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While numerous MR sequences have been evaluated individually, their combined performance in clinical routine settings has not been validated histopathologically. This study aimed to determine the detection rate of histopathologically validated cortical lesions using combined assessment of multiple MRI sequences in postmortem in situ imaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Material and methods<\/jats:title>\n                    <jats:p>Five MRI sequences [phase-sensitive inversion recovery (PSIR), double inversion recovery (DIR), fluid-attenuated inversion recovery (FLAIR), 3D-T\u2081, and proton density (PD)\/T\u2082] were acquired at 3\u00a0T for 18 patients with multiple sclerosis using postmortem in situ whole-brain imaging. A total of 66 tissue samples were collected and stained for myelin to identify cortical lesions types I\u2013IV. Cortical lesions were assessed prospectively on MRI (blinded to histopathology) and retrospectively (with histopathological knowledge) using combined sequence evaluation and consensus reading.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Histopathological analysis revealed 115 cortical lesions in 16\/18 patients (4 type I, 43 type II, 61 type III, 7 type IV). Prospective assessment using all MRI sequences combined detected 20\/115 (17.4%) cortical lesions with 100% specificity. The combination of DIR and PSIR sequences showed a 43% relative increase in detection compared to conventional sequences. Retrospective assessment with histopathological knowledge increased detection to 46\/115 (40.0%) lesions, with DIR and PSIR\u00a0in\u00a0 combination providing an 18% relative improvement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Despite using advanced MRI sequences in a highly controlled postmortem setting, cortical lesion detection remains limited at 17.4%. The combination of DIR and PSIR sequences provides the most effective approach, significantly outperforming conventional sequences. These findings establish a reference benchmark for cortical lesion detection rates and highlight persistent limitations of current MRI technology for identifying cortical pathology in multiple sclerosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11547-026-02185-1","type":"journal-article","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T11:26:01Z","timestamp":1770895561000},"page":"826-833","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Whole-brain in situ postmortem MR imaging using a combination of sequences for cortical lesion detection in multiple sclerosis"],"prefix":"10.1007","volume":"131","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2698-4004","authenticated-orcid":false,"given":"Piet M.","family":"Bouman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen J. 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