Cerebral blood flow and neurocognition in children with obstructive sleep apnea

 描述（由申请人提供）：我是一名儿科睡眠医学初级研究员，接受过转化研究方面的高级培训。我的研究重点是阻塞性睡眠呼吸暂停综合征（OSAS）的病理生理学和并发症及其对神经系统功能的影响，包括感觉，认知和行为。OSAS很常见，影响2-3%的儿童。它与显著的发病率相关，如生长衰竭、全身性和肺动脉高压、内皮功能障碍、认知和行为缺陷。后者是至关重要的，因为大脑在童年时期经历了关键的发展，因此，认知和行为功能障碍的长期后果可能对儿童未来的成年生活产生重大影响。基于初步的数据，我们假设患有OSAS的儿童在觉醒和睡眠期间具有异常的脑血流（CBF）调节。我们进一步假设这种损害与行为和认知功能障碍的程度相关，并在OSAS治疗后得到改善。该提案包括一项机制研究，将评估CBF，脑氧饱和度，脑血容量测量的弥散光学光谱/弥散相关光谱与对照组相比，在觉醒和睡眠中的儿童OSAS，并将这些结果与一个全面的神经行为测试电池。OSAS患儿在扁桃体腺样体切除术后6个月和12个月进行复查，评估治疗后CBF、认知和行为的变化。对照组将在基线后6个月和12个月进行重新评估，以评估健康儿童随时间推移的CBF、认知和行为变化。这是一个最重要的研究领域，因为早期脑损伤与类似的后期损伤相比，导致发病风险增加。我全面的职业发展计划包括先进的生物统计学，光学物理学和光谱学，测量和评估以及临床试验设计的教学培训;以及儿科睡眠医学，神经病学，心理学和物理学领导者的指导。该计划将利用杰出的资源，如费城儿童医院研究所、临床转化研究奖、睡眠中心和神经血管成像实验室;以及宾夕法尼亚大学的漫射光学成像和光谱实验室。我的短期目标是：（1）将75%的精力投入到这项研究和培训计划中，（2）在该奖项的第4年提交基于这些发现的R 01提案。我的首要长期目标是成为一名独立的学术儿科医生-科学家，拥有NIH资助的临床转化研究计划，以调查儿科OSAS的病理生理学，未经治疗的OSAS的大脑后果以及治疗对发育中大脑的影响。其他目标是（1）指导下一代临床研究人员和培训补助金接受者，重点是少数民族研究人员和（2）参加西班牙裔倡导团体，以提高对服务不足人群的OSAS的认识。(End摘要）

 DESCRIPTION (provided by applicant): 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. (End of Abstract)