Abstract
Cortical multiple sclerosis lesions are disease-specific, yet inconspicuous on magnetic resonance images (MRI). Double inversion recovery (DIR) images are sensitive, but often unavailable in clinical routine and clinical trials. Artificially generated images can mitigate this issue, but lack histopathological validation. In this work, artificial DIR images were generated from postmortem 3D-T1 and proton-density (PD)/T2 or 3D-T1 and 3D fluid-inversion recovery (FLAIR) images, using a generative adversarial network. All sequences were scored for cortical lesions, blinded to histopathology. Subsequently, tissue samples were stained for proteolipid protein (myelin) and scored for cortical lesions type I-IV (leukocortical, intracortical, subpial and cortex-spanning, respectively). Histopathological scorings were then (unblinded) compared to MRI using linear mixed models. Images from 38 patients (26 female, mean age 64.3 ± 10.7) were included. A total of 142 cortical lesions were detected, predominantly subpial. Histopathology-blinded/unblinded sensitivity was 13.4/35.2% for artificial DIR generated from T1-PD/T2, 14.1/41.5% for artificial DIR from T1-FLAIR, 17.6/49.3% for conventional DIR and 10.6/34.5% for 3D-T1. When blinded to histopathology, there were no differences; with histopathological feedback at hand, conventional DIR and artificial DIR from T1-FLAIR outperformed the other sequences. Differences between histopathology-blinded/unblinded sensitivity could be minified through adjustment of the scoring criteria. In conclusion, artificial DIR images, particularly generated from T1-FLAIR could potentially substitute conventional DIR images when these are unavailable.
Highlights
Cortical multiple sclerosis lesions are disease-specific, yet inconspicuous on magnetic resonance images (MRI)
Cortical multiple sclerosis lesions are better discernible on double inversion recovery images, but these are often unavailable
With a combined postmortem in situ brain MRI and histopathology approach, we have found no differences in histopathology-blinded lesion detection between conventional Double inversion recovery (DIR) images and two variants of artificially generated DIR images
Summary
Cortical multiple sclerosis lesions are disease-specific, yet inconspicuous on magnetic resonance images (MRI). Cortical lesions are inconspicuous on MRI: histopathological sensitivity of conventional clinical sequences (i.e., T 1, T2, and fluid-attenuated inversion recovery (FLAIR)) lies beneath 10%6–8. They are not readily available in all hospitals and are omitted in most clinical trials This issue has recently been mitigated by the introduction of artificially generated DIR images[10,11]. Generated DIR images were found to detect an equal number of cortical lesions compared to conventionally acquired DIR images; histopathological validation is lacking to d ate[10,11]. The objective of the current work was to compare the sensitivity and specificity of artificially generated DIR images for cortical lesion detection in patients with multiple sclerosis, set against conventionally acquired DIR
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