Neurochemical Assessment of Sleep Apnea using Accelerated MR Spectroscopic Imaging

University Of California Los Angeles, Los Angeles CA

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Abstract

Obstructive sleep apnea (OSA) is a common sleep disorder characterized by repeated apneic episodes. It is accompanied by cognitive, motor, autonomic, and affective abnormalities. Multiple brain sites are involved in the regulation of these symptoms, especially autonomic and neuropsychological behaviors. One-dimensional (1D) MR Spectroscopy (MRS) combined with two- or three-dimensional (2D/3D) spatial encoding is referred to as MR Spectroscopic Imaging (MRSI), and has the potential to noninvasively measure critical metabolites and neurochemical changes in vivo across multiple regions in patients suffering from OSA; however, existing measures provide limited understanding of the underlying causes of sleep disorder pathologies. Our group recently implemented novel four-dimensional (4D) multi-voxel-based 2D MRS sequences, including echo planar J-resolved spectroscopic imaging (EP-JRESI), to record multiple 2D J-resolved spectra. This offers improved spectral resolution relative to 1D MRS from a slice with a total acquisition duration of approximately 30 minutes. A five-dimensional (5D) EP-JRESI requires several hours of acquisition. It is feasible to enhance the speed of MRI/MRSI using non-uniform undersampling (NUS) along selected spatial and spectral dimensions, and compressed sensing (CS) based reconstruction. Three specific aims of this application are: 1) Record MR spectra in multiple brain regions of OSA subjects and healthy controls using a recently implemented 5D EP-JRESI NUS sequence on a 3T Prisma MRI scanner. 2) Calculate markers of injury including mean diffusivity (MD) and fractional anisotrophy (FA) from diffusion tensor imaging (DTI), and 3D MP-RAGE for mapping white and gray matter and CSF fractions in OSA patients and healthy subjects. 3) Perform the Montreal Cognitive Assessment (MoCA) to assess cognition, and correlate the multi-voxel-based 2D MRS, DTI and MP-RAGE data acquired in OSA and healthy subjects with MoCA test scores and OSA severity indices. The following hypotheses will be tested: 1) Compared to the mild OSA controls and healthy subjects, severe OSA subjects will demonstrate significant metabolite changes in multiple brain regions including frontal, insular and occipital cortices, thalamus and hippocampi regions responsible for hypoxia and inflammation related injury. 2) MP-RAGE analysis will allow identification of gray/white matter and CSF boundaries to combine with quantitation of cerebral metabolites. Diffuse reduction of WM fiber integrity will be reflected by DTI metric changes in multiple brain areas. 3) Metabolite ratios derived from multi-dimensional MRS results will be associated with DTI metrics (MD and FA), and cognition changes evaluated by MoCA and OSA severity, allowing determination of region-specific neurochemical and anatomical biomarkers in OSA. Novel elements include neurochemical characterization of OSA in multiple brain locations with novel biomarkers , and cognition assessment related to neurochemical and structural markers of injury.