Reduced synaptic vesicle protein 2A binding in temporal lobe epilepsy: A [¹¹C]UCB‐J positron emission tomography study

Abstract

In this positron emission tomography (PET) study with [ 11 C]UCB-J, we evaluated synaptic vesicle glycoprotein 2A (SV2A) binding, which is decreased in resected brain tissues from epilepsy patients, in subjects with temporal lobe epilepsy (TLE) and compared the regional binding pattern to [ 18 F]fluorodeoxyglucose (FDG) uptake. Methods: Twelve TLE subjects and 12 control subjects were examined. Regional [ 11 C]UCB-J binding potential (BP ND) values were estimated using the centrum semiovale as a reference region. [ 18 F]FDG uptake in TLE subjects was quantified using mean radioactivity values. Asymmetry in outcome measures was assessed by comparison of ipsilateral and contralateral regions. Partial volume correction (PVC) with the iterative Yang algorithm was applied based on the FreeSurfer segmentation. Results: In 11 TLE subjects with medial temporal lobe sclerosis (MTS), the hippocampal volumetric asymmetry was 25 ± 11%. After PVC, [ 11 C]UCB-J BP ND asymmetry indices were 37 ± 19% in the hippocampus, with very limited asymmetry in other brain regions. Reductions in [ 11 C]UCB-J BP ND values were restricted to the sclerotic hippocampus when compared to control subjects. The corresponding asymmetry in hippocampal [ 18 F]FDG uptake was 22 ± 7% and correlated with that of [ 11 C]UCB-J BP ND across subjects (R 2 = .38). Hippocampal asymmetries in [ 11 C] UCB-J binding were 1.7-fold larger than those of [ 18 F]FDG uptake. Significance: [ 11 C]UCB-J binding is reduced in the seizure onset zone of TLE subjects with MTS. PET imaging of SV2A may be a promising biomarker approach in the presurgical selection and evaluation of TLE patients and may improve the sensitivity of molecular imaging for seizure focus detection.

Identifying brain networks in synaptic density PET (11C-UCB-J) with independent component analysis

“…This approach may be of interest in studies of neurodegenerative and psychiatric disorders. Previously, we and others have reported differences in synaptic density as measured with 11 C-UCB-J PET in epilepsy, Alzheimer’s disease, PTSD, Parkinson’s disease and psychiatric disorders ( Chen et al, 2018 ; D’Souza et al, 2020 ; Finnema et al, 2020 , 2016 ; Holmes et al, 2019 ; Matuskey et al, 2020 ; Onwordi et al, 2020 ). As well, multi-modality approaches utilizing ICA have already been applied to find altered network integrity in dementing disorders ( Ripp et al, 2020 ).…”

TSPO PET upregulation predicts epileptic phenotype at disease onset independently from chronic TSPO expression in a rat model of temporal lobe epilepsy

“…In the present study, we have demonstrated a declined hippocampal synaptic density during chronic epilepsy, however, it was mainly restricted to the CA1 layer and not associated with seizure frequency. While such focal reduction might be difficult to detect in vivo given the spatial resolution of microPET cameras (range of 0.8–1.5 mm), the potential application of SV2A PET imaging as a non-invasive marker for epilepsy is supported by recent work demonstrating its applicability in rodents ( Bertoglio et al, 2019b , Thomsen et al, 2020 ), evidence of reduced synaptic density in KASE rats during the progression of epilepsy ( Serrano et al, 2020 ) and further corroborated by the observation that SV2A PET can detect the epileptogenic focus in patients with refractory TLE ( Finnema et al, 2016 , Finnema et al, 2020 ).…”

Preliminary In Vivo Evidence of Reduced Synaptic Density in Human Immunodeficiency Virus (HIV) Despite Antiretroviral Therapy

“…Although SV2A PET imaging is a recent development, it has already been used to study synaptic density in Alzheimer’s disease [ 32 ], depression [ 33 ], post-traumatic stress disorder (PTSD) [ 33 ], Parkinson’s disease (PD) [ 34 ], schizophrenia [ 35 ], and epilepsy [ 36 ]. Among other notable findings, one study found large reductions in synaptic density in the seizure onset zone (SOZ) relative to the contralateral side, providing a biomarker for accurately identifying the SOZ in the presurgical evaluation of these patients.…”