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

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(申请人提供)：由于缺氧-缺血引起的新生儿脑病(NE)是一个主要的公共卫生问题，因为它发生在每1000名活产儿中，并具有毁灭性的后果。许多受影响的新生儿患有终身运动障碍和癫痫，但认知和行为障碍的高患病率越来越受到重视。在缺氧-缺血时，血液和氧气输送减少，随后是短暂能量恢复的再灌流。接下来是一个“机会之窗”，兴奋毒性和相关的大脑新陈代谢增加最终导致继发性能量衰竭和不可逆转的细胞死亡。在这一窗口中，治疗性低温(TH)是目前唯一有效的治疗方法。TH的作用主要是通过降低大脑新陈代谢，从而保存能量储备。虽然目前脑损伤检测的金标准是磁共振成像(MRI)，但作为一种筛查工具，MRI是不切实际的，无法提供床边监测来优化个人对治疗的反应。商业上可用的连续波(CW)近红外光谱(NIRS)系统提供了脑血氧饱和度(SO2)的床边测量，但仅靠SO2无法评估氧代谢，因为没有考虑氧气输送。需要的是一种床边工具，可以监测大脑代谢，以检测代谢水平的上升，表明正在发生的缺氧缺血性损伤，以及代谢下降，表明对治疗的反应。脑耗氧量(CMRO2)是大脑代谢的直接指标，因此我们建议在床边使用频域近红外光谱(FDNIRS)和漫相关光谱(DCS)的创新组合来测量CMRO2指数。我们的初步研究表明，在有围产期脑损伤的MRI证据的新生儿中，CMRO2升高，并证实TH组的新生儿CMRO2显著低于正常对照组。在这些令人振奋的结果之后，并针对RFA PAR-10-230“新生儿可筛查障碍的创新疗法和工具”，我们现在提出一项可行性研究，以确定FDNIRS-DCS是否可以在需要早期筛查和立即干预的最大新生儿人群之一：新生儿脑病中进行筛查，评估治疗反应，并预测预后。为了评估早期结果，我们提出了一种创新的组合，结合先进的神经行为测试、区域性FDNIRS-DCS测量和使用不使用镇静剂的磁共振成像进行定量MRI分析。如果我们的假设被证明是正确的，我们将准备好确定FDNIRS-DCS提供的床边CMRO2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。在这一阶段的成功还将使FDNIRS-DCS的潜力得以探索，以确定新出现的NE治疗方法的额外好处，并筛选其他可治疗的新生儿疾病。