Brain Changes in Pediatric Obstructive Sleep Apnea

小儿阻塞性睡眠呼吸暂停的大脑变化

• 批准号: 10218463
• 负责人: Rajesh Kumar
• 金额: $ 23.4万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-11 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10218463
• 关键词: Acute; Adenoidal structure; Adenoidectomy; Affect; Aftercare; Anti-Inflammatory Agents; Area; Arousal; Axon; Behavior; Behavioral; Brain; Brain Injuries; Breathing; Cerebellum; Cerebrovascular Circulation; Characteristics; Child; Child Behavior Checklist; Childhood; Chronic; Clinical Trials; Cognition; Cognitive; Contrast Media; Development; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Early Intervention; Emotions; Endothelial Cells; Evaluation; External Capsule; FDA approved; Fiber; Functional Magnetic Resonance Imaging; Functional disorder; Health; Hippocampus (Brain); Hypercapnia; Hypoxia; Image; Imaging Techniques; Impaired cognition; Injury; Insula of Reil; Internal Capsule; Intervention; Magnetic Resonance Imaging; Measures; Methods; Moods; Morbidity - disease rate; Myelin; Nature; Non-Steroidal Anti-Inflammatory Agents; Obstructive Sleep Apnea; Operative Surgical Procedures; Outcome; Pathologic; Patients; Performance; Perfusion; Pharmaceutical Preparations; Positron; Procedures; Process; Radial; Radiation; Recovery; Reproducibility; Risk; Schools; Site; Sleep; Sleep Fragmentations; Source; Spin Labels; Stroke; Symptoms; Syndrome; Thalamic structure; Tissues; Tonsil; Tonsillectomy; Traumatic Brain Injury; affective disturbance; airway obstruction; axon injury; base; blood oxygen level dependent; brain tissue; cognitive benefits; cognitive control; cognitive function; effective therapy; improved; neuroprotection; relating to nervous system; repaired; response; stem; tissue injury; water diffusion

PROJECT SUMMARY/ ABSTRACT Pediatric obstructive sleep apnea (OSA) is a common and progressive syndrome accompanied by severe cognition, mood, and daytime behavioral issues, as well as poor school performance, presumably stemming from compromised neural tissue, induced by intermittent hypoxia and perfusion changes. However, it is unclear whether the brain tissue injury is in acute or chronic condition, and whether myelin is preferentially affected than axons, an essential step to understand, since interventions for neural repair/recovery differ for acute vs chronic and myelin vs axonal injury. Also, it is unclear whether accompanying brain changes in pediatric OSA have functional consequences, resulting to cognitive or mood deficits. In addition, intermittent hypoxia triggers a cascade of injurious processes affecting endothelial cells, but unclear whether regional cerebral blood flow (CBF) is reduced in pediatric OSA. Treatment methods for pediatric OSA include tonsillectomy and/or adenoidectomy, and it is unclear whether brain tissue changes, regional CBF, and neural responses to cognitive challenge improve post-treatment. Using diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI)-based procedures, acute and chronic tissue changes and axonal status and myelin integrity can be assessed. Regional brain CBF can be assessed by validated arterial spin labeling (ASL) imaging, and regional neural activity to cognitive challenge can be examined with blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (MRI). Thus, using 28 treatment-naïve, pediatric OSA and 28 control children, the specific aims are to; determine the nature and types of brain tissue injury, using DTI and DKI measures, in untreated pediatric OSA over healthy controls; identify regional brain CBF, using ASL imaging, and neural responses to cognitive challenge, using BOLD functional MRI in pediatric OSA over healthy children; assess cognitive (by the differential ability scale II and NEPSY II) and emotion functions (by the child behavior checklist) in pediatric OSA compared to control children, and examine relationships between brain injury and cognitive and emotion dysfunctions in pediatric OSA; and examine whether brain tissue changes, reduced CBF, and altered neural responses to cognitive challenge reverse, and cognition and mood signs improve after adenotonsillectomy at 6 months in pediatric OSA. In summary, the nature and types of brain injury, regional CBF changes, and neural responses to cognitive challenge, and whether brain tissue changes, altered CBF, and diminished neural responses, as well as mood and cognitive functions recover after adenotonsillectomy in pediatric OSA will be examined. Evaluation of pathological characteristics is essential to assess the mechanisms of damage, and to suggest intervention strategies before and after surgery. The findings will also help guide potential treatments to rescue/restore brain tissue (e.g., nonsteroidal anti-inflammatory drugs) and improve CBF that could be implemented to benefit cognitive and mood health, and improve academic performance in pediatric OSA.

项目概要/摘要 小儿阻塞性睡眠呼吸暂停 (OSA) 是一种常见的进行性综合征，伴有严重的症状 认知、情绪和白天行为问题，以及学业表现不佳，可能是由于 间歇性缺氧和灌注变化引起的受损神经组织然而，尚不清楚。 脑组织损伤是急性还是慢性，髓磷脂是否优先受到影响 轴突，这是理解的一个重要步骤，因为神经修复/恢复的干预措施对于急性和慢性来说是不同的 此外，尚不清楚儿童 OSA 伴随的大脑变化是否有影响。 功能性后果，导致认知或情绪缺陷。此外，间歇性缺氧还会引发一系列症状。 影响内皮细胞的一系列损伤过程，但尚不清楚局部脑血流（CBF）是否 儿童 OSA 减少 儿童 OSA 的治疗方法包括扁桃体切除术和/或腺样体切除术， 目前尚不清楚脑组织、局部 CBF 和对认知挑战的神经反应是否发生变化 使用基于弥散张量成像 (DTI) 和弥散峰度成像 (DKI) 的方法改善治疗后效果。 可以评估急性和慢性组织变化以及轴突状态和髓磷脂完整性。 大脑 CBF 可以通过经过验证的动脉自旋标记 (ASL) 成像和区域神经活动来评估 认知挑战可以通过血氧水平依赖性（BOLD）功能磁共振检查 因此，使用 28 名未经治疗的儿童 OSA 和 28 名对照儿童，具体目标是： 使用 DTI 和 DKI 测量，确定未经治疗的儿童 OSA 的脑组织损伤的性质和类型 超过健康对照；使用 ASL 成像和认知神经反应来识别区域大脑 CBF 挑战，使用 BOLD 功能 MRI 评估儿科 OSA 与健康儿童的认知能力（通过差异化； 儿童 OSA 的能力量表 II 和 NEPSY II）和情绪功能（通过儿童行为检查表）进行比较 控制儿童，并检查脑损伤与认知和情绪功能障碍之间的关系 儿科 OSA；并检查脑组织是否发生变化、CBF 减少以及神经反应是否改变 腺样体扁桃体切除术后 6 个月，认知挑战逆转，认知和情绪体征有所改善 总之，脑损伤的性质和类型、局部 CBF 变化和神经反应。 认知挑战，以及脑组织是否发生变化、CBF 改变和神经反应减弱，如 将检查小儿 OSA 腺样体扁桃体切除术后情绪和认知功能的恢复情况。 病理特征的评估对于评估损伤机制至关重要，并提出建议 手术前后的干预策略也将有助于指导潜在的治疗方法。 挽救/恢复脑组织（例如非甾体类抗炎药）并改善 CBF 实施有利于儿童 OSA 的认知和情绪健康，并提高学业成绩。