{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T22:26:21Z","timestamp":1787869581954,"version":"build-2784847793"},"reference-count":41,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,6]],"date-time":"2025-12-06T00:00:00Z","timestamp":1764979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: The aim of the study was to compare diagnostic performance of 3D-Double Inversion Recovery (DIR) and 3D-Fluid-Attenuated Inversion Recovery (FLAIR) sequences in the detection of brain lesions in Multiple Sclerosis (MS) patients, especially cortical ones, and to evaluate potential correlation between lesion number and clinical outcome. Methods: From April 2021 to July 2024, 278 MS patients (201 females, 77 males, mean age 47.01 \u00b1 12.668 years) underwent brain MRI in three Italian Institutions using 1.5 T systems; 3D-FLAIR and 3D-DIR sequences were obtained with an identical anatomic position. Clinical disability was evaluated by the expanded disability state score (EDSS). Data analysis was performed using the Wilcoxon test for lesion count differences (primary endpoint), and Chi-square test and Spearman for EDSS correlation (secondary endpoint); a p &lt; 0.05 was considered as statistically significant. Results: A significantly higher total number of lesions was displayed on DIR images (n = 6601) compared with FLAIR (n = 6484) (p &lt; 0.001). The mean number of cortical lesions identified with DIR (1.56 \u00b1 2.767) was significantly higher than the mean number of cortical lesions detected with FLAIR (0.52 \u00b1 1.029) (p &lt; 0.001). Conversely, FLAIR sequences detected a significantly higher mean number of subcortical lesions (9.34 \u00b1 8.663) compared to DIR (8.94 \u00b1 8.415) (p &lt; 0.001). A significant correlation was found between EDSS and the number of juxtacortical and cortical lesions detected with DIR with a p &lt; 0.001. Conclusions: 3D-DIR is superior to 3D-FLAIR in detecting cortical lesions, which are correlated to clinical disability, and it should be implemented for the diagnosis and prognostic evaluation in MS patients.<\/jats:p>","DOI":"10.3390\/diagnostics15243103","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T09:17:36Z","timestamp":1765185456000},"page":"3103","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Superiority of 3D-DIR over 3D-FLAIR in the Detection of Cortical Lesions and Correlation with Disability in Multiple Sclerosis: A Multicenter Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6016-6609","authenticated-orcid":false,"given":"Irene","family":"Grazzini","sequence":"first","affiliation":[{"name":"Unit of Neuroradiology, Department of Diagnostic Imaging, San Donato Hospital, 52100 Arezzo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1509-4121","authenticated-orcid":false,"given":"Davide","family":"Del Roscio","sequence":"additional","affiliation":[{"name":"Unit of Neuroradiology, Department of Diagnostic Imaging, Misericordia Hospital, 58100 Grosseto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0330-4905","authenticated-orcid":false,"given":"Marco","family":"Cirinei","sequence":"additional","affiliation":[{"name":"Unit of Neuroradiology, Department of Diagnostic Imaging, Misericordia Hospital, 58100 Grosseto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4437-872X","authenticated-orcid":false,"given":"Benedetta","family":"Calchetti","sequence":"additional","affiliation":[{"name":"Department of Neurology, San Donato Hospital, 52100 Arezzo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Grammatico","sequence":"additional","affiliation":[{"name":"Department of Neurology, San Donato Hospital, 52100 Arezzo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Spossati","sequence":"additional","affiliation":[{"name":"Department of Technical, Rehabilitation, and Preventive Health Professions, San Donato Hospital, 52100 Arezzo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Malatesti","sequence":"additional","affiliation":[{"name":"Department of Technical, Rehabilitation, and Preventive Health Professions, San Donato Hospital, 52100 Arezzo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9697-1221","authenticated-orcid":false,"given":"Teresa","family":"De Stefano","sequence":"additional","affiliation":[{"name":"Unit of Neuroradiology, Department of Diagnostic Imaging, Misericordia Hospital, 58100 Grosseto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Cuneo","sequence":"additional","affiliation":[{"name":"Unit of Diagnostic and Therapeutic Neuroradiology, Department of Diagnostic Imaging, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Leonini","sequence":"additional","affiliation":[{"name":"Unit of Diagnostic and Therapeutic Neuroradiology, Department of Diagnostic Imaging, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto","family":"Piane","sequence":"additional","affiliation":[{"name":"Unit of Neuroradiology, Department of Diagnostic Imaging, Misericordia Hospital, 58100 Grosseto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3430-1234","authenticated-orcid":false,"given":"Lorenzo","family":"Testaverde","sequence":"additional","affiliation":[{"name":"Unit of Neuroradiology, Department of Diagnostic Imaging, United Hospitals of Livorno, 57124 Livorno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/S0140-6736(08)61620-7","article-title":"Multiple sclerosis","volume":"372","author":"Compston","year":"2008","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1056\/NEJMra1401483","article-title":"Multiple Sclerosis","volume":"378","author":"Reich","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/S1474-4422(08)70191-1","article-title":"Grey matter pathology in multiple sclerosis","volume":"7","author":"Geurts","year":"2008","journal-title":"Lancet Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1002\/ana.24791","article-title":"Neuroinflammatory component of gray matter pathology in multiple sclerosis","volume":"80","author":"Herranz","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1001\/archneurol.2009.174","article-title":"Cortical lesions and atrophy associated with cognitive impairment in relapsing-remitting multiple sclerosis","volume":"66","author":"Calabrese","year":"2009","journal-title":"Arch. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1093\/brain\/awz144","article-title":"Assessment of lesions on magnetic resonance imaging in multiple sclerosis: Practical guidelines","volume":"142","author":"Filippi","year":"2019","journal-title":"Brain"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/j.ejrnm.2014.06.010","article-title":"Added value of double inversion recovery magnetic resonance sequence in detection of cortical and white matter brain lesions in multiple sclerosis","volume":"45","author":"Elnekeidy","year":"2014","journal-title":"Egypt. J. Radiol. Nucl. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1148\/radiol.2019181719","article-title":"Longitudinal Characterization of Cortical Lesion Development and Evolution in Multiple Sclerosis with 7.0-T MRI","volume":"291","author":"Treaba","year":"2019","journal-title":"Radiology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/nrneurol.2010.93","article-title":"Cortical lesions in multiple sclerosis","volume":"6","author":"Calabrese","year":"2010","journal-title":"Nat. Rev. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4162","DOI":"10.19082\/4162","article-title":"Assessment of the diagnostic accuracy of double inversion recovery sequence compared with FLAIR and T2W_TSE in detection of cerebral multiple sclerosis lesions","volume":"9","author":"Abidi","year":"2017","journal-title":"Electron. Physician"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1177\/1352458511406575","article-title":"Imaging the tip of the iceberg: Visualization of cortical lesions in multiple sclerosis","volume":"17","author":"Seewann","year":"2011","journal-title":"Mult. Scler."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1177\/197140091302600201","article-title":"Comparison of double inversion recovery and conventional magnetic resonance brain imaging in patients with multiple sclerosis and relations with disease disability","volume":"26","author":"Vural","year":"2013","journal-title":"Neuroradiol. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1177\/13524585211029860","article-title":"Artificial double inversion recovery images for (juxta)cortical lesion visualization in multiple sclerosis","volume":"28","author":"Bouman","year":"2022","journal-title":"Mult. Scler."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1259\/0007-1285-67-804-1258","article-title":"Technical note: Use of a double inversion recovery pulse sequence to image selectively grey or white brain matter","volume":"67","author":"Redpath","year":"1994","journal-title":"Br. J. Radiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1002\/jmri.1880080305","article-title":"Implementation and evaluation of a new pulse sequence for rapid acquisition of double inversion recovery images for simultaneous suppression of white matter and CSF","volume":"8","author":"Bedell","year":"1998","journal-title":"J. Magn. Reson. Imaging"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s43055-022-00719-x","article-title":"Diagnostic utility of 3D DIR MRI in the estimation of MS lesions overall load with special emphasis on cortical subtypes","volume":"53","author":"Abdelrahman","year":"2022","journal-title":"Egypt. J. Radiol. Nucl. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1007\/s00415-015-7724-5","article-title":"Identification of cortical lesions using DIR and FLAIR in early stages of multiple sclerosis","volume":"262","author":"Kolber","year":"2015","journal-title":"J. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1001\/archneur.64.10.1416","article-title":"Detection of cortical inflammatory lesions by double inversion recovery magnetic resonance imaging in patients with multiple sclerosis","volume":"64","author":"Calabrese","year":"2007","journal-title":"Arch. Neurol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.3174\/ajnr.A0645","article-title":"Improved identification of intracortical lesions in multiple sclerosis with phase-sensitive inversion recovery in combination with fast double inversion recovery MR imaging","volume":"28","author":"Nelson","year":"2007","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_21","first-page":"54","article-title":"Double inversion recovery brain imaging at 3T: Diagnostic value in the detection of multiple sclerosis lesions","volume":"28","author":"Wattjes","year":"2007","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1186\/s43055-019-0057-0","article-title":"Diagnostic accuracy of double inversion recovery in delineation of multiple sclerosis lesions and its clinical correlation with expanded disability scoring system","volume":"50","author":"Hamed","year":"2019","journal-title":"Egypt. J. Radiol. Nucl. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S1474-4422(21)00095-8","article-title":"2021 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI in patients with multiple sclerosis","volume":"20","author":"Wattjes","year":"2021","journal-title":"Lancet Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1177\/1352458508094644","article-title":"3D MPRAGE improves classification of cortical lesions in multiple sclerosis","volume":"14","author":"Nelson","year":"2008","journal-title":"Mult. Scler."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.msard.2013.10.002","article-title":"Is 3D MPRAGE better than the combination DIR\/PSIR for cortical lesion detection at 3T MRI?","volume":"3","author":"Nelson","year":"2014","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Favaretto, A., Poggiali, D., Lazzarotto, A., Rolma, G., Causin, F., and Gallo, P. (2015). The Parallel Analysis of Phase Sensitive Inversion Recovery (PSIR) and Double Inversion Recovery (DIR) Images Significantly Improves the Detection of Cortical Lesions in Multiple Sclerosis (MS) since Clinical Onset. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0127805"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1995","DOI":"10.3174\/ajnr.A5815","article-title":"Detection of Leukocortical Lesions in Multiple Sclerosis and Their Association with Physical and Cognitive Impairment: A Comparison of Conventional and Synthetic Phase-Sensitive Inversion Recovery MRI","volume":"39","author":"Forslin","year":"2018","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s43055-020-00298-9","article-title":"Comparative study between double inversion recovery (DIR) and fluid-attenuated inversion recovery (FLAIR) MRI sequences for detection of cerebral lesions in multiple sclerosis","volume":"51","author":"Elkholy","year":"2020","journal-title":"Egypt. J. Radiol. Nucl. Med."},{"key":"ref_29","first-page":"23","article-title":"Efficiency of double inversion recovery (DIR) sequence in the evaluation of supratentorial cortical lesions in multiple sclerosis","volume":"16","author":"Ertan","year":"2018","journal-title":"J. Neuroquantol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1212\/WNL.0000000000001186","article-title":"Cervical cord lesion load is associated with disability independently from atrophy in MS","volume":"84","author":"Kearney","year":"2015","journal-title":"Neurology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1136\/jnnp-2023-331799","article-title":"Prognostic value of spinal cord lesion measures in early relapsing-remitting multiple sclerosis","volume":"95","author":"Lauerer","year":"2024","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.3174\/ajnr.A5329","article-title":"Pre- and Postcontrast 3D Double Inversion Recovery Sequence in Multiple Sclerosis: A Simple and Effective MR Imaging Protocol","volume":"38","author":"Eichinger","year":"2017","journal-title":"AJNR Am. J. Neuroradiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.diii.2023.04.009","article-title":"Improved detection of juxtacortical lesions using highly accelerated double inversion-recovery MRI in patients with multiple sclerosis","volume":"104","author":"Lespagnol","year":"2023","journal-title":"Diagn. Interv. Imaging"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1097\/RLI.0000000000000550","article-title":"Acceleration of Double Inversion Recovery Sequences in Multiple Sclerosis With Compressed Sensing","volume":"54","author":"Eichinger","year":"2019","journal-title":"Investig. Radiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"103065","DOI":"10.1016\/j.nicl.2022.103065","article-title":"Role of artificial intelligence in MS clinical practice","volume":"35","author":"Bonacchi","year":"2022","journal-title":"Neuroimage Clin."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1097\/RLI.0000000000000640","article-title":"Deep-learning generated synthetic double inversion recovery images improve multiple sclerosis lesion detection","volume":"55","author":"Finck","year":"2020","journal-title":"Investig. Radiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"014005","DOI":"10.1117\/1.JMI.6.1.014005","article-title":"Fluid-attenuated inversion recovery MRI synthesis from multisequence MRI using three-dimensional fully convolutional networks for multiple sclerosis","volume":"6","author":"Wei","year":"2019","journal-title":"J. Med. Imaging"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e221425","DOI":"10.1148\/radiol.221425","article-title":"Multicenter Evaluation of AI-generated DIR and PSIR for Cortical and Juxtacortical Multiple Sclerosis Lesion Detection","volume":"307","author":"Bouman","year":"2023","journal-title":"Radiology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.media.2012.09.004","article-title":"Review of automatic segmentation methods of multiple sclerosis white matter lesions on conventional magnetic resonance imaging","volume":"17","author":"Francis","year":"2013","journal-title":"Med. Image Anal."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1177\/1352458520966298","article-title":"The emerging role of artificial intelligence in multiple sclerosis imaging","volume":"28","author":"Afzal","year":"2020","journal-title":"Mult. Scler."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.compmedimag.2018.10.002","article-title":"Survey of automated multiple sclerosis lesion segmentation techniques on magnetic resonance imaging","volume":"70","author":"Danelakis","year":"2018","journal-title":"Comput. Med. Imaging Graph."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/24\/3103\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T09:30:03Z","timestamp":1765186203000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/24\/3103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,6]]},"references-count":41,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["diagnostics15243103"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15243103","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,6]]}}}