White matter alterations in episodic migraine without aura patients assessed with diffusion MRI: effect of free water correction

Objective: To assess the effect of modeling free water (FW) on the identification of white matter (WM) microstructure alterations using diffusion Magnetic Resonance Imaging (dMRI) in episodic migraine without aura patients compared with healthy controls. Background: Diffusion tensor imaging (DTI) studies examining WM in migraine patients previously overlooked the potential influence of FW partial volume effects. Correcting FW effects could offer a clearer understanding of WM changes in migraine. This study is the first to incorporate FW effects when evaluating alterations in WM tracts in migraine patients, offering a comparison to standard DTI analysis. Methods: A group of 14 patients with low-frequency episodic menstrual-related migraine without aura and 15 healthy controls matched for the phase of the menstrual cycle were recruited and underwent dMRI acquisitions. FW partial volume fraction was estimated, the diffusion signal corrected and the diffusion parameters calculated from both FW-corrected and uncorrected signals. Tract-Based Spatial Statistics (TBSS) and WM skeleton regions of interest (ROI) analyses were used to compare between groups. Results: Comparisons between control subjects and migraine patients with TBSS and ROI analyses revealed significantly lower axial diffusivity (AD), both with and without FW correction, as well as altered FW values in migraine patients in some WM tracts. TBSS detected MD changes only after FW correction. Conclusions: These findings suggest WM alterations in these migraine patients in comparison with control subjects, in accordance with other migraine studies. Differences in the diffusion parameters might point to inflammatory processes in migraine related to cellular swelling.