I am a junior investigator in pediatric sleep medicine with advanced training in translational research. My research is focused on the pathophysiology and complications of the obstructive sleep apnea syndrome (OSAS) and their influence on nervous system function, including sensation, cognition and behavior. OSAS is common, affecting 2-3% of children. It is associated with significant morbidity such as growth failure, systemic, and pulmonary hypertension, endothelial dysfunction, cognitive and behavioral deficits. The latter is of paramount importance as the brain undergoes crucial development during childhood and thus, the long-term consequences of cognitive and behavioral dysfunction may have great impact on children's future adult life. Based on preliminary data, we hypothesize that children with OSAS have abnormal cerebral flood flow (CBF) regulation during wakefulness and sleep. We further hypothesize that this impairment correlates with the degree of behavioral and cognitive dysfunction, and improves after treatment of OSAS. This proposal comprises a mechanistic research study that will evaluate CBF, cerebral oxygen saturation, and cerebral blood volume measured by diffuse optical spectroscopy/diffuses correlation spectroscopy during wakefulness and sleep in children with OSAS compared with controls, and correlate these findings with a comprehensive neurobehavioral testing battery. Children with OSAS will be retested 6 and 12 months after adenotonsillectomy evaluate CBF, cognitive and behavioral changes after treatment. Controls will be reevaluated 6 and 12 months after baseline to assess CBF, cognitive and behavioral changes over time in the healthy children. This is a most significant area of research as early brain insults result in increased risk of morbidity compared with similar later insults. My comprehensive career development plan includes didactic training in advanced Biostatistics, Optical Physics and Spectroscopy, Measurement and Assessment, and Clinical Trial Design; and mentorship by leaders in pediatric sleep medicine, neurology, psychology, and physics. This plan will draw on outstanding resources, such as the Children's Hospital of Philadelphia Research Institute, Clinical Translational Research Award, Sleep Center, and Neurovascular Imaging Laboratory; in addition to the Diffuse Optical Imaging and Spectroscopy Laboratory at the University of Pennsylvania. My short term goals are to: (1) dedicate 75% effort to this research and training program and (2) to submit an R01 proposal based on these findings by year 4 of this award. My overarching long-term goal is to become an independent and established academic pediatric physician-scientist with an established NIH-funded clinical translational research program to investigate the pathophysiology of pediatric OSAS, the brain consequences of untreated OSAS, and the impact of treatment on the developing brain. Additional goals are to (1) mentor the next generation of clinical investigators and training-grant recipient with an emphasis on minority researchers and (2) participate in Hispanic advocacy groups to raise awareness of OSAS in underserved populations.
This project aims to understand the mechanisms of cognitive and behavioral dysfunction in children with the obstructive sleep apnea syndrome (OSAS). The project will use a novel non- invasive optical device to measure cerebral blood flow and other determinants of brain metabolism during wakefulness and sleep in children with OSAS and controls. These measurements will be correlated with neurobehavioral testing results.