{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T12:34:22Z","timestamp":1793795662880,"version":"4.6.1"},"reference-count":40,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,5,31]],"date-time":"2021-05-31T00:00:00Z","timestamp":1622419200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000156","name":"Fonds de Recherche du Qu\u00e9bec - Sant\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000156","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000034","name":"Institute of Neurosciences, Mental Health and Addiction","doi-asserted-by":"publisher","award":["MOP\u2010115131"],"award-info":[{"award-number":["MOP\u2010115131"]}],"id":[{"id":"10.13039\/501100000034","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000034","name":"Institute of Neurosciences, Mental Health and Addiction","doi-asserted-by":"publisher","award":["MOP\u201093614"],"award-info":[{"award-number":["MOP\u201093614"]}],"id":[{"id":"10.13039\/501100000034","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001454","name":"American Epilepsy Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001454","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Previous positron emission tomography (PET) studies using [<jats:sup>11<\/jats:sup>C]ABP688 show reduced metabotropic glutamate receptor type 5 (mGluR5) allosteric binding site availability in the epileptogenic hippocampus of mesial temporal lobe epilepsy (MTLE) patients. However, the link between mGluR5 abnormalities and postsurgical outcomes remains unclear. Here, we test whether reduced PET [<jats:sup>11<\/jats:sup>C]ABP688 binding in cornu ammonis (CA) sectors more vulnerable to glutamatergic excitotoxicity relates to surgical outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We obtained magnetic resonance imaging (MRI) and [<jats:sup>11<\/jats:sup>C]ABP688\u2010PET from 31 unilateral MTLE patients and 30 healthy controls. MRI hippocampal subfields were segmented using FreeSurfer. To respect the lower PET special resolution, MRI\u2010derived anatomical subfields were combined into CA1\u20133, CA4\/dentate gyrus, and Subiculum. Partial volume corrected [<jats:sup>11<\/jats:sup>C]ABP688 nondisplaceable binding potential (BP<jats:sub>ND<\/jats:sub>) values were averaged across each subfield, and <jats:italic>Z<\/jats:italic>\u2010scores were calculated. Subfield [<jats:sup>11<\/jats:sup>C]ABP688\u2010BP<jats:sub>ND<\/jats:sub> was compared between seizure\u2010free and non\u2010seizure\u2010free patients. In addition, we also assessed subfield volumes and [<jats:sup>18<\/jats:sup>F]fluorodeoxyglucose (FDG) uptake in each clinical group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MTLE [<jats:sup>11<\/jats:sup>C]ABP688\u2010BP<jats:sub>ND<\/jats:sub> was reduced in ipsilateral (epileptogenic) CA1\u20133 and CA4\/dentate\u2010gyrus (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001, 95% confidence interval [CI] = .29\u2013.51) compared to controls, with no difference in Subiculum. [<jats:sup>11<\/jats:sup>C]ABP688\u2010BP<jats:sub>ND<\/jats:sub> and subfield volumes were compared between seizure\u2010free (Engel IA, <jats:italic>n<\/jats:italic>\u00a0=\u00a013) and non\u2010seizure\u2010free patients (Engel IC\u2013III, <jats:italic>n<\/jats:italic>\u00a0=\u00a010). In ipsilateral CA1\u20133 only, [<jats:sup>11<\/jats:sup>C]ABP688\u2010BP<jats:sub>ND<\/jats:sub> was lower in seizure\u2010free patients than in non\u2010seizure\u2010free patients (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.012, 95% CI = 1.46\u201311.0) independently of volume. A subset analysis of 12 patients with [<jats:sup>11<\/jats:sup>C]ABP688\u2010PET+[<jats:sup>18<\/jats:sup>F]FDG\u2010PET showed no between\u2010group significant difference in [<jats:sup>18<\/jats:sup>F]FDG uptake, whereas CA1\u20133 [<jats:sup>11<\/jats:sup>C]ABP688\u2010BP<jats:sub>ND<\/jats:sub> remained significantly lower in the seven of 12 seizure\u2010free patients (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.03, 95% CI = \u22123.13 to \u2212.21).<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Reduced mGluR5 allosteric site availability in hippocampal CA1\u20133, measured in vivo by [<jats:sup>11<\/jats:sup>C]ABP688\u2010PET, is associated with postsurgery seizure freedom independent of atrophy or hypometabolism. Information derived from hippocampal CA1\u20133 [<jats:sup>11<\/jats:sup>C]ABP688\u2010PET is a promising imaging biomarker potentially impactful in surgical decisions for MRI\u2010negative\/PET\u2010negative MTLE patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.16952","type":"journal-article","created":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T08:21:57Z","timestamp":1622535717000},"page":"1559-1568","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["In vivo hippocampal cornu ammonis 1\u20133 glutamatergic abnormalities are associated with temporal lobe epilepsy surgery outcomes"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3173-7665","authenticated-orcid":false,"given":"Jack","family":"Lam","sequence":"first","affiliation":[{"name":"Department of Neurology and Neurosurgery Montr\u00e9al Neurological Institute McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M.","family":"DuBois","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Montr\u00e9al Neurological Institute McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared","family":"Rowley","sequence":"additional","affiliation":[{"name":"Translational Neuroimaging Laboratory McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier G.","family":"Rousset","sequence":"additional","affiliation":[{"name":"Division of Nuclear Medicine and Molecular Imaging Johns Hopkins University Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina A.","family":"Gonz\u00e1lez\u2010Ot\u00e1rula","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Montr\u00e9al Neurological Institute McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Paul","family":"Soucy","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Montr\u00e9al Neurological Institute McGill University Montr\u00e9al Qu\u00e9bec Canada"},{"name":"PET Unit McConnell Brain Imaging Centre McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gassan","family":"Massarweh","sequence":"additional","affiliation":[{"name":"PET Unit McConnell Brain Imaging Centre McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffery A.","family":"Hall","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Montr\u00e9al Neurological Institute McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie\u2010Christine","family":"Guiot","sequence":"additional","affiliation":[{"name":"Department of Pathology Montreal Neurological Institute McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Montr\u00e9al Neurological Institute McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Minuzzi","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioural Neurosciences McMaster University Hamilton Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Rosa\u2010Neto","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Montr\u00e9al Neurological Institute McGill University Montr\u00e9al Qu\u00e9bec Canada"},{"name":"Translational Neuroimaging Laboratory McGill University Montr\u00e9al Qu\u00e9bec Canada"},{"name":"PET Unit McConnell Brain Imaging Centre McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1713-1563","authenticated-orcid":false,"given":"Eliane","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery Montr\u00e9al Neurological Institute McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1996.tb01611.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-201X.1996.484231000.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00723.2001"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00579.2001"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092765"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16353"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2006.03.018"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0760-4"},{"issue":"2","key":"e_1_2_9_10_1","first-page":"247","article-title":"Human PET studies of metabotropic glutamate receptor subtype 5 with 11C\u2010ABP688","volume":"48","author":"Ametamey SM","year":"2007","journal-title":"J Nucl Med"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhw249"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25404"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1988.64"},{"key":"e_1_2_9_14_1","first-page":"1","article-title":"Imaging in vivo glutamate fluctuations with [11C]ABP688: a GLT\u20101 challenge with ceftriaxone","volume":"2015","author":"Zimmer E","year":"2014","journal-title":"J Cereb Blood Flow Metab"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1015065626262"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh673"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22160"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)15166-5"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2005.06.003"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410420603"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-015-3167-6"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13709"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/nimg.1998.0395"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00569-X"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2015.04.042"},{"issue":"5","key":"e_1_2_9_26_1","first-page":"904","article-title":"Correction for partial volume effects in PET: principle and validation","volume":"39","author":"Rousset OG","year":"1998","journal-title":"J Nucl Med"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-011-1745-9"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.65"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.25447"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12926"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4492"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1108595"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)90754-5"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2010.12.023"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.21656"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2014.06.024"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20380"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.9b00680"},{"issue":"1","key":"e_1_2_9_39_1","first-page":"390","article-title":"Evaluation of 11C\u2010ABP688 and 18F\u2010FPEB for imaging mGluR5 receptors in the human brain","volume":"52","author":"Kuwabara H","year":"2011","journal-title":"J Nucl Med"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.03.024"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X16673646"}],"container-title":["Epilepsia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.16952","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/epi.16952","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/epi.16952","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T09:52:54Z","timestamp":1693216374000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/epi.16952"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,31]]},"references-count":40,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1111\/epi.16952"],"URL":"https:\/\/doi.org\/10.1111\/epi.16952","archive":["Portico"],"relation":{},"ISSN":["0013-9580","1528-1167"],"issn-type":[{"value":"0013-9580","type":"print"},{"value":"1528-1167","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,31]]},"assertion":[{"value":"2021-01-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}