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Background Technical improvements in magnetic resonance imaging (MRI) acquisition, such as higher field strength and optimized sequences, lead to better multiple sclerosis (MS) lesion detection and characterization. Multiplication of 3D-FLAIR with 3D-T2 sequences (FLAIR 2 ) results in isovoxel images with increased contrast-to-noise ratio, increased white–gray-matter contrast, and improved MS lesion visualization without increasing MRI acquisition time. The current study aims to assess the potential of 3D-FLAIR 2  in detecting cortical/leucocortical (LC), juxtacortical (JC), and white matter (WM) lesions. Objective To compare lesion detection of 3D-FLAIR 2  with state-of-the-art 3D-T2-FLAIR and 3D-T2-weighted images. Methods We retrospectively analyzed MRI scans of thirteen MS patients, showing previously noted high cortical lesion load. Scans were acquired using a 3 T MRI scanner. WM, JC, and LC lesions were manually labeled and manually counted after randomization of 3D-T2, 3D-FLAIR, and 3D-FLAIR 2  scans using the ITK-SNAP tool. Results LC lesion visibility was significantly improved by 3D-FLAIR 2  in comparison to 3D-FLAIR (4 vs 1;  p  = 0.018) and 3D-T2 (4 vs 1;  p  = 0.007). Comparing LC lesion detection in 3D-FLAIR 2  vs. 3D-FLAIR, 3D-FLAIR 2  detected on average 3.2 more cortical lesions (95% CI − 9.1 to 2.8). Comparing against 3D-T2, 3D-FLAIR 2  detected on average 3.7 more LC lesions (95% CI 3.3–10.7). Conclusions 3D-FLAIR 2  is an easily applicable time-sparing MR post-processing method to improve cortical lesion detection. Larger sampled studies are warranted to validate the sensitivity and specificity of 3D-FLAIR 2 .

FLAIR2 post-processing: improving MS lesion detection in standard MS imaging protocols