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Updated: Feb 13, 2026

Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Whole-brain in situ postmortem MR imaging using a combination of sequences for cortical lesion detection in multiple
Piet M Bouman1,2, Jeroen J G Geurts3,4, Laura E Jonkman4,5
1MS Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC VUmc, De Boelelaan 1117, 1081HV, Amsterdam, The Netherlands. p.bouman@amsterdamumc.nl.
Purpose:
Cortical lesions are specific for multiple sclerosis but remain challenging to detect using magnetic resonance imaging (MRI). While numerous MR sequences have been evaluated individually, their combined performance in clinical routine settings has not been validated histopathologically. This study aimed to determine the detection rate of histopathologically validated cortical lesions using combined assessment of multiple MRI sequences in postmortem in situ imaging.
Material And Methods:
Five MRI sequences [phase-sensitive inversion recovery (PSIR), double inversion recovery (DIR), fluid-attenuated inversion recovery (FLAIR), 3D-T₁, and proton density (PD)/T₂] were acquired at 3 T for 18 patients with multiple sclerosis using postmortem in situ whole-brain imaging. A total of 66 tissue samples were collected and stained for myelin to identify cortical lesions types I-IV. Cortical lesions were assessed prospectively on MRI (blinded to histopathology) and retrospectively (with histopathological knowledge) using combined sequence evaluation and consensus reading.
Results:
Histopathological analysis revealed 115 cortical lesions in 16/18 patients (4 type I, 43 type II, 61 type III, 7 type IV). Prospective assessment using all MRI sequences combined detected 20/115 (17.4%) cortical lesions with 100% specificity. The combination of DIR and PSIR sequences showed a 43% relative increase in detection compared to conventional sequences. Retrospective assessment with histopathological knowledge increased detection to 46/115 (40.0%) lesions, with DIR and PSIR in combination providing an 18% relative improvement.
Conclusion:
Despite using advanced MRI sequences in a highly controlled postmortem setting, cortical lesion detection remains limited at 17.4%. The combination of DIR and PSIR sequences provides the most effective approach, significantly outperforming conventional sequences. These findings establish a reference benchmark for cortical lesion detection rates and highlight persistent limitations of current MRI technology for identifying cortical pathology in multiple sclerosis.
Insights
Detecting multiple sclerosis cortical lesions with MRI remains difficult, even with advanced sequences. Combining Double Inversion Recovery (DIR) and Phase-Sensitive Inversion Recovery (PSIR) MRI sequences offers the best detection rates but still has limitations.
Area of Science:
- Neuroimaging
- Neuropathology
- Multiple Sclerosis Research
Background:
- Cortical lesions are a hallmark of multiple sclerosis (MS).
- Detecting MS-related cortical lesions via magnetic resonance imaging (MRI) presents significant challenges.
- Histopathological validation of combined MRI sequence performance for cortical lesion detection in routine clinical settings is lacking.
Purpose of the Study:
- To determine the detection rate of histopathologically validated cortical lesions.
- To evaluate the combined performance of multiple MRI sequences in postmortem in situ imaging for multiple sclerosis (MS).
Main Methods:
- Five MRI sequences (PSIR, DIR, FLAIR, 3D-T₁, PD/T₂) were acquired at 3T in 18 postmortem MS brains.
- 66 tissue samples were histopathologically analyzed for myelin to identify cortical lesion types I-IV.
- Cortical lesions were assessed prospectively and retrospectively on MRI, blinded and unblinded to histopathology.
Main Results:
- Histopathology revealed 115 cortical lesions in 16/18 patients.
- Prospective assessment using combined MRI sequences detected 17.4% of lesions with 100% specificity.
- The combination of DIR and PSIR sequences improved detection by 43% compared to conventional sequences; retrospective assessment reached 40% detection.
Conclusions:
- Cortical lesion detection in MS using advanced MRI remains limited, even in controlled postmortem studies.
- The combination of DIR and PSIR sequences demonstrates superior performance over conventional MRI sequences.
- These findings establish a benchmark for MRI-based cortical lesion detection and highlight current technological limitations in identifying MS cortical pathology.
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