Obstructive sleep apnea (OSA), a condition characterized by persistent events of partial/complete upper airway obstruction, with continued diaphragmatic efforts during sleep, shows gray matter injury principally located in autonomic, respiratory, mood, and cognitive control sites, as observed with various MRI techniques.^1,2 Regional gray matter changes can be accompanied by subcortical and white matter myelin integrity loss in the condition; yet, the extent of myelin changes in OSA is unclear. Myelin integrity can be assessed with T2-relaxometry, radial diffusivity, and magnetization transfer imaging; however, these procedures require special image processing skills, have poor resolution, and determination is time consuming. Previous studies suggest that myelin integrity of subcortical and white matter areas varies with both T1-weighted and T2-weighted signal intensities, but in opposite directions,³ and the ratio of these two weighted images can indicate regional subcortical and white matter myelin changes. Thus, this ratio procedure of T1-weighted and T2-weighted images, a method that is simple, requires little time, and provides higher resolution data, can be used to examine myelin integrity in OSA subjects.^4,5 Our aim was to examine regional subcortical and white matter myelin integrity in recently-diagnosed, treatment-naive OSA vs. control subjects using T1- and T2-weighted images. We hypothesized that regional myelin integrity will be decreased in OSA over controls, and that these changes will appear in autonomic, respiratory, cognitive, and mood regulatory regions.Mathematically, the ratio of T1-weighted/T2-weighted images could be modeled as $$$\frac{T1-weighted}{T2-weighted} ≈ \frac{α1*x}{α2*\frac{1}{x}} = \frac{α1}{α2}x^{2} = βx^{2}$$$, where myelin integrity is represented by x. Thus, by calculating the ratio of two weighted images, myelin contrast will be improved significantly. The variables α1, α2 are scaling factors related to bias field inhomogeneties.⁶We studied 56 OSA (age, 48.5±8.6 years; body-mass-index, 31.1±6.1 kg/m²; 42 male; apnea-hypopnea-index (AHI), 35.9±22.9 events/hour) and 91 control subjects (age, 46.7±9.0 years; body-mass-index, 24.8±3.5 kg/m²; 56 male). All OSA subjects were recently diagnosed via an overnight polysomnography with at least moderate severity (AHI ≥ 15). Control subjects were healthy, without any medications that might alter brain tissue. Brain imaging studies were performed using a 3.0-Tesla MRI scanner (Magnetom Tim-Trio; Siemens). High-resolution T1-weighted images were acquired using a MPRAGE pulse sequence (TR=2200 ms; TE=2.2 ms; inversion-time=900 ms; flip-angle (FA)=9°; matrix-size=256×256; FOV=230×230 mm; slice-thickness=1.0 mm). T2-weighted images were collected using a spin-echo pulse sequence in the axial plane (TR=10,000 ms; TE=134 ms; FA=1300; matrix size=256×256; FOV=230×230 mm; slice-thickness=3.5 mm). Both T1-weighted and T2-weighted images were bias-corrected, T2-weighted images were co-registered to their corresponding T1-weighted images, and myelin maps were computed by dividing the T1-weighted images with the resliced T2-weighted images (Fig. 1A). We normalized the ratio maps to Montreal Neurological Institute (MNI) space, and smoothed (Gaussian kernel, 10 mm). High-resolution T1-weighted images of a control subject were normalized to MNI space, to create background images. The smoothed myelin maps were compared between groups using ANCOVA (covariates: sex, age; SPM12, family-wise-error (FWE) corrected p<0.05, cluster-size 20 voxels). Brain clusters with significant differences between groups were overlaid onto background images for structural identification.No significant differences in age (p=0.23) or gender (p=0.10) appeared between groups. However, body-mass-indices were significantly higher in OSA (p<0.0001). Multiple brain areas in OSA showed decreased myelin integrity, compared to control subjects (Fig. 1B, p <0.05, FWE corrected). Brain sites in OSA that showed decreased myelin integrity included the bilateral insular, temporal, parietal and occipital cortices (Fig. 1Ba,b,c), right orbital frontal cortex and white matter (Fig. 1Be), anterior and posterior cingulate cortex and cingulum bundle, extending to the genu of the corpus callosum and prefrontal sites (Fig. 1Bf), cerebellar peduncles (Fig. 1Bg), basal forebrain (Fig. 1Be), right hippocampus, and amygdala (Fig. 1Bc). Other brain areas with decreased myelin integrity appeared in the caudate nuclei, extending to the internal and external capsules (Fig. 1Bb), cerebellar vermis (Fig. 1Bg), frontal and parietal white matter (Fig. 1Bj,1Bf), and right ventral medulla (Fig. 1Bd).Regional brain myelin integrity is significantly decreased in multiple sites in OSA over controls. These regions with changes are principally localized in critical autonomic, cognitive, memory, respiratory, and affective control sites, including the frontal, temporal, parietal, cingulate and insular cortices, hippocampus, cerebellar peduncles, and ventral medulla, and may result from hypoxic/ischemic processes in the condition. The findings indicate that myelin mapping, based on the ratio of T1- and T2-weighted images, can be used to assess regional myelin alterations.