ObjectiveThe identification of epileptic lesions is crucial for improving surgical outcomes. Nevertheless, substantial focal cortical dysplasia (FCD) may be invisible on magnetic resonance imaging (MRI). We aimed to characterize the expression pattern of 18-kDa translocator protein (TSPO) in FCD and to evaluate the effectiveness of this inflammation-reflective molecular imaging technique for detecting FCD. MethodsPatients clinically diagnosed with FCD, based on clinical features, interictal electroencephalographic (EEG) findings, and MRI characteristics, underwent positron emission tomography (PET) imaging using 18F-DPA714 and 18F-fluorodeoxyglucose (FDG) tracers. TSPO-PET activation patterns were qualitatively evaluated. Semiquantitative analysis using the Highlight Index (HI) was further performed to investigate its correlation with clinical characteristics. For patients who underwent stereo-EEG (SEEG) monitoring, the site of high-level TSPO-PET activation was compared with the seizure onset zone identified by SEEG. For patients who underwent resection surgery, the relationship between TSPO-PET uptake and histopathological findings was studied. ResultsTwenty-four patients were enrolled. Three groups were identified: MRI-positive with visible high-level TSPO-PET activation (six patients), MRI-negative with visible high-level TSPO-PET activation (thirteen patients), and MRI-positive with invisible low-level TSPO-PET activation (five patients). Regions of high-level TSPO-PET activation showed concordance with ictal discharges in five patients who underwent SEEG. Compared with FDG-PET, TSPO-PET exhibited a more prominent signal against the background (p = .0158). HI was correlated with seizure frequency (p = .0362) and the occurrence of focal to bilateral tonic-clonic seizures (p = .0294), and shorter interval between the TSPO-PET scan and the last seizure was associated with higher TSPO-PET HI (R = -.4323, p = .0349). Postoperative histopathological examination confirmed high-level TSPO-PET activation rates of 3/3 for FCD type IIb and 1/3 for FCD type IIa. SignificanceTSPO-PET activation patterns offer clinical significance for improving surgical outcomes by enhancing FCD detection during presurgical evaluation. Also, our observations offer new insights into the histopathological basis for increased TSPO uptake in humans.