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（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 的足月新生儿中，并具有毁灭性的后果。许多受影响的新生儿患有终生运动障碍和癫痫症，但认知和行为障碍的高患病率越来越受到人们的重视。在缺氧缺血中，血液和氧气输送减少，然后再灌注并短暂恢复能量。接下来是一个“机会之窗”，其中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。在这个窗口中，低温治疗（TH）是目前唯一有效的治疗方法。 TH 主要通过降低脑代谢来发挥作用，从而保存能量储存。尽管目前脑损伤检测的黄金标准是磁共振成像 (MRI)，但 MRI 作为筛查工具并不实用，并且无法提供床边监测来优化个体对治疗的反应。市售连续波 (CW) 近红外光谱 (NIRS) 系统可提供脑氧饱和度 (SO2) 的床边测量，但单独使用 SO2 无法评估氧代谢，因为未考虑氧输送。我们需要的是一种床边工具，可以监测脑代谢，以检测代谢升高（表明正在发生缺氧缺血性损伤）和代谢降低（表明对治疗有反应）。脑耗氧量（CMRO2）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）和漫相关光谱（DCS）的创新组合在床边测量CMRO2指数。我们的初步研究表明，有围产期脑损伤 MRI 证据的新生儿 CMRO2 升高，并证实接受 TH 的新生儿的 CMRO2 显着低于正常对照。继这些令人兴奋的结果之后，并响应 RFA PAR-10-230“新生儿可筛查疾病的创新疗法和工具”，我们现在提出一项可行性研究，以确定 FDNIRS-DCS 是否可以筛查参与情况、评估治疗反应并预测需要早期筛查和立即干预的最大新生儿群体之一的结果：新生儿脑病。为了评估早期结果，我们提出了先进神经行为测试、区域 FDNIRS-DCS 测量和使用无需镇静获得的 MRI 进行定量 MRI 分析的创新组合。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 CMRO2 床边指数是否可以优化个体新生儿的 TH，从而改善神经发育结果。这一阶段的成功还将允许探索 FDNIRS-DCS 的潜力，以确定新兴新疗法对 NE 的额外益处，并筛选其他可治疗的新生儿疾病。