Epilepsy, one of the most common neurological disorders, is a chronic and recurrent disorder of the brain characterized by unprovoked seizures. Unfortunately, conventional diagnostic methods are limited due to the difficulties of precise localization of the epileptogentic zone. Here, we introduce the calibrated functional MRI (fMRI) to calculate the oxygen to glucose index (OGI) with a combined PET/MR system. With this approach we were able to observe large decreases in relative OGI within the affected hemisphere of epileptic patients. Our method, if proven to locate epileptic foci better than glucose-PET methods alone, will represent an important new diagnostic tool for epilepsy.