Optical Monitoring of Cerebral Oxygenation in Infants

描述（由申请人提供）：由于神经学检查和当前床边方法的不敏感性，通常很难确定婴儿脑损伤的时间，演变和程度。生命的第一年是大脑发育的关键时期，因为在这段时间里可能会发生几个月甚至几年不被发现的异常。脑异常的延迟诊断导致延迟干预，并可能对结果产生负面影响。为了及时发现新生儿脑损伤，了解正常发育轨迹，区分异常和正常轨迹，并提供损伤对脑发育后果的早期评估，需要一种安全的床边技术来定量和可靠地监测区域脑健康和发育。我们相信，通过结合两种光学非侵入技术，我们可以实现这一目标。频域近红外光谱（FD-NIRS）提供床边监测区域脑血容量和氧合，而漫射相关光谱（DCS）测量区域脑血流速度。这两种技术的结合提供了脑氧代谢的估计。我们的假设是，与耗氧量相关的光学测量将与临床评估和脑损伤的结果最相关。在本提案中，我们将推进光学方法来量化基线脑血流量和耗氧量，将这些测量结果与动物和人类的MRI测量结果进行验证，并在3D分割MRI头部上进行蒙特卡罗模拟来评估该方法的准确性。然后，我们将对健康和患病婴儿在一岁期间进行纵向FD-NIRS和DCS测量。通过比较健康婴儿和患病婴儿的结果，我们将能够验证我们的假设，即氧气消耗的光学测量可以检测大脑损伤及其对大脑发育的影响。脑损伤检测和分层将与临床诊断相关，使用MRI， EEG和神经学检查；正常和异常的大脑发育轨迹将与我们的行为和神经生理发育测试的结果相关联，如果有临床随访检查的话。该项目的长期目标是建立FD-NIRS和DCS光学技术，作为监测新生儿大脑健康以及正常和病变大脑代谢和血流动力学发育的新标准。这项新措施可能对新生儿护理产生影响，促进早期干预以防止进一步损害，提供治疗“机会之窗”的估计，帮助对治疗干预的新生儿进行分层，并成为评估治疗反应的工具。

DESCRIPTION (provided by applicant): It is often difficult to determine the timing, evolution and extent of brain injury in infants due to the insensitivity of the neurological exam and of current bedside methods. The first year of life is a critical period in brain development, as abnormalities that can go undetected for months or even years may occur during this time. Delayed diagnosis of cerebral abnormalities leads to delayed intervention and may have a negative impact on outcome. To promptly detect neonatal brain injury, to understand normal developmental trajectories, to distinguish abnormal from normal trajectories, and to provide early assessment of the consequences of injury on brain development, a safe, bedside technique is needed to quantitatively and reliably monitor regional brain health and development. We believe we can achieve this goal by combining two optical noninvasive techniques. Frequency-domain near-infrared spectroscopy (FD-NIRS) provides bedside monitoring of regional cerebral blood volume and oxygenation, while diffuse correlation spectroscopy (DCS) measures regional cerebral blood velocity. The combination of the two techniques provides an estimate of cerebral oxygen metabolism. Our hypotheses are that the optical measure related to oxygen consumption will correlate best with clinical assessment and outcome of brain damage. In this proposal, we will advance the optical method to quantify baseline cerebral blood flow and oxygen consumption, validate these measurements against MRI measurements in animals and humans, and assess the accuracy of the method with Monte Carlo simulations on 3D segmented MRI heads. We will then perform longitudinal FD-NIRS and DCS measurements in healthy and sick infants during the first year of life. By comparing results in healthy and sick infants, we will be able to test our hypotheses that the optical measure of oxygen consumption can detect brain damage and its effect on brain development. Brain damage detection and stratification will be correlated with clinical diagnosis using MRI, EEG and neurological exams; normal and abnormal brain development trajectories will be correlated with the results of our behavioral and neuro-physiological development tests and, when available with clinical follow-up exams. The long-term objective of the proposed project is to establish FD-NIRS and DCS optical techniques as new standards for monitoring neonatal brain health and metabolic and hemodynamic development in the normal and diseased brain. This new measure could have an impact on neonatal care, prompt early intervention to prevent further damage, provide an estimate of the "window of opportunity" for treatment, help stratify neonates for therapeutic interventions, and become a tool for evaluating response to therapy.