Exploring the Role of TSPO-PET Imaging Among MRI-Negative Patients with Temporal Lobe Epilepsy: From the Perspective of Heterogeneity

<b>Background/Objectives</b>: This study explored the heterogeneous distribution pattern of translocator protein 18kDa (TSPO)-PET/MRI using radioligand [¹⁸F] DPA-714 in temporal lobe epilepsy patients and identified clinical factors influencing imaging outcomes. <b>Methods</b>: The TSPO imaging in individual patient was evaluated with both visual reading and quantitative assessment using an asymmetry index based on cerebellum-normalized standardized uptake values. The association between clinical factors and TSPO imaging outcomes was assessed. Pathological evaluation was conducted in three patients. <b>Results</b>: Twenty-nine TLE patients and ten healthy controls were enrolled. Visual evaluation revealed increased [¹⁸F] DPA-714 uptake in twenty patients as compared to controls, predominantly in a unilateral regional brain, while the remaining nine patients showed visually undetectable uptake of [¹⁸F] DPA-714. Consistently, quantitative analysis revealed that 69% (20/29) patients exhibited at least one brain area with significant asymmetry index, notably in the temporal lobe (85%, 17/20). A high asymmetry index could also be observed in the parietal (13.8%, 4/29) and occipital lobe (17.2%, 5/29). Significant associations were identified between the asymmetry index and seizure frequency (<i>p</i> = 0.045, OR = 7.994), and the interval from last seizure to PET scan (<i>p</i> = 0.033, OR = 6.712). Moreover, we confirmed the pathology in three patients via immunohistochemistry, which underscored the potential of TSPO-PET in detecting minor lesion. <b>Conclusions</b>: TSPO-PET reveals patient-specific and network-level neuroinflammatory heterogeneity in MRI-negative TLE, supporting its potential role as a complementary tool for presurgical evaluation.