Perinatal Brain Injury: Potential of Innovative NIRS to Optimize Hypothermia

围产期脑损伤：创新 NIRS 优化低温治疗的潜力

• 批准号: 9093827
• 负责人: Patricia Ellen Grant
• 金额: $ 71.11万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9093827
• 关键词: Accounting; Acute; Affect; Age; Anisotropy; Behavioral; Blood; Brain Hypoxia-Ischemia; Brain Injuries; Cell Death; Cerebrovascular Circulation; Cerebrum; Cognitive; Control Groups; Detection; Devices; Diffuse; Diffusion; Disease; Electroencephalography; Encephalopathies; Epilepsy; Failure; Feasibility Studies; Frequencies; Goals; Gold; Health; High Prevalence; Hour; Hypoxia; Image Analysis; Individual; Injury; Innovative Therapy; Intervention; Lead; Learning; Life; Magnetic Resonance Imaging; Measures; Metabolism; Methods; Monitor; Morbidity - disease rate; Motion; Motor; Near-Infrared Spectroscopy; Neonatal; Newborn Infant; Outcome; Oxygen; Oxygen Consumption; Perinatal Brain Injury; Pharmaceutical Preparations; Population; Populations at Risk; Protocols documentation; Public Health; Recovery; Reperfusion Therapy; Secondary to; Sedation procedure; Severities; Spectrum Analysis; Staging; System; Term Birth; Testing; Therapeutic; Time; base; brain health; brain volume; cerebral blood volume; cerebral oxygenation; disability; excitotoxicity; improved; inclusion criteria; indexing; infant outcome; innovation; meetings; natural hypothermia; neonatal care; neonatal encephalopathy; neonate; neurobehavioral test; response; screening; success; tool; treatment response; Accounting; Acute; Affect; Age; Anisotropy; Behavioral; Blood; Brain Hypoxia-Ischemia; Brain Injuries; Cell Death; Cerebrovascular Circulation; Cerebrum; Cognitive; Control Groups; Detection; Devices; Diffuse; Diffusion; Disease; Electroencephalography; Encephalopathies; Epilepsy; Failure; Feasibility Studies; Frequencies; Goals; Gold; Health; High Prevalence; Hour; Hypoxia; Image Analysis; Individual; Injury; Innovative Therapy; Intervention; Lead; Learning; Life; Magnetic Resonance Imaging; Measures; Metabolism; Methods; Monitor; Morbidity - disease rate; Motion; Motor; Near-Infrared Spectroscopy; Neonatal; Newborn Infant; Outcome; Oxygen; Oxygen Consumption; Perinatal Brain Injury; Pharmaceutical Preparations; Population; Populations at Risk; Protocols documentation; Public Health; Recovery; Reperfusion Therapy; Secondary to; Sedation procedure; Severities; Spectrum Analysis; Staging; System; Term Birth; Testing; Therapeutic; Time; base; brain health; brain volume; cerebral blood volume; cerebral oxygenation; disability; excitotoxicity; improved; inclusion criteria; indexing; infant outcome; innovation; meetings; natural hypothermia; neonatal care; neonatal encephalopathy; neonate; neurobehavioral test; response; screening; success; tool; treatment response

DESCRIPTION (provided by applicant): Neonatal encephalopathy (NE) due to hypoxia-ischemia is a major public health concern as it occurs in 6/1000 live term births and has devastating consequences. Many affected neonates suffer lifelong motor disabilities and epilepsy, but increasingly the high prevalence of cognitive and behavioral disabilities is becoming appreciated. In hypoxia-ischemia there is a decrease in blood and oxygen delivery, followed by reperfusion with transient energy recovery. What follows is a "window of opportunity" where excitotoxicity and associated increased cerebral metabolism eventually lead to secondary energy failure and irreversible cell death. In this window, therapeutic hypothermia (TH) is currently the only treatment available with proven efficacy. TH acts primarily by decreasing cerebral metabolism, thus preserving energy stores. Although the current gold standard for brain injury detection is magnetic resonance imaging (MRI), MRI is impractical as a screening tool and cannot provide bedside monitoring to optimize individual responses to therapies. Commercially available continuous wave (CW) near infrared spectroscopy (NIRS) systems provide bedside measures of cerebral oxygen saturation (SO2) but SO2 alone cannot assess oxygen metabolism, as oxygen delivery is not taken into account. What is needed is a bedside tool that can monitor cerebral metabolism to detect elevations in metabolism that suggest evolving hypoxic-ischemic injury, and decreases in metabolism that suggest response to therapy. Cerebral oxygen consumption (CMRO2) is a direct measure of cerebral metabolism and therefore we propose to measure an index of CMRO2 at the bedside using the innovative combination of Frequency Domain Near-Infrared Spectroscopy (FDNIRS) and Diffuse Correlation Spectroscopy (DCS). Our initial studies show that CMRO2 is elevated in neonates with MRI evidence of perinatal brain injury, and confirm that neonates on TH have significantly lower CMRO2 than normal controls. Following these exciting results, and in response to the RFA PAR-10-230 "Innovative Therapies and Tools for Screenable Disorders in Newborns" we now propose a feasibility study to determine if FDNIRS-DCS can screen for involvement, assess response to treatment, and predict outcomes in one of the largest neonatal populations requiring early screening and immediate intervention: neonatal encephalopathy. To assess early outcomes we propose an innovative combination of advanced neurobehavioral testing, regional FDNIRS-DCS measures and quantitative MRI analysis using MRIs obtained without sedation. If our hypotheses prove true, we will be poised to determine if bedside indices of CMRO2 provided by FDNIRS-DCS can optimize TH for individual neonates, thereby improving neurodevelopmental outcomes. Success at this stage will also allow exploration of the potential for FDNIRS-DCS to determine the additional benefits of emerging new treatments for NE and to screen for other treatable neonatal disorders.

描述（由申请人提供）：由于缺氧 - 异常而引起的新生儿脑病（NE）是一个主要的公共卫生问题，因为它发生在6/1000个实期分娩中，并带来了毁灭性的后果。许多影响的新生儿遭受了终生的运动障碍和癫痫病，但越来越多的认知和行为障碍的患病率越来越高。在低氧 - 缺血性中，血液和氧气递送降低，然后再灌注瞬时能量回收。接下来是“机会之窗”，其中兴奋性毒性和相关的脑代谢增加最终导致次级能量失效和不可逆的细胞死亡。在此窗口中，治疗性体温过低（Th）目前是唯一可获得的可效果的治疗方法。这主要是通过减少脑代谢，从而保留能量储存的作用。尽管目前用于脑损伤检测的金标准是磁共振成像（MRI），但MRI是不切实际的筛查工具，无法提供床边监测以优化对治疗的单个反应。在红外光谱（NIRS）附近的市售连续波（CW）提供脑氧饱和度（SO2）的床边测量（SO2），但仅SO2无法评估氧代谢，因为不考虑氧递送。所需的是一种床头工具，可以监测脑代谢，以检测代谢的升高，这表明会不断发展的缺氧性损伤，并降低了新陈代谢的降低，暗示对治疗的反应。脑氧的消耗（CMRO2）是脑代谢的直接衡量，因此我们建议使用频域近红外光谱（FDNIR）和扩散相关光谱（DCS）的创新组合来测量床边CMRO2的指数。我们的初步研究表明，CMRO2在新生儿中具有围产期脑损伤的MRI证据的升高，并确认TH上的新生儿的CMRO2明显低于正常对照。遵循这些令人兴奋的结果，并回应RFA PAR-10-230“新生儿中可筛选疾病的创新疗法和工具””现在，我们提出了一项可行性研究，以确定FDNIRS-DCS是否可以筛选筛查，评估对治疗的反应，并预测最大的新生儿群体中的临时筛查，需要早期筛查和直接审查。为了评估早期结果，我们提出了晚期神经行为测试，区域FDNIRS-DCS测量和定量MRI分析的创新组合，使用未经镇静而获得的MRI分析。如果我们的假设被证明是正确的，我们将有望确定FDNIRS-DC提供的CMRO2的床边指数是否可以优化单个新生儿的TH，从而改善神经发育结果。在此阶段的成功还将允许探索FDNIRS-DCS确定新的NE治疗的其他好处，并筛查其他可治疗的新生儿疾病的其他好处。