T1W/T2W Ratio to Assess Brain Microstructural Damage in Multiple Sclerosis: A Multicenter Study.

BACKGROUND AND PURPOSE: The T1-weighted/T2-weighted ratio, a proposed surrogate measure of myelin integrity/damage, has debated specificity in multiple sclerosis. We investigated compartment-specific T1-weighted/T2-weighted alterations across multiple sclerosis phenotypes and age at onset, and their associations with disability and cognition.

MATERIALS AND

METHODS

In this multicenter study, 918 multiple sclerosis and 272 healthy controls from an Italian neuroimaging initiative underwent standardized 3D T1- and T2-weighted MRI (3D or 2D dual-echo sequences depending on site), together with clinical and cognitive assessments. T1-weighted/T2-weighted ratios were computed using a standardized pipeline and multiple sclerosis z-scores were derived across brain regions using linear mixed-effects models fitted on healthy controls. Associations with disease duration, disability, and Symbol Digit Modalities Test were analyzed.

RESULTS

Compared with healthy controls, patients showed lower T1-weighted/T2-weighted ratios in lesions, normal-appearing white matter, and cortical grey matter (all FDR-adjusted p-values<.001), and higher ratios in the thalamus and deep grey matter (all FDR-adjusted p-values≤.01). Differences were more pronounced in secondary progressive and relapsing-remitting multiple sclerosis (all FDR-adjusted p-values<.001) than clinically isolated syndrome and primary progressive. Pediatric-onset patients showed lower normal-appearing white matter and cortical grey matter ratios (all FDR-adjusted p-values≤.02) than adult- and late-onset patients, which conversely showed higher deep grey matter ratios compared to the other groups (all FDR-adjusted p-values≤.01). Higher disability was associated to lower lesion, normal-appearing white matter, cortical grey matter ratios (all p≤.05) and higher thalamic ratios (p=.006). Longer disease duration correlated with lower lesion (p=.02), normal-appearing white matter ratios (p=.007) and higher deep grey matter ratios (p=.002). Worse cognitive performance was associated with lower cortical (p=.01), and higher thalamic and deep grey matter ratios (all p≤.004).

CONCLUSIONS

T1-weighted/T2-weighted mapping can provide complementary, compartment-specific information on tissue integrity and clinical outcomes across the MS spectrum.