Clinical evaluation of neuroinflammation in child-onset focal epilepsy: a translocator protein PET study

Abstract

Background Neuroinflammation is associated with various chronic neurological diseases, including epilepsy; however, neuroimaging approaches for visualizing neuroinflammation have not been used in the clinical routine yet. In this study, we used the translocator protein positron emission tomography (PET) with [11C] DPA713 to investigate neuroinflammation in the epileptogenic zone in patients with child-onset focal epilepsy. Methods Patients with intractable focal epilepsy were recruited at the Epilepsy Center of Osaka University; those who were taking any immunosuppressants or steroids were excluded. PET images were acquired for 60 min after intravenous administration of [11C] DPA713. The PET image of [11C] DPA713 was co-registered to individual’s magnetic resonance imaging (MRI), and the standardized uptake value ratio (SUVr) in regions of interest, which were created in non-lesions and lesions, was calculated using the cerebellum as a pseudo-reference region. In the case of epilepsy surgery, the correlation between SUVr in lesions and pathological findings was analyzed. Results Twenty-seven patients (mean age: 11.3 ± 6.2 years, male/female: 17/10) were included in this study. Of these, 85.1% showed increased uptake of [11C] DPA713 in the focal epileptic lesion. Three patients showed epileptic spasms, suggesting partial seizure onset, and all 18 patients with abnormal lesions on MRI were similarly highlighted by significant uptake of [11C] DPA713. DPA713-positive patients had a broad range of etiologies, including focal cortical dysplasia, tumors, infarction, and hippocampal sclerosis. Five out of nine MRI-negative patients showed abnormal [11C] DPA713 uptake. The SUVr of [11C] DPA713 in lesions was significantly higher than that in non-lesions. In seven patients who underwent epilepsy surgery, increased [11C] DPA713 uptake was associated with microglial activation. Conclusions This study indicates that [11C] DPA713 uptake has valuable sensitivity in the identification of epileptic foci in child-onset focal epilepsy, and inflammation is implicated in the pathophysiology in the epileptic foci caused by various etiologies. Further research is required to establish diagnostic tools for identifying focal epileptogenic zones.

[ 18 F]DPA-714 PET Imaging in the Presurgical Evaluation of Patients With Drug-Resistant Focal Epilepsy

“…The AI was widely used in previous work on TSPO imaging. 12,17,18 However, in the case of bilateral anomaly without side predominance, the AI is normal which may be misleading (leading to conclude either to a bilateral epileptogenicity or an absence of fixation in these regions). Moreover ROI analysis is constraint by anatomical features (surface uptake and delineation).…”

“…We compared [ 18 F]FDG and [ 18 F]DPA-714 PET images of 23 patients who had undergone a phase 1 presurgical assessment, using qualitative visual analysis and quantitative analysis, at both the voxel and the regional levels. PET abnormalities (increase in binding for [ 18 F]DPA-714 vs decrease in binding for [ 18 F]FDG) were compared with clinical hypotheses concerning the localization of the EZ based on phase 1 presurgical assessment. The additional value of [ 18 F]DPA-714 PET imaging to [ 18 F]FDG for refining the localization of the EZ was assessed.…”

Extension of microglial activation is associated with epilepsy and cognitive dysfunction in Tuberous sclerosis complex: A TSPO-PET study

“…For attenuation correction, transmission data were acquired using a rotating Cs-137-point source following the emission scan. Based on our previous protocol ( Kagitani-Shimono et al, 2021 ), PET images acquired for 40 to 60 min were used for visual assessment.…”

“…The MRI images were examined for the absence of obvious cerebellar lesions, and DPA713 images were inspected for the absence of abnormal uptake in the cerebellum. To account for inter-participant differences, the standardized uptake value ratio (SUVr) was calculated using the cerebellum as a reference using PMOD 4.1 (PMOD Technologies ltd.) ( Kagitani-Shimono et al, 2021 , Lyoo et al, 2015 ). Then, the SUVr in the regions of interest in the cortical tubers was obtained.…”

“…Patients with temporal lobe epilepsy also showed significant uptake of TSPO in the ipsilateral hippocampus ( Gershen et al, 2015 , Hirvonen et al, 2012 ). In addition, we have previously reported that TSPO-PET detects the epileptogenic foci in children with various etiologies of epilepsy, including TSC, and microglial accumulation in surgical specimens correlated with the regions of uptake in TSPO-PET ( Kagitani-Shimono et al, 2021 ).…”