Evaluating the T1w/FLAIR ratio as a proxy for myelin: Associations with myelin water Imaging, diffusion metrics, and cognition

PURPOSE: Although the T1w/T2w ratio was introduced as a proxy for myelin, it may reflect broader aspects of brain tissue health. The recently introduced T1w/FLAIR ratio has yet to be evaluated in relation to biological and clinical markers. This study investigates its association with myelin water fraction (MWF), diffusion MRI (dMRI), and cognitive performance, and explores whether alternative weightings of the ratio improve these associations. METHODS: 36 women were retrospectively included from a previous study with neuropsychological testing and 3T MRI. Spearman correlations assessed associations between the T1w/FLAIR ratio and MWF, fractional anisotropy (FA), mean diffusivity (MD), neurite density index (NDI), orientation dispersion index (ODI), and fraction of isotropic diffusion compartment (FISO). Region-specific and overall correlations were evaluated across 36 white matter regions, lesions, total white matter, and cortical and deep gray matter. Associations with attention, memory, and processing speed were examined. Least squares regression was used to derive an optimally weighted ratio based on MWF, and analyses were repeated using this weighted ratio. RESULTS: Significant correlations between the T1w/FLAIR ratio and MWF and/or dMRI measures were found in six out of 40 regions. Across regions and subjects, the ratio showed weak overall correlations (r < 0.5) with MWF, FA, NDI, and FISO. A significant positive correlation with memory was only observed within lesions. The optimal weighting favored a stronger contribution from the T1w signal but resulted in only slightly stronger correlations. CONCLUSION: Our results support the interpretation of T1w/FLAIR ratio as a general marker of tissue health rather than a specific measure for myelin.