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

缺氧缺血性脑病（Hypoxic-ischemic encephalopathy，HIE）是新生儿死亡和致残的主要原因 在临床上表现为新生儿脑病，难以归类为 出生后的短窗口，告知神经保护干预措施。治疗性低温 当在6小时内开始治疗时， 生活（HOL），但试验不包括轻度HIE。识别临床严重程度的困难 对新生儿出生后不久进行动态循环监测和分析具有重要意义 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 和神经影像学生物标志物是迫切需要的1）指导实时患者选择内， 短的治疗窗口和2）提供对代谢能量衰竭的时间的洞察， 对大脑结构和功能的影响。我们的团队开创了“小波神经血管 束”分析系统，以测量动态条件下的神经血管耦合（NVC 和真实的时间，并测量区域耗氧量的核心进一步， 大脑能量平衡父母补助金最初集中在中度至重度 在治疗的72小时内发生HIE，并导致26篇新的出版物。总体 这次更新的目标是利用我们新的生理生物标志物来关注未经治疗的轻度 以确定那些需要治疗的人。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输入选择的结构和功能成果，并告知 轻度HIE特有的生理和代谢紊乱。我们计划招募一批新的 100例轻度HIE新生儿（3年内每年35例），随访2年， 发展成果。我们的基础设施确保了这一建议的成功，包括 血液动力学和电生理信号的多学科专家小组（Chalak， Zhang）、生物工程（Liu）和神经成像（Liu P，Wisnowski）。高容量，支持性 帕克兰医院的研究环境，包括位于 新生儿重症监护室，允许成像生病的新生儿早在生命的第一天。新知识将 具体提供：1）开发和优化神经影像学和神经生理学 轻度HIE的评估;和2）通过多模式评估改善HIE分层。 冲击在真实的时间内监测整体神经血管功能的能力可能会导致一个范例 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 在轻度HIE和允许有针对性的干预措施，在这个未经研究的人口。邀请社区 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。

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.