title: Quantification of opioid receptor availability following spontaneous epileptic seizures: correction of [11C]diprenorphine PET data for the partial-volume effect.
abstract: Previous positron emission tomography (PET) studies in refractory temporal lobe epilepsy (TLE) using the non-selective opioid receptor antagonist [(11)C]diprenorphine (DPN) did not detect any changes in mesial temporal structures, despite known involvement of the hippocampus in seizure generation. Normal binding in smaller hippocampi is suggestive of increased receptor concentration in the remaining grey matter. Correction for partial-volume effect (PVE) has not been used in previous DPN PET studies. Here, we present PVE-corrected DPN-PET data quantifying post-ictal and interictal opioid receptor availability in humans with mTLE. Eight paired datasets of post-ictal and interictal DPN PET scans and eleven test/retest control datasets were available from a previously published study on opioid receptor changes in TLE following seizures (Hammers et al., 2007a). Five of the eight participants with TLE had documented hippocampal sclerosis. Data were re-analyzed using regions of interest and a novel PVE correction method (structural functional synergistic-resolution recovery (SFS-RR); (Shidahara et al., 2012)). Data were denoised, followed by application of SFS-RR, with anatomical information derived via precise anatomical segmentation of the participants' MRI (MAPER; (Heckemann et al., 2010)). [(11)C]diprenorphine volume-of-distribution (VT) was quantified in six regions of interest. Post-ictal increases were observed in the ipsilateral fusiform gyri and lateral temporal pole. A novel finding was a post-ictal increase in [(11)C]DPN VT relative to the interictal state in the ipsilateral parahippocampal gyrus, not observed in uncorrected datasets. As for voxel-based (SPM) analyses, correction for global VT values was essential in order to demonstrate focal post-ictal increases in [(11)C]DPN VT. This study provides further direct human in vivo evidence for changes in opioid receptor availability in TLE following seizures, including changes that were not evident without PVE correction. Denoising, resolution recovery and precise anatomical segmentation can extract valuable information from PET studies that would be missed with conventional post-processing procedures.
authors.affiliation: Centre for Neuroscience, Department of Medicine, Imperial College London, London W12 0NN, UK.
authors.forename: Colm J
authors.initials: CJ
authors.lastname: McGinnity
authors.forename: Miho
authors.initials: M
authors.lastname: Shidahara
authors.forename: Maria
authors.initials: M
authors.lastname: Feldmann
authors.forename: Shiva
authors.initials: S
authors.lastname: Keihaninejad
authors.forename: Daniela A
authors.initials: DA
authors.lastname: Riaño Barros
authors.forename: Ioannis S
authors.initials: IS
authors.lastname: Gousias
authors.forename: John S
authors.initials: JS
authors.lastname: Duncan
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: Rolf A
authors.initials: RA
authors.lastname: Heckemann
authors.forename: Federico E
authors.initials: FE
authors.lastname: Turkheimer
authors.forename: Alexander
authors.initials: A
authors.lastname: Hammers
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Koepp
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D004174:Diprenorphine / Q000493:pharmacokinetics*; D004827:Epilepsy / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D021621:Imaging, Three-Dimensional / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011957:Receptors, Opioid / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D011957:Receptors, Opioid; D004174:Diprenorphine