy. Our method allows single-session OGI measurement which can be useful in other diseases. FUNDING: This work was supported by ShanghaiTech University, the Shanghai Municipal Government, the National Natural Science Foundation of China Grant (No. 81950410637) and Shanghai Municipal Key Clinical Specialty (No. shslczdzk03403). F. H. and P. H. were supported by USA National Institute of Health grants (R01 NS-100106, R01 MH-067528).Z. W. was supported by the Key-Area Research and Development Program of Guangdong Province (2019B030335001), National Natural Science Foundation of China (No. 82151303), and National Key R&D Program of China (No. 2021ZD0204002).