PurposeInfratentorial lesions in patients with multiple sclerosis are associated with long-term disability. Two-dimensional fluid-attenuated inversion recovery demonstrates poor infratentorial lesion detection when compared to T2-weighted spin echo. Evidence of improved detection with 3D fluid-attenuated inversion recovery has been conflicting. This study compares the infratentorial lesion detection performance, observer performance, and signal and contrast properties between T2-weighted spin echo, 2D, and 3D fluid-attenuated inversion recovery. MethodsTwo board-certified radiologists independently reviewed and counted infratentorial lesions from 85 brain MRIs in patients with clinically definite multiple sclerosis and concurrent 3D, 2D fluid-attenuated inversion recovery, and T2-weighted spin echo sequences. Contrast-to-noise and signal-to-noise ratios were measured for 25 MRIs. Wilcoxon signed-rank test was used for pairwise comparisons of the combined average infratentorial lesion count, contrast-to-noise, and signal-to-noise ratios, and was adjusted for three pairwise comparisons using Bonferroni correction. A corrected p value < 0.05 was considered statistically significant. ResultsThe number of lesions on 3D fluid-attenuated inversion recovery was significantly higher than those on 2D (p < 0.001) and T2-weighted spin echo (p < 0.001). Results of contrast-to-noise and signal-to-noise ratios were overall mixed and predominantly not concordant with lesion count findings, with T2-weighted spin echo demonstrating the highest signal-to-noise ratios and contrast-to-noise ratio of lesion compared with white matter but the lowest contrast-to-noise ratio of lesion compared with gray matter. ConclusionThe 3D fluid-attenuated inversion recovery sequence addresses the disadvantage of poor infratentorial lesion detection on 2D, while still maintaining the advantage over T2-weighted spin echo in the detection of lesions adjacent to the cerebrospinal fluid.