Project Grant R01HL172928

TIME-RESOLVED MRI METHOD FOR EEG ASSISTED CONCURRENT MAPPING OF CEREBRAL OXYGEN METABOLISM AND AIRWAY STRUCTURE IN OBSTRUCTIVE SLEEP APNEA - PROJECT SUMMARY OBSTRUCTIVE SLEEP APNEA (OSA) IS THE MOST COMMON SLEEP DISORDER AND A RECOGNIZED RISK WITH AN ESTIMATED WORLDWIDE PREVALENCE OF ONE BILLION PEOPLE. THE ENSUING REPEATED EPISODES OF NOCTURNAL HYPOXIA AND HYPOXEMIA ARE AT THE CORE OF THE DISORDER'S PATHOGENESIS, LEADING TO UPREGULATION OF NEURO INFLAMMATION AND OXIDATIVE STRESS, WHICH PREDISPOSE OSA PATIENTS TO CARDIAC AND NEUROVASCULAR DISEASE ALONG WITH IMPAIRED COGNITIVE FUNCTION AND NEURODEGENERATION. THE INVESTIGATORS HAVE PREVIOUSLY EXAMINED THE NEUROVASCULAR-METABOLIC ALTERATIONS IN TERMS OF THE CEREBRAL METABOLIC RATE OF OXYGEN (CMRO2) AT REST AND IN RESPONSE TO APNEIC CHALLENGES DURING WAKEFULNESS IN THE FORM OF REPEATED CUED BREATH-HOLDS MIMICKING THE HYPERCAPNIC-HYPOXIC EVENTS OF SPONTANEOUS APNEA, BY MEANS OF TEMPORALLY-RESOLVED MRI-BASED BRAIN OXIMETRY. ALTHOUGH THIS WORK PROVIDED NEW INSIGHTS INTO CHRONIC AND ACUTE NEUROMETABOLIC CONSEQUENCES OF THE DISORDER, THE RESPONSE TO COACHED VOLITIONAL APNEAS LIKELY DIFFERS FROM THAT OF SPONTANEOUS APNEAS DURING SLEEP. ALSO UNKNOWN ARE THE UPPER AIRWAY'S MORPHOLOGIC CHANGES THAT OCCUR DURING APNEAS (FULL AIRWAY CLOSURE) AND HYPOPNEAS (PARTIAL CLOSURE) THAT CAUSE THE METABOLIC ALTERATIONS. LEADING UP TO THE PROPOSED PROJECT WE HAVE BEEN ABLE TO MONITOR CEREBRAL OXYGEN METABOLISM IN HEALTHY SUBJECTS IN THE SCANNER WITH CONCURRENT ELECTROENCEPHALOGRAPHY (EEG) AND DESIGNED AN IMAGING PROCEDURE THAT RETURNS THE VASCULAR-METABOLIC PARAMETERS AND UPPER AIRWAY MORPHOLOGY DURING CONTINUOUS SCANNING. WE ILLUSTRATE THE METHOD'S POTENTIAL WITH MODEL APNEAS INDUCED IN TEST SUBJECTS INVOLVING THE OROPHARYNGEAL PHASE OF SWALLOWING, CAUSING AIRWAY CLOSURE AND THE EXPECTED HYPOXIC-HYPERCAPNIC RESPONSE AND, MORE RECENTLY, IN A PATIENT WITH OSA DURING 90 MINUTES OF CONTINUOUS SCANNING AT SIX SECONDS TEMPORAL RESOLUTION DURING SLEEP IN THE SCANNER. THE KEY HYPOTHESIS UNDERLYING THE PROPOSED RESEARCH IS THAT THE METHOD CAN EVALUATE STATE-DEPENDENT O2 BRAIN METABOLISM AND AIRWAY ANATOMY IN OSA PATIENTS DURING WAKEFULNESS AND SLEEP AND DURING SPONTANEOUS APNEAS AND FURTHER, THAT THE ACUTE AIRWAY STRUCTURAL MANIFESTATIONS DURING APNEAS AND HYPOPNEAS CORRELATE WITH THE METABOLIC RESPONSE TO APNEAS. THE PROJECT COMPRISES THREE SPECIFIC AIMS: (1) OPTIMIZE THE TEMPORALLY RESOLVED INTERLEAVED STRUCTURAL AND METABOLIC MRI PROTOCOL AND SYNCHRONIZED AIRWAY PLETHYSMOGRAPHY TO CONFIRM THE METHOD'S ABILITY TO SIMULTANEOUSLY DETECT THE METABOLIC AND AIRWAY STRUCTURAL CHANGES DURING INDUCED APNEAS; (2) EXAMINE THE STATE DEPENDENCE OF O2 METABOLISM AND UPPER AIRWAY ANATOMY IN OSA PATIENTS DIFFERING IN DISEASE SEVERITY, WITH THE METHOD OF AIM 1 AND CONCURRENT EEG MONITORING; (3) EVALUATE THE HYPOTHESIS THAT THE TRANSIENT BRAIN METABOLIC AND UPPER AIRWAY CHANGES DURING APNEA CAN BE PREDICTED BY BASELINE MEASUREMENTS DURING RESPIRATION IN THE AWAKE STATE ALONG WITH THE SUBJECTS' BIOLOGICAL PROFILE OBTAINED FROM BLOOD MARKERS OF OXIDATIVE STRESS AND NEURO INFLAMMATION. THE PROPOSED RESEARCH SHOULD PROVIDE NEW INSIGHT INTO THE STRUCTURAL AND NEUROMETABOLIC IMPLICATIONS OF OSA AND THE DISORDER'S BIOLOGICAL UNDERPINNINGS, AND ULTIMATELY GUIDE THE DEVELOPMENT OF IMPROVED TREATMENT METHODS.