Improving understanding of sleep apnea pathogenesis using novel imaging techniques during sleep

About This Grant

ABSTRACT OSA is a chronic condition characterized by recurrent complete (apnea) or partial (hypopnea) airway collapse during sleep. Effective and long-term treatment is required to reduce the large public health burden associated with OSA. A better characterization of the site and pattern of airway collapse and how upper airway anatomy mediates this collapse would provide new insights into OSA pathogenesis and can guide optimal therapies, particularly for the 30-50% of patients who cannot tolerate positive airway pressure (PAP) therapy (the first-line treatment). Currently, our knowledge of the upper airway anatomy that increases risk for developing OSA is largely based on magnetic resonance imaging (MRI) or computed tomography (CT) studies during wake. However, visualizing the upper airway during sleep (concurrent with apneas) would allow us to develop more mechanistic insights into how and why the upper airway narrows or collapses. One way to achieve this is through drug-induced sleep endoscopy (DISE), a clinical procedure that simulates sleep with propofol. By examining pressure-flow and pressure-area relationships during DISE, we are able to quantify the pressure required to open (pharyngeal opening pressure [PhOP]) or close (critical closing pressure [Pcrit]) the airway and obtain key insights into the pattern (anterior-posterior or lateral) and location (retropalatal or retroglossal region) of airway collapse. While our approach to DISE is state-of-the-art, it is not able to visualize the movements by which pharyngeal soft tissues and craniofacial structures mediate airway closure. However, dynamic MRI during sleep can provide high resolution imaging of upper airway anatomy across multiple sleep stages and apneas. The global hypothesis of this R01 is that the combination of state-dependent MRI and novel phenotyping from DISE will provide new insights into the mechanisms of upper airway collapse during apneas by identifying the anatomic structures that mediate segmental airway collapse and providing key information on regional airway compliance and closing pressures. Aim 1 will use state-dependent MRI to determine (1A) the site, pattern and magnitude of airway collapse during sleep, (1B) the anatomical movements that mediate retropalatal and retroglossal airway collapse, and (1C) whether these pharyngeal changes differ by sleep stage. Aim 2 will use novel methods during DISE to (2A) objectively quantify airway collapse, (2B) perform pressure-area analysis to measure regional compliance of specific pharyngeal segments, and (2C) use pressure-flow relationships to quantify PhOP and Pcrit. Aim 3 will combine data in Aims 1 and 2 to examine the mechanisms of airway collapse during sleep, including if characteristics of collapse on DISE and MRI agree and how compliance and pressure-flow relationships on DISE differ based on the MRI sleep-related movement of pharyngeal structures. Aim 4 will explore the ability to predict successful response to clinically-indicated upper airway surgery for OSA using these imaging modalities. Overall, this project utilizes a multidisciplinary approach to elucidate state-dependent mechanisms of upper airway collapse by linking anatomic changes with alterations in airflow dynamics.