White matter microstructural alterations in obstructive sleep apnea assessed by time-dependent diffusion MRI

Diffusion-based neurofluid imaging indices, such as the DTI-ALPS method, are influenced by underlying white matter microstructure. This study aimed to examine associations between obstructive sleep apnea (OSA) severity and white matter microstructure using the difference in apparent diffusion coefficients between oscillating gradient spin-echo and pulsed gradient spin-echo sequences (ΔOGSE–PGSE), and to clarify the structural background influencing diffusion-based neurofluid imaging indices. Forty patients with OSA underwent overnight polysomnography and time-dependent diffusion MRI. ΔOGSE–PGSE was calculated from OGSE- and PGSE-derived apparent diffusion coefficients and normalized to MNI standard space. Atlas-based region-of-interest (ROI) analysis was performed. Associations between ΔOGSE–PGSE and polysomnographic indices, including the apnea–hypopnea index (AHI) and hypopnea index (HI), as well as neurofluid-related imaging metrics—relative choroid plexus volume (rCPV), relative white matter hyperintensity volume (rWMHV), and the ALPS index—were evaluated using linear mixed-effects models. Voxel-based and ternary plot analyses were also performed. ROI analysis demonstrated significant negative associations between ΔOGSE–PGSE and AHI across multiple regions, including white matter and subcortical structures. Exploratory analyses additionally identified associations involving HI and several cortical regions, including the insular and temporal cortices. Among neurofluid-related metrics, rCPV showed significant associations with ΔOGSE–PGSE, whereas no significant associations were observed for the ALPS index or rWMHV. Sensitivity analyses using ROI erosion and cluster-robust standard errors yielded consistent association patterns. ΔOGSE–PGSE demonstrated associations with white matter microstructural alterations related to OSA. These findings show that ΔOGSE–PGSE is sensitive to microstructural features not fully captured by conventional diffusion MRI. Although ΔOGSE–PGSE does not directly assess glymphatic function, it provides insight into shared microstructural features that form part of the structural background influencing diffusion-based neurofluid imaging indices, including ALPS, and supports their interpretation in obstructive sleep apnea.