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Updated: May 26, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Postmortem verification of MS cortical lesion detection with 3D DIR
A Seewann1, E-J Kooi, S D Roosendaal
1Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
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 >3-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.
Insights
3D double inversion recovery (DIR) MRI shows higher sensitivity and specificity for detecting multiple sclerosis (MS) cortical lesions (CLs) compared to 3D fluid-attenuated inversion recovery (FLAIR) MRI in postmortem studies.
Area of Science:
- Neurology
- Radiology
- Pathology
Background:
- Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system.
- Cortical lesions (CLs) are a significant hallmark of MS pathology.
- Accurate detection of CLs is crucial for understanding MS progression and for developing effective treatments.
Purpose of the Study:
- To evaluate the sensitivity and specificity of 3D double inversion recovery (DIR) MRI.
- To compare 3D DIR with 3D fluid-attenuated inversion recovery (FLAIR) MRI for detecting MS cortical lesions.
- To validate MRI findings against histopathology using postmortem brain samples.
Main Methods:
- Acquisition of 3D DIR and 3D FLAIR MRI sequences on fresh brain samples from 14 MS patients.
- Prospective and retrospective scoring of CLs by experienced raters blinded to histopathology.
- Classification of lesions as intracortical or mixed gray matter (GM)-white matter, and scoring of deep GM lesions.
- Direct comparison of MRI findings with detailed histopathological analysis.
Main Results:
- 3D DIR demonstrated a 1.6-fold higher sensitivity for MS CLs than 3D FLAIR (18% vs. 11.5%), improving to 37% with retrospective scoring (2.0-fold higher).
- Sensitivity for mixed GM-white matter lesions was 83% for 3D DIR versus 65% for 3D FLAIR, improving to 96% and 91% respectively with retrospective scoring.
- 3D DIR detected over twice as many purely intracortical lesions as 3D FLAIR, with this ratio increasing to over threefold upon retrospective scoring.
- The specificity of 3D DIR for MS CLs was determined to be 90%.
Conclusions:
- 3D DIR MRI is a highly pathologically specific imaging technique for MS.
- 3D DIR exhibits superior sensitivity in detecting MS cortical lesions compared to 3D FLAIR.
- This postmortem study validates 3D DIR as a valuable tool for MS research and potentially clinical diagnosis.
