{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T23:02:52Z","timestamp":1788476572484,"version":"build-2803163510"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:00:00Z","timestamp":1706572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Compartmentalized meningeal inflammation is thought to represent one of the key players in the pathogenesis of cortical demyelination in multiple sclerosis. PET targeting the 18\u2005kDa mitochondrial translocator protein (TSPO) is a molecular-specific approach to quantifying immune cell-mediated density in the cortico-meningeal tissue compartment in vivo. This study aimed to characterize cortical and meningeal TSPO expression in a heterogeneous cohort of multiple sclerosis cases using in vivo simultaneous MR-PET with 11C-PBR28, a second-generation TSPO radioligand, and ex vivo immunohistochemistry.<\/jats:p>\n               <jats:p>Forty-nine multiple sclerosis patients (21 with secondary progressive and 28 with relapsing-remitting multiple sclerosis) with mixed or high affinity binding for 11C-PBR28 underwent 90-min 11C-PBR28 simultaneous MR-PET. Tracer binding was measured using 60\u201390\u2005min normalized standardized uptake value ratios sampled at mid-cortical depth and \u223c3\u2005mm above the pial surface. Data in multiple sclerosis patients were compared to 21 age-matched healthy controls. To characterize the nature of 11C-PBR28 PET uptake, the meningeal and cortical lesion cellular expression of TSPO was further described in post-mortem brain tissue from 20 cases with secondary progressive multiple sclerosis and five age-matched healthy donors.<\/jats:p>\n               <jats:p>Relative to healthy controls, patients with multiple sclerosis exhibited abnormally increased TSPO signal in the cortex and meningeal tissue, diffusively in progressive disease and more localized in relapsing-remitting multiple sclerosis. In multiple sclerosis, increased meningeal TSPO levels were associated with increased Expanded Disability Status Scale scores (P = 0.007, by linear regression). Immunohistochemistry, validated using in situ sequencing analysis, revealed increased TSPO expression in the meninges and adjacent subpial cortical lesions of post-mortem secondary progressive multiple sclerosis cases relative to control tissue. In these cases, increased TSPO expression was related to meningeal inflammation. Translocator protein immunostaining was detected on meningeal MHC-class II+ macrophages and cortical-activated MHC-class II+ TMEM119+ microglia. In vivo arterial blood data and neuropathology showed that endothelial binding did not significantly account for increased TSPO cortico-meningeal expression in multiple sclerosis.<\/jats:p>\n               <jats:p>Our findings support the use of TSPO-PET in multiple sclerosis for imaging in vivo inflammation in the cortico-meningeal brain tissue compartment and provide in vivo evidence implicating meningeal inflammation in the pathogenesis of the disease.<\/jats:p>","DOI":"10.1093\/brain\/awae030","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T17:54:10Z","timestamp":1706637250000},"page":"2566-2578","source":"Crossref","is-referenced-by-count":22,"title":["Characterization of cortico-meningeal translocator protein expression in multiple sclerosis"],"prefix":"10.1093","volume":"147","author":[{"given":"Elena","family":"Herranz","sequence":"first","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, MA 02129 ,","place":["USA"]},{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8260-207X","authenticated-orcid":false,"given":"Constantina A","family":"Treaba","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, MA 02129 ,","place":["USA"]},{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0655-9406","authenticated-orcid":false,"given":"Valeria T","family":"Barletta","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, MA 02129 ,","place":["USA"]},{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambica","family":"Mehndiratta","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, MA 02129 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9217-1445","authenticated-orcid":false,"given":"Russell","family":"Ouellette","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, MA 02129 ,","place":["USA"]},{"name":"Department of Clinical Neuroscience, Karolinska Institutet , 141 86 Stockholm ,","place":["Sweden"]},{"name":"Department of Radiology, Karolinska University Hospital , 141 86 Stockholm ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob A","family":"Sloane","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beth Israel Deaconess Medical Center , Boston, MA 02215 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Ionete","sequence":"additional","affiliation":[{"name":"Department of Neurology, UMass Chan Medical School , Worcester, MA 01605 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2648-7625","authenticated-orcid":false,"given":"Suma","family":"Babu","sequence":"additional","affiliation":[{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["USA"]},{"name":"Department of Neurology, Massachusetts General Hospital , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Mastantuono","sequence":"additional","affiliation":[{"name":"Neurology Section, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona , Verona 53593 ,","place":["Italy"]},{"name":"Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , Basel 4058 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Magon","sequence":"additional","affiliation":[{"name":"Pharma Research and Early Development, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd. , Basel 4058 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8026-5265","authenticated-orcid":false,"given":"Marco L","family":"Loggia","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, MA 02129 ,","place":["USA"]},{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["USA"]},{"name":"Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5834-4872","authenticated-orcid":false,"given":"Meena M","family":"Makary","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, MA 02129 ,","place":["USA"]},{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["USA"]},{"name":"Systems and Biomedical Engineering Department, Faculty of Engineering, Cairo University , Giza 12613 ,","place":["Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob M","family":"Hooker","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, MA 02129 ,","place":["USA"]},{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciprian","family":"Catana","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital , Charlestown, MA 02129 ,","place":["USA"]},{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Revere P","family":"Kinkel","sequence":"additional","affiliation":[{"name":"University of California San Diego, Department of Neuroscience , San Diego, CA 92093 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0414-1225","authenticated-orcid":false,"given":"Richard","family":"Nicholas","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Faculty of Medicine, Imperial College London , London SW7 2BX ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric C","family":"Klawiter","sequence":"additional","affiliation":[{"name":"Harvard Medical School , Boston, MA 02115 ,","place":["USA"]},{"name":"Department of Neurology, Massachusetts General Hospital , Boston, MA 02114 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8284-7763","authenticated-orcid":false,"given":"Roberta","family":"Magliozzi","sequence":"additional","affiliation":[{"name":"Neurology Section, Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona , Verona 53593 ,","place":["Italy"]},{"name":"Department of Brain Sciences, Faculty of Medicine, Imperial College London , London SW7 2BX ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Mainero","sequence":"additional","affiliation":[{"name":"Athinoula A. 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