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: 8853307
• 负责人: Patricia Ellen Grant
• 金额: $ 68.45万
• 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/8853307
• 关键词: Accounting; Acute; Affect; Age; Anisotropy; Behavioral; Blood; Blood Volume; Brain; 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 volume; disability; excitotoxicity; improved; inclusion criteria; indexing; infant outcome; innovation; meetings; natural hypothermia; neonatal care; neonate; neurobehavioral test; response; screening; success; tool

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6/1000的活产婴儿中，并具有破坏性后果。许多受影响的新生儿遭受终身运动障碍和癫痫，但越来越多的认知和行为障碍的高患病率正在得到重视。在缺氧-缺血中，血液和氧气输送减少，随后是短暂能量恢复的再灌注。接下来是一个“机会之窗”，兴奋性毒性和相关的脑代谢增加最终导致二次能量衰竭和不可逆的细胞死亡。在这个窗口期，治疗性低温（TH）是目前唯一有效的治疗方法。TH的作用主要是减少大脑代谢，从而保存能量储存。虽然目前脑损伤检测的金标准是磁共振成像（MRI），但MRI作为筛查工具是不切实际的，并且不能提供床边监测以优化个体对治疗的反应。市售的连续波（CW）近红外光谱（NIRS）系统提供了脑氧饱和度（SO2）的床边测量，但SO2单独不能评估氧代谢，因为没有考虑氧气输送。我们需要的是一种床边工具，可以监测脑代谢，以检测代谢的升高，这表明缺氧缺血性损伤的发展，以及代谢的降低，这表明对治疗的反应。脑耗氧量（CMRO 2）是脑代谢的直接测量，因此我们建议使用频域近红外光谱（FDNIRS）和弥散相关光谱（DCS）的创新组合在床边测量CMRO 2指数。我们的初步研究表明，CMRO 2在有围产期脑损伤MRI证据的新生儿中升高，并证实TH新生儿的CMRO 2显著低于正常对照组。根据这些令人兴奋的结果，并响应RFA PAR-10-230“新生儿可筛查疾病的创新疗法和工具”，我们现在提出了一项可行性研究，以确定FDNIRS-DCS是否可以筛查参与，评估对治疗的反应，并预测需要早期筛查和立即干预的最大新生儿人群之一的结局：新生儿脑病。为了评估早期结果，我们提出了先进的神经行为测试，区域FDNIRS-DCS措施和定量MRI分析的创新组合，使用MRI获得无镇静。如果我们的假设被证明是正确的，我们将准备确定FDNIRS-DCS提供的CMRO 2床边指标是否可以优化个体新生儿的TH，从而改善神经发育结局。这一阶段的成功也将允许探索FDNIRS-DCS的潜力，以确定新出现的NE治疗方法的额外益处，并筛选其他可治疗的新生儿疾病。