TY - JOUR
T1 - Quantification of opioid receptor availability following spontaneous epileptic seizures
T2 - Correction of [11C]diprenorphine PET data for the partial-volume effect
AU - McGinnity, Colm J.
AU - Shidahara, Miho
AU - Feldmann, Maria
AU - Keihaninejad, Shiva
AU - Riaño Barros, Daniela A.
AU - Gousias, Ioannis S.
AU - Duncan, John S.
AU - Brooks, David J.
AU - Heckemann, Rolf A.
AU - Turkheimer, Federico E.
AU - Hammers, Alexander
AU - Koepp, Matthias J.
N1 - Funding Information:
This study was supported by the Medical Research Council Clinical Sciences Centre ( G9901497 ; G108/585 ). Authors affiliated with a are grateful for support from the NIHR Biomedical Research Centre funding scheme .
Funding Information:
FET was supported by the MRC PET Methodology Programme Grant ( G1100809/1 ). AH was supported by an MRC Clinician Scientist Fellowship ( G108/585 ) and the Neurodis Foundation .
Funding Information:
JSD and MJK are supported by the Epilepsy Society , UCL and UCL Hospitals . JD has received fees for organizing symposia for UCB Pharma, Eisai and GE Healthcare.
Funding Information:
CJM was supported by a Medical Research Council Doctoral Training Account (3 + 1) studentship that was awarded by Imperial College London .
Funding Information:
RAH was supported by a research grant from the Dunhill Medical Trust .
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2013/10/1
Y1 - 2013/10/1
N2 - Previous positron emission tomography (PET) studies in refractory temporal lobe epilepsy (TLE) using the non-selective opioid receptor antagonist [11C]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)). [11C]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 [11C]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 [11C]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.
AB - Previous positron emission tomography (PET) studies in refractory temporal lobe epilepsy (TLE) using the non-selective opioid receptor antagonist [11C]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)). [11C]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 [11C]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 [11C]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.
KW - Diprenorphine
KW - Hippocampus
KW - Opioids
KW - PET
KW - Partial-volume
KW - Temporal lobe epilepsy
UR - http://www.scopus.com/inward/record.url?scp=84877908900&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84877908900&partnerID=8YFLogxK
U2 - 10.1016/j.neuroimage.2013.04.015
DO - 10.1016/j.neuroimage.2013.04.015
M3 - Article
C2 - 23597934
AN - SCOPUS:84877908900
VL - 79
SP - 72
EP - 80
JO - NeuroImage
JF - NeuroImage
SN - 1053-8119
ER -