Towards quantitative intensity analysis of conventional T1-weighted images in multiple sclerosis

Conventional T1-weighted (T1w) magnetic resonance imaging (MRI) is commonly used in multiple sclerosis (MS) morphometry and volumetry research. However, arbitrary intensity scales preclude interpretation of signal values across patients, sites, and time. This requires quantitative MRI techniques, which are not always available. This study assessed T1w image intensity scaling methods, relying on extracerebral reference regions, for quantitative analysis of brain MRI in MS. In total, 701 people with a diagnosis of radiologically isolated syndrome, clinically isolated syndrome, or MS were included. Four intensity scaling strategies were applied: 1) MRI signal modeling, 2) linear scaling with reference regions, 3) z-score standardization, and 4) none (only bias field correction). Methods were evaluated using variance analysis, R1 map comparison, and normal-appearing white matter (NAWM) intensity group comparison, using mean and coefficient of variation (CoV), between low (≤3) and high (>3) expanded disability status scale (EDSS) scores. Statistical analysis was conducted using Pearson's r, two-sided Welch two-sample t-test, ANCOVA, and Cohen's d. Linear scaling with temporal fatty tissue achieved the most consistent variance reduction and strong correlation with R1 maps (r = 0.84). R1 values in NAWM were significantly lower in people with high compared to low EDSS scores (d = -0.351). Similarly, group differences in mean NAWM intensity of fat-scaled images were significant (d = -0.252). The largest group differences were found in NAWM CoV in bias field-corrected T1w images (d = 0.818). Linear scaling with fatty tissue most accurately reproduced the results obtained with R1 maps. Changes in MS NAWM appear to increase intensity variability detectable in conventional T1w images.