Feasibility of detecting atrophy relevant for disability and cognition in multiple sclerosis using 3D-FLAIR

Background and objectives: Disability and cognitive impairment are known to be related to brain atrophy in multiple sclerosis (MS), but 3D-T1 imaging required for brain volumetrics is often unavailable in clinical protocols, unlike 3D-FLAIR. Here our aim was to investigate whether brain volumes derived from 3D-FLAIR images result in similar associations with disability and cognition in MS as do those derived from 3D-T1 images. Methods: 3T-MRI scans of 329 MS patients and 76 healthy controls were included in this cross-sectional study. Brain volumes were derived using FreeSurfer on 3D-T1 and compared with brain volumes derived with SynthSeg and SAMSEG on 3D-FLAIR. Relative agreement was evaluated by calculating the intraclass correlation coefficient (ICC) of the 3D-T1 and 3D-FLAIR volumes. Consistency of relations with disability and average cognition was assessed using linear regression, while correcting for age and sex. The findings were corroborated in an independent validation cohort of 125 MS patients. Results: The ICC between volume measured with FreeSurfer and those measured on 3D-FLAIR for brain, ventricle, cortex, total deep gray matter and thalamus was above 0.74 for SAMSEG and above 0.91 for SynthSeg. Worse disability and lower average cognition were similarly associated with brain (adj. R² = 0.24–0.27, p < 0.01; adj. R² = 0.26–0.29, p < 0.001) ventricle (adj. R² = 0.27–0.28, p < 0.001; adj. R² = 0.19–0.20, p < 0.001) and deep gray matter volumes (adj. R² = 0.24–0.28, p < 0.001; adj. R² = 0.27–0.28, p < 0.001) determined with all methods, except for cortical volumes derived from 3D-FLAIR. Discussion: In this cross-sectional study, brain volumes derived from 3D-FLAIR and 3D-T1 show similar relationships to disability and cognitive dysfunction in MS, highlighting the potential of these techniques in clinical datasets.