Noninvasive Quantification of Age-Related Alterations in Sleep-Dependent CMRO2 Attenuation Using EEG-Correlated MRI

项目摘要 相当一部分美国人患有不同程度的失眠，尤其是 在老年人中很常见。睡眠中断会对认知功能和记忆产生不利影响，并可能 导致与年龄相关的认知能力下降。大脑是一个高度新陈代谢的器官，但在慢波期间 睡眠、大脑葡萄糖和氧代谢下降。大脑新陈代谢的这种减少可能是至关重要的 对于长期的动态平衡，而无法在睡眠期间充分降低大脑能量消耗可能 导致氧化损伤。先前研究慢波睡眠期间大脑代谢变化的工作依赖于 关于侵入性的方法。在初步工作中，我们开发了一种基于MRI的非侵入性方法，称为 OxFlow，无创性地量化脑氧耗代谢率(CMRO2)在一个温度- 数秒的临时分辨率，以及同时进行的扫描仪内脑电监测。OxFlow量化CMRO2 用Fick原理同时测量静脉血氧饱和度和脑总血氧饱和度 流量(TCBF)。该方法的可行性已在神经代谢异常的受试者中得到验证。 在清醒状态和睡眠状态下测量拉米。在本项目的目标1中，我们建议进一步降低 开发用于睡眠研究的OxFlow方法。具体地说，我们将修改梯度结构，以- 弱化噪音，以促进受试者开始和维持睡眠的能力。我们还将优化 脑电滤波程序最大限度地减少MRI梯度引起的电子噪声的干扰，以可靠地允许 同时的脑电记录需要作为确定受试者意识阶段的一种手段。在AIM 2我们将检验这一假设，即在年长的受试者中，慢波睡眠与觉醒到睡眠的减少有关。 与年轻受试者相比，CMRO2受试者睡眠减少。我们将通过以下主题来解决这个假设 12名年轻受试者和12名年长受试者(25-40岁对60-80岁)接受MRI/EEG联合睡眠方案。本研究 将为测量睡眠依赖的大脑能量调节提供新的非侵入性方法，并开始 展示其在脑老化和痴呆症研究中的效用。

Project Summary A significant fraction of the US population suffers from various degrees of insomnia, conditions particularly prevalent in the elderly. Fractured sleep has adverse effects on cognitive function and memory, and may contribute to age-related cognitive decline. The brain is a highly metabolic organ, but during slow-wave sleep, cerebral glucose and oxygen metabolism decline. This reduction in brain metabolism may be critical for long-term homeostasis, while an inability to adequately lower brain energy expenditure during sleep may lead to oxidative injury. Prior work examining alterations in brain metabolism during slow-wave sleep relied on invasive methods. We have, in preliminary work, developed a noninvasive MRI-based method, termed OxFlow, to noninvasively quantify the cerebral metabolic rate of oxygen consumption (CMRO2) at a tem- poral resolution of seconds, along with concurrent, in-scanner EEG monitoring. OxFlow quantifies CMRO2 via Fick's principle using concurrent measurement of venous O2 saturation and total brain cerebral blood flow (tCBF). The approach's feasibility has been demonstrated in test subjects in whom neurometabolic pa- rameters were measured during wakefulness and sleep. In Aim 1 of this project we propose to further de- velop the OxFlow method for use in sleep research. Specifically, we will modify the gradient structure to at- tenuate acoustic noise so as to facilitate subjects' ability to initiate and maintain sleep. We will also optimize EEG filtering procedures to minimize interference of MRI gradient-induced electronic noise to reliably allow simultaneous EEG recordings needed as a means to establish the subject's stage of consciousness. In Aim 2 we will test the hypothesis that in older subjects, slow-wave sleep is associated with a reduced awake-to- sleep decrement in CMRO2 as compared to younger subjects. We will address this hypothesis by subjecting 12 young and 12 older subjects (25-40 vs. 60-80 years) to a combined MRI/EEG sleep protocol. This study will provide new noninvasive methods for measuring sleep dependent brain energy regulation and begin to demonstrate its utility in research on brain aging and dementia.