Objective: To assess the sensitivity and specificity of 3D double inversion recovery (DIR) MRI for detecting multiple sclerosis (MS) cortical lesions (CLs) using a direct postmortem MRI to histopathology comparison.Methods: Single-slab 3D DIR and 3D fluid-attenuated inversion recovery (FLAIR) images of 56 matched fresh brain samples from 14 patients with chronic MS were acquired at 1.5 T. The images of both sequences were prospectively scored for CLs in consensus by 3 experienced raters who were blinded to histopathology and clinical data. Next, CLs were identified histopathologically and were scored again on 3D DIR and 3D FLAIR (retrospective scoring). CLs were classified as intracortical or mixed gray matter (GM)-white matter lesions. Deep GM lesions were also scored. False-positive scores were noted and, from this, specificity was calculated. Results:We found a sensitivity for 3D DIR to detect MS CLs of 18%, which is 1.6-fold higher than 3D FLAIR (improves to 37% with retrospective scoring; 2.0-fold higher than 3D FLAIR). We detected mixed GM-white matter lesions with a sensitivity of 83% using 3D DIR (65% sensitivity for 3D FLAIR), which improved to 96% upon retrospective scoring (91% for 3D FLAIR). For purely intracortical lesions, 3D DIR detected more than 2-fold more than 3D FLAIR (improved to Ͼ3-fold upon retrospective scoring). The specificity of 3D DIR to MS CLs was found to be 90%. Conclusions:In this postmortem verification study, we have shown that 3D DIR is highly pathologically specific, and more sensitive to CLs than 3D FLAIR in MS. Neurology ® 2012;78:302-308 GLOSSARY BSA ϭ bovine serum albumin; CL ϭ cortical lesion; DIR ϭ double inversion recovery; FLAIR ϭ fluid-attenuated inversion recovery; GM ϭ gray matter; MS ϭ multiple sclerosis; NEX ϭ number of excitations; PBS ϭ phosphate-buffered saline; PLP ϭ proteolipid protein; TE ϭ echo time; TI ϭ inversion time; TR ϭ repetition time; WM ϭ white matter.

Background –  Studies combining postmortem magnetic resonance imaging (MRI) and histopathology have provided important insights into the abnormalities reflected by MRI. Materials and methods –  A short overview of these studies applied to multiple sclerosis (MS) is provided in this review, and the Amsterdam postmortem imaging protocol is specifically highlighted. Conclusion –  Postmortem MRI and histopathology correlation studies have enabled a direct translation of basic pathology in MS to the clinical setting, and have simultaneously served as a biological validation of new MRI techniques.