A Multimodality Approach to Estimating Newborn Brain Oxygen Metabolism (CMRO2)

描述(申请人提供)：围产期脑损伤仍然是婴儿死亡和发病的重要原因，每1000名活产中就有6名以上发生。它是脑瘫、癫痫、复杂行为障碍和智力障碍的常见原因。目前认为，大多数围产期脑损伤是由于氧化代谢障碍造成的，其中神经元损伤是由缺血引起的，随后是再灌注或遗传性代谢途径缺陷在围产期表达。由于神经元的活动在时间上与新陈代谢或氧气消耗密切相关，因此直接测量大脑氧气消耗可能是最直接的神经元健康衡量标准。我们相信，测量生命第一周的耗氧量有可能改善脑损伤的早期分层，并更好地预测结果。正电子发射断层扫描(PET)可以提供氧气消耗的直接信息，但辐射暴露和缺乏可用性使常规使用不切实际。我们的目标是建立一种安全、无创的多模式方法来估计新生儿局部脑耗氧量。我们建议结合频域近红外光谱(FD-NIRS)和动脉自旋标记(ASL)的磁共振(MR)技术来无创性和实时地估计新生儿脑耗氧量。为了实现这一目标，需要取得技术进步：1)构建针对新生儿头部的多通道MRI线圈，以优化信噪比并缩短扫描时间；2)构建兼容的光学探头，与MRI同时测量血红蛋白氧饱和度；3)利用MRI的结构信息，优化用于量化大脑光学参数和估计耗氧量的算法。为了验证我们的耗氧量测量作为脑损伤指标的有效性，我们将测试20名有围产期脑损伤风险的婴儿的耗氧量，并将3个月时的耗氧量与脑体积相关联。公共卫生相关性：氧耗代谢率(CMRO2)是衡量损伤后大脑健康的最佳指标，但目前尚无非侵入性方法可用。32-Chanel磁共振成像和频域近红外光谱分析相结合，为我们最脆弱和最难评估的人群之一--新生儿--提供了安全、快速、无创地估计CMRO2绝对值的潜力。

DESCRIPTION (provided by applicant): Perinatal brain injury remains a significant cause of infant mortality and morbidity, occurring in over 6 out of every 1,000 live births. It is a common cause of cerebral palsy, seizures, complex behavioral disorders and intellectual impairment. It is now believed that the majority of perinatal brain injury is due to impairment of oxidative metabolism, with neuronal injury due to ischemia followed by reperfusion or inherited defects in metabolic pathways expressed in the perinatal period. With neuronal activity closely linked in time to the metabolism or consumption of oxygen direct measures of cerebral oxygen consumption likely provide the most direct measure of neuronal health. We believe that a measure of oxygen consumption during the first week of life has the potential to improve early stratification of brain injury and better predict outcome. Positron Emission Tomography (PET) can provide direct information on oxygen consumption but the radiation exposure and lack of availability make routine use impractical. Our goal is to establish a safe, noninvasive multimodal method to estimate newborn regional cerebral oxygen consumption. We propose to combine Frequency Domain Near Infrared Spectroscopy (FD-NIRS) and the Magnetic Resonance (MR) technique of Arterial Spin Labeling (ASL) to estimate newborn cerebral oxygen consumption noninvasively and in real time. To do achieve this goal, technical advances are needed: 1) build a multichannel MRI coil tailored to the newborn head to optimize the SNR and reduce the scanning time; 2) build a compatible optical probe to measure hemoglobin oxygen saturation simultaneously with MRI; 3) take advantage of the MRI structural information for optimization of the algorithms used to quantify brain optical parameters and estimate oxygen consumption. To validate our measurement of oxygen consumption as an indicator of brain injury we will test our measure of oxygen consumption in 20 infants at risk for perinatal brain injury and correlate oxygen consumption with brain volume at 3 months. PUBLIC HEALTH RELEVANCE: The metabolic rate of oxygen consumption (CMRO2) is the best measure of brain health after injury yet there are no non-invasive methods available. Combined 32-chanel MRI and frequency domain near infrared spectroscopy offer the potential to safely perform fast noninvasive estimates of absolute CMRO2 in one of our most vulnerable and difficult to assess populations: newborns.