The impact of intensity variations in T1-hypointense lesions on clinical correlations in multiple sclerosis

Background: The correlations between T1-hypointense lesion (‘black hole’) volume and clinical measures have varied widely across previous studies. The degree of hypointensity in black holes is associated with the severity of tissue damage, but the impact on the correlation with disability is unknown. Objectives: To determine how variations in the intensity level used for lesion classification can impact clinical correlation, specifically with the Expanded Disability Status Scale (EDSS), and whether using a restricted range can improve correlation. Methods: A highly automated image analysis procedure was applied to the scans of 24 multiple sclerosis (MS) patients with well-distributed EDSS scores to compute their black hole volumes at nine different levels of intensity relative to the reference intensities sampled in normal-appearing white matter (NAWM) and cerebrospinal fluid (CSF). Two methods of volume computation were used. Results: The black hole volume–EDSS Spearman correlations ranged between 0.49–0.73 (first method) and 0.54–0.74 (second method). The strongest correlations were observed by only including the voxels with maximum intensities at 30–40% of the CSF to NAWM range. Conclusions: Intensity variations can have a large impact on black hole–EDSS correlation. Restricting the measurement to a subset of the darkest voxels may yield stronger correlations.