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Purpose: The purpose of this study was to compare the capabilities of contrast-enhanced fat-suppressed (CE FS) three-dimensional fluid-attenuated inversion recovery (3D FLAIR) brain magnetic resonance imaging (MRI) with those of coronal T2-weighted orbital MRI obtained at 3 Tesla for the diagnosis of optic neuritis (ON)., Materials and Methods: Patients who presented to our center with acute visual loss and underwent MRI examination of the orbits and the brain between November 2014 and February 2020 were retrospectively included. Three radiologists independently and blindly analyzed CE FS 3D FLAIR and coronal T2-weighted images. Disagreements in image interpretation were resolved by consensus with an independent neuroradiologist who was not involved in the initial reading sessions. The primary adjudication criterion for the diagnosis of ON was the presence of an optic nerve hypersignal. Sensitivity, specificity, and accuracy of CE 3D FLAIR brain images were compared with those of coronal T2-weighted orbital images using McNemar test. Artifacts were classified into three categories and compared between the two image sets., Results: A total of 1023 patients were included. There were 638 women and 385 men with a mean age of 42 ± 18.3 (standard deviation) years (age range: 6-92 years). Optic nerve hyperintensities were identified in 375/400 (94%) patients with ON using both 3D FLAIR and coronal T2-weighted images. Sensitivity, specificity, and accuracy of both sequences were 94% (95% CI: 91.3-96.1), 79% (95% CI: 75.5-82.2), and 89% (95% CI: 86.8-90.7), respectively. Optic disc hypersignal was detected in 120/400 patients (30%) using 3D FLAIR compared to 3/400 (0.75%) using coronal T2-weighted images (P < 0.001). Optic radiation hypersignal was observed in 2/400 (0.5%) patients using 3D FLAIR images. Significantly more artifacts (moderate or severe) were observed on coronal T2-weighted images (801/1023; 78%) by comparison with 3D FLAIR images (448/1023; 44%) (P < 0.001)., Conclusion: The performance of 3D FLAIR brain MRI for the diagnosis of ON is not different from that of coronal T2-weighted orbital MRI and its use for optic nerve analysis may be beneficial., Competing Interests: Declaration of competing interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2024 Société française de radiologie. Published by Elsevier Masson SAS. All rights reserved.)