The overall objectives of this research are 1) to characterize upper airway dynamics during wakefulness and sleep in patients with obstructive sleep apnea (OSA) using magnetic resonance imaging (MRI) and 2) to determine if data collected during wakefulness can predict the occurrence of OSA. OSA is characterized by recurrent partial or complete airway closure during sleep, and has important clinical implications ranging from disruption of sleep with daytime sequelae of excessive sleepiness and poor quality of life to adverse cardiovascular or metabolic outcomes. While polysomnography and studies based on measurements of airway pressures and resistance have provided a wealth of information on upper airway physiology, they are unable to assess the three-dimensional anatomy of the upper airway and its conformational changes during breathing. Knowledge of the morphology and mechanical behavior of this structure is essential for a more complete understanding of the occurrence of upper airway obstruction. Such information can be obtained with imaging technology and is the focus of this study. We propose to use state-of-the-art MRI tools to quantify upper airway dynamics in three groups of subjects: 1) OSA patients;2) snoring volunteers;and 3) healthy age and weight-matched controls for comparison purposes. Subjects will undergo MR imaging to assess upper airway morphometry and changes in airway size during tidal breathing both during wakefulness and natural sleep with simultaneous measurement of nasal-oral flow partition and sleep state and stages. Dynamic patient-specific models of upper airway morphometry will be reconstructed from the MR images from which various anatomical markers will be calculated. Differences in these markers between groups and between stages (awake vs. asleep) will be evaluated. The proposed studies of characterizing the conformational change of the upper airway during tidal breathing will provide a new means of identifying geometrical abnormalities that lead to airflow obstruction. This proposal is a first step in addressing a currently unmet clinical need for treatment guidelines tha take into account the dynamic nature of the upper airway. Completion of these studies will also lay the groundwork for future modeling studies that will combine patient-specific upper airway dynamics with detailed flow simulations to provide better insight in biomechanical properties of the upper airway and flow-driven mechanisms on which to optimize therapeutic treatment. The methods developed in this research will be directly applicable to all patient populations with upper airway dysfunction.

Public Health Relevance

The overall objectives of this research are 1) to characterize upper airway dynamics during wakefulness and sleep in patients with obstructive sleep apnea (OSA) using magnetic resonance imaging (MRI) and 2) to determine if data collected during wakefulness can predict the occurrence of OSA. Using MR images acquired in OSA patients, snorers and healthy controls, we will develop dynamic subject-specific models of upper airway morphometry in which various anatomical markers will be calculated and compared between groups and state (awake vs. asleep). The proposed research is relevant to public health as it will 1) provide a new means of identifying geometrical that lead to airflow obstruction, 2) provide important inputs into treatment planning of upper airway disorders allowing for the identification of patients that may benefit from surgical intervention, and 3) be applicable to the characterization of flow in patients with other upper airway disorder in future studies.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21HL121794-01A1
Application #
8771245
Study Section
Respiratory Integrative Biology and Translational Research Study Section (RIBT)
Program Officer
Twery, Michael
Project Start
2014-09-01
Project End
2016-06-30
Budget Start
2014-09-01
Budget End
2015-06-30
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Fiallo, Luis; Malhotra, Atul; LaBuzetta, Jamie Nicole (2016) A primer of neurologic emergencies: summary from the American Thoracic Society Meeting 2016. J Thorac Dis 8:S576-8
Deacon, Naomi; Malhotra, Atul (2016) Potential protective mechanism of arousal in obstructive sleep apnea. J Thorac Dis 8:S545-6
Hepokoski, Mark; Owens, Robert L; Malhotra, Atul et al. (2016) Mechanical ventilation in acute respiratory distress syndrome at ATS 2016: the search for a patient-specific strategy. J Thorac Dis 8:S550-2
Mbanze, Irina; Moschovis, Peter P; Malhotra, Atul (2016) The American Thoracic Society Global Scholars Program. J Thorac Dis 8:S586-7
Lam, Michael T Y; Grandner, Michael A; Malhotra, Atul (2016) Lungs can tell time-a highlight from 2016 ATS session on clock genes, inflammation, immunology, and sleep. J Thorac Dis 8:S579-81
Anderson, Ryan J; Malhotra, Atul; Kim, Nick H (2016) Pulmonary hypertension: evolution of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. J Thorac Dis 8:S562-5
Malhotra, Atul; Liang, Ni-Cheng (2016) Introduction: American Thoracic Society International Meeting 2016. J Thorac Dis 8:S528-9
Jaiswal, Stuti J; Malhotra, Atul; Owens, Robert L (2016) Sleep and critical illness: bridging the two pillars at the ATS 2016. J Thorac Dis 8:S536-8
Malhotra, Atul; Jordan, Amy (2016) The importance of arousal in obstructive sleep apnea-updates from the American Thoracic Society 2016. J Thorac Dis 8:S542-4
Li, Yanru; Owens, Robert L; Sands, Scott et al. (2016) The Effect of Donepezil on Arousal Threshold and Apnea-Hypopnea Index. A Randomized, Double-Blind, Cross-Over Study. Ann Am Thorac Soc 13:2012-2018

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