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

新生儿缺氧缺血性脑病(HIE)是导致新生儿死亡和残疾的主要原因 在全世界范围内，临床表现为新生儿脑病，在 出生后短时间窗口通知神经保护干预措施。治疗性低温(TH) 在6小时内开始治疗中到重度HIE后，显著改善了预后 LIFE(HOL)，但试验不包括轻度HIE。辨别临床严重程度的困难 出生后不久对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研究的轻度HIE，神经生理学 和神经成像生物标记物是迫切需要的1)以指导实时患者选择在 短的治疗窗口和2)提供对代谢能量衰竭的时机的洞察和 对大脑结构和功能结果的影响。我们的团队率先提出了一种“小波神经血管 动态条件下测量神经血管偶联(NVC)的“束”分析系统 和实时，并进一步测量区域氧气消耗的核心 大脑能量动态平衡。父母助学金最初侧重于中到重度婴儿 在72小时的治疗期间，HIE出版了26本新的出版物。最重要的是 这次更新的目标是利用我们的新生理生物标记物来专注于未经治疗的轻度 他要找出需要治疗的人。我们的目标是测试动态生物标记物 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特有的生理和代谢障碍。我们计划招收一批新的 100例轻度新生儿缺氧缺血性脑病(3年内每年35例)，并对婴儿进行两年随访 发展成果。我们的基础设施确保了这项提议的成功，并包括 血流动力学和电生理信号方面的多学科专家团队(Chalak， 生物工程(Liu)和神经成像(Liu P，Wisnowski)。高成交量、支持性 Parkland医院的研究环境，包括位于医院内的3T西门子Skyra NICU，允许在新生儿出生的第一天就对患病的新生儿进行成像。新知识将会 具体提供：1)发展和优化神经成像和神经生理学 对轻度HIE的评估；2)通过多模式评估改善HIE分层。 冲击力。实时监测全球神经血管功能的能力可能导致一种范式 通过为视野提供敏感的生理生物标记物来检测缺陷的演变 在轻度HIE中，并允许在这一未研究的人群中进行有针对性的干预。吸引人的社区 利益攸关方确保国家卫生研究院的任务始终与受影响家庭的优先事项保持一致。

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.