A Novel Wavelet Neurovascular Bundle for Real Time Detection of Injury in Neonatal Encephalopathy

用于实时检测新生儿脑病损伤的新型小波神经血管束

• 批准号: 10658773
• 负责人: LINA F CHALAK
• 金额: $ 63.19万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-15 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10658773
• 关键词: Acute; Affect; Alternative Therapies; Asphyxia; Biochemical; Biological; Biological Markers; Biomedical Engineering; Birth; Blood Vessels; Brain; Brain Injuries; Cessation of life; Circulation; Classification; Clinical; Cognitive; Coupling; Data; Detection; Development; Electroencephalography; Electrophysiology (science); Encephalopathies; Enrollment; Ensure; Environment; Evolution; Failure; Family; Funding; Future; Goals; Homeostasis; Hospitals; Hour; Image; Impairment; Individual; Infant; Infrastructure; Injury; Intervention; Knowledge; Life; Magnetic Resonance Imaging; Maps; Measures; Metabolic; Metabolism; Mission; Monitor; National Institute of Neurological Disorders and Stroke; Neonatal Mortality; Neurodevelopmental Impairment; Neurologic; Neurons; Newborn Infant; Outcome; Oxygen; Oxygen Consumption; Patient Selection; Perfusion; Phase; Physiological; Population; Predictive Value; Process; Public Health; Publications; Relaxation; Research; Research Personnel; Severities; Signal Transduction; Socioeconomic Factors; Spectrum Analysis; Stratification; Structure; Supportive care; Surrogate Endpoint; System; Testing; Therapeutic; Therapeutic Intervention; Time; Treatment Efficacy; United States National Institutes of Health; Vulnerable Populations; Work; brain health; clinical examination; cohort; community engagement; disability; disability risk; follow-up; functional outcomes; hemodynamics; improved; improved outcome; insight; metabolic rate; model design; multidisciplinary; multimodality; natural hypothermia; neonatal encephalopathy; neonatal hypoxic-ischemic brain injury; neonate; nervous system disorder; neurobiological mechanism; neuroimaging; neuroimaging marker; neurophysiology; neuroprotection; neurovascular; neurovascular coupling; novel; outcome prediction; parent grant; postnatal; predictive marker; predictive modeling; primary outcome; randomized trial; secondary outcome; success; targeted treatment

Hypoxic-ischemic encephalopathy (HIE) is the leading cause of newborn death and disability worldwide and presents clinically as neonatal encephalopathy that is difficult to classify within a short window after birth to inform neuroprotective interventions. Therapeutic hypothermia (TH) has dramatically improved outcomes in moderate to severe HIE when initiated within six hours of life (HOL), yet trials have not included mild HIE. The difficulties to discern the clinical severity shortly after birth and to analyze the dynamic circulation in sick newborns represent important challenges. As new trials are now considered to target unstudied mild HIE, neurophysiological and neuroimaging biomarkers are critically needed 1) to guide real-time patient selection within a short therapeutic window and 2) to provide insight into timing of the metabolic energy failure and effect on structural and functional brain outcomes. Our team pioneered a “wavelet neurovascular bundle” analytical system to measure neurovascular coupling (NVC) under dynamic conditions and in real time, and to measure regional oxygen consumption one step further into the core of brain energy homeostasis. The parent grant initially focused on infants with moderate to severe HIE during the 72 hours of treatment and resulted in twenty six new publications. The overarching goal of this renewal is to harness our novel physiological biomarkers to focus on untreated mild HIE to identify those who need treatment. Our objective is to test dynamic biomarkers that can predict structural and functional outcomes chosen with input from stakeholders, and inform physiological and metabolic disturbances specific to mild HIE. We plan to enroll a new cohort of 100 neonates with mild HIE (35 per year over 3 years) and to follow up for two years infants for developmental outcomes. Our infrastructure ensures the success of this proposal and includes a multidisciplinary team of experts in hemodynamics and electrophysiology signals (Chalak, Zhang), bioengineering (Liu), and neuroimaging (Liu P, Wisnowski). The high-volume, supportive research environment at Parkland Hospital, including a 3T Siemens Skyra located inside the NICU, permits imaging of sick newborns as early as the first day of life. New knowledge will specifically provide: 1) Development and optimization of neuroimaging and neurophysiological assessments of mild HIE; and 2) improved HIE stratification via multi-modal assessments. Impact. The ability to monitor global neurovascular functions in real time could lead to a paradigm shift by providing the field with sensitive physiological biomarkers to detect the evolution of deficits in mild HIE and allow targeted interventions in this unstudied population. Engaging community stakeholders ensures that the NIH mission remains aligned with the priorities of affected families.

缺氧缺血性脑病（HIE）是新生儿死亡和残疾的主要原因 在世界范围内，临床上表现为新生儿脑病，很难在一个类别中进行分类 出生后的短暂窗口期为神经保护干预提供信息。治疗性低温 (TH) 如果在 6 小时内开始治疗，可显着改善中度至重度 HIE 的结果 生命（HOL），但试验并未包括轻度 HIE。辨别临床严重程度的困难 出生后不久，分析患病新生儿的动态循环具有重要意义 挑战。由于新的试验现在被认为是针对未经研究的轻度 HIE，神经生理学 迫切需要神经影像生物标志物 1) 指导实时患者选择 治疗窗口短，2) 提供对代谢能量衰竭时间的深入了解和 对大脑结构和功能结果的影响。我们的团队首创了“小波神经血管 束”分析系统，用于测量动态条件下的神经血管耦合（NVC） 实时测量区域耗氧量，进一步深入核心 大脑能量稳态。家长补助金最初主要针对患有中度至重度婴儿 HIE 在 72 小时的治疗期间产生了 26 篇新出版物。首要的 此次更新的目标是利用我们的新型生理生物标志物来关注未经治疗的轻度 HIE 来识别那些需要治疗的人。我们的目标是测试动态生物标志物 预测根据利益相关者的意见选择的结构和功能结果，并告知 轻度 HIE 特有的生理和代谢紊乱。我们计划招收一批新的 100 名患有轻度 HIE 的新生儿（3 年内每年 35 名）并对两年内的婴儿进行随访 发展成果。我们的基础设施确保了该提案的成功，包括 血流动力学和电生理信号多学科专家团队（Chalak， 张）、生物工程（刘）和神经影像学（刘 P，Wisnowski）。流量大、支持性强 帕克兰医院的研究环境，包括位于医院内部的 3T 西门子 Skyra NICU 允许患病新生儿在出生第一天就进行成像。新知识将 具体提供： 1）神经影像学和神经生理学的开发和优化 轻度 HIE 的评估； 2) 通过多模式评估改进 HIE 分层。 影响。实时监测全球神经血管功能的能力可能会带来一个范例 通过为该领域提供敏感的生理生物标志物来检测缺陷的演变来实现转变 轻度 HIE，并允许对这一未经研究的人群进行有针对性的干预。参与社区 利益相关者确保 NIH 的使命与受影响家庭的优先事项保持一致。