PURPOSE: To prospectively compare the depiction of intracortical lesions by using multislab three-dimensional (3D) double inversion-recovery (DIR), multislab 3D fluid-attenuated inversion-recovery (FLAIR), and T2-weighted spin-echo (SE) magnetic resonance (MR) imaging in patients with multiple sclerosis. MATERIALS AND METHODS: Local ethics review board approval and informed consent were obtained. Conventional T2-weighted SE and multislab 3D FLAIR and DIR images were acquired in 10 patients with multiple sclerosis (five women, five men) and 11 age-matched healthy control subjects (seven women, four men). Mean age was 40 years (range, 25-54 years) in patients and 34 years (range, 24-55 years) in control subjects. Lesions were classified according to seven anatomic regions: intracortical, mixed white matter-gray matter, juxtacortical, deep gray matter, periventricular white matter, deep white matter, and infratentorial lesions. The numbers of lesions per category were compared between techniques (Dunnett-corrected analysis of variance). Gain or loss (with 95% confidence intervals [CIs]) of numbers of lesions detected at 3D DIR imaging was calculated in comparison with those detected at T2-weighted SE and 3D FLAIR imaging. RESULTS: Total number of lesions did not differ between 3D DIR and 3D FLAIR sequences, but the 3D DIR sequence showed a gain of 21% (95% CI: 4%, 41%) in comparison with the T2-weighted SE sequence. Because of high gray matter-white matter contrast, DIR images depicted more intracortical lesions (80 lesions in 10 patients) than both SE (10 lesions) and FLAIR (31 lesions) images; gains with DIR were 538% (95% CI: 191%, 1297%) and 152% (95% CI: 15%, 453%) compared with SE and FLAIR, respectively. Only four intracortical lesions were detected in control subjects. Also, DIR imaging enabled a better definition of mixed white matter-gray matter lesions because of greater contrast between the lesion and its surroundings. CONCLUSION: MR imaging with 3D DIR enables increased intracortical lesion detection in the multiple sclerosis brain, as well as improved distinction between juxtacortical and white matter-gray matter lesions. © RSNA, 2005.