Obstructive sleep apnea (OSA) is a common multisystem sleep disorder¹ and with the rise of people with obesity and older age, it has become a potentially disabling health problem^2,3. Continuous positive airway pressure (CPAP) is the most common treatment method for OSA patients. Several neuro-imaging studies mainly based on structural imaging have examined the impact of CPAP treatment on OSA patients^4-6. However, to date there are only a limited number of metabolite studies using 1D MRSI⁶. In this study, we examined neurochemical changes of untreated and CPAP treated OSA patients versus healthy controls in several brain regions to demonstrate neurochemical changes using an accelerated five-dimensional (5D) echo-planar J-resolved spectroscopic imaging (EP-JRESI)⁷ sequence and compressed sensing (CS) reconstruction. We hypothesized that metabolite integrity would be altered in untreated OSA patients and subsequently, abnormalities would be at least partially reversible after treatment with CPAP.We assessed seven untreated OSA patients (50.6±16.3years), seven OSA patients with minimum 3 months of CPAP (56.4±9.6years) and five healthy controls (HC) (43.4±15.6 years). All data were collected on a Siemens 3T Prisma MRI scanner using a 16 channel head receive coil. The following parameters were used for water-suppressed 5D EP-JRESI: TR/TE=1.2s/30ms, voxel resolution=1.5x1.5x1.5cm³, 64∆t₁ increments, 256 bipolar echo pair, FOV=24x24x12cm³, 1 average, non-uniform sampling (NUS)= 12.5% with a scan time≈20 min. A maximum echo sampling scheme was applied⁸ and after postprocessing⁸ bandwidth was ±250Hz along F1 and 1190Hz along F2. This was followed by a non water-suppressed scan with only the first t₁ increment. The undersampled data was reconstructed using a modified Split Bregman algorithm⁹ which solves the optimization problem, $$\min_{u} TV(u) \quad \text{s.t. } \|R\mathcal{F}u - f\|_2^2 < \sigma^2$$ where u is the reconstructed data, f is the undersampled data, $$$\sigma^2$$$ is an estimate of the noise variance, TV is the total variation norm, R is the NUS masking operator, and $$$\mathcal{F}$$$ is the Fourier transform operator. Before each EP-JRESI scan, 3D high resolution T1-weighted images for localization were collected using a MP-RAGE pulse sequence. Acquired data were post-processed with a custom MATLAB-based program and metabolite ratios with respect to the 3.0 ppm creatine (Cr) peak were calculated using peak integration. The metabolite differences between the three groups were tested with student’s t-test. Additionally, 5D EP-JRESI data were acquired from one HC and one OSA+CPAP in the same day (n=3) for a test-retest study.Figure 1(a) shows the PRESS VOI localization volume on a T1-weighted axial MRI of a 50-year-old OSAS patient brain. Representative 2D J-resolved spectra extracted from the mid-occipital and left insular cortex regions of the same subject following CS reconstruction are shown in Figure 1(b) and 1(c) respectively. Figure 2 and Fig. 3 show the selected metabolite ratios with respect to Cr in the frontal white/gray, occipital white/gray, left and right insular cortex and parietal insular cortex regions of the three groups: healthy controls, baseline OSA and OSA+CPAP respectively. Statistically significant differences were found between OSA patients and HC subjects in the occipital gray N-acetylaspartate(NAA)/Cr (1.43[0.13] vs 1.79[0.33]), frontal gray choline(Ch)/Cr (0.35[0.08] vs 0.45[0.07]), frontal gray myo-inositol(mI)/Cr (1.18[0.09] vs 1.36[0.05]), and occipital white Ch/Cr (0.24[0.06] vs 0.32[0.07]) ratios. When comparing OSA+CPAP with HC, significant differences in occipital gray NAA/Cr and frontal gray mI/Cr remained (Figure 2 and 3). NAA/Cr and Ch/Cr reduced further in the right insular cortex regions. Comparison between the baseline OSA and the OSA+CPAP patients showed significantly increased NAA/Cr, and Ch/Cr in the occipital white. The coefficient of variation(CV) of NAA, Ch, mI and Glx(glutamine+glutamate) ratios both in HC and OSA+CPAP for the test-retest study (n=3) were under 15% (Table 4).The results of the current study are in broad agreement with the previous 1D MRS studies^6,10,11. In general, we observed decreasing trends of NAA/Cr, Ch/Cr and Glx/Cr ratios in untreated OSA patients compared to HC. Most of the differences were seen to be reversed in the OSA+CPAP patients cohort. Reduced NAA/Cr ratio is indicative of impaired neuronal viability and/or integrity in those regions¹¹. Decreased Ch/Cr ratios may result from loss of myelin lipids or dysfunction of phospholipid metabolism¹⁰. Metabolite ratios were reproducible as demonstrated by small CV values for the two subjects in test-retest study.Studies using a large number of longitudinal subjects before and after CPAP are required to further validate the observations of the current study. Our findings are consistent with the known phenomenon of oxidative stress in OSA and reversibility of neurofunctional changes after CPAP. Nevertheless, accelerated 5D EP-JRESI can be used to monitor neurochemical changes in OSA patients and other brain pathologies.