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

项目摘要 很大一部分美国人患有不同程度的失眠症， 在老年人中普遍存在。睡眠障碍对认知功能和记忆力有不良影响， 导致与年龄相关的认知能力下降。大脑是一个高度代谢的器官，但在慢波期间， 睡眠时，大脑葡萄糖和氧代谢下降。大脑新陈代谢的减少可能是至关重要的 长期的稳态，而无法充分降低睡眠期间大脑的能量消耗， 导致氧化损伤。之前研究慢波睡眠期间大脑代谢变化的工作依赖于 侵入性方法。在初步工作中，我们开发了一种非侵入性的基于MRI的方法，称为 OxFlow，以非侵入性方式量化脑氧代谢率（CMRO 2）， 沿着的扫描仪内EEG监测的秒级分辨率。OxFlow定量CMRO 2 通过Fick原理，同时测量静脉血氧饱和度和脑血总量 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证实。 在清醒和睡眠期间测量参数。在本项目的目标1中，我们建议进一步- 将OxFlow方法用于睡眠研究。具体来说，我们将修改梯度结构，以- 减弱声学噪声以促进受试者启动和维持睡眠的能力。我们还将优化 EEG滤波程序，以最大限度地减少MRI梯度诱导的电子噪声的干扰， 同步脑电图记录需要作为一种手段，以建立受试者的意识阶段。在Aim中 2我们将检验这样的假设：在老年受试者中，慢波睡眠与觉醒时间减少有关。 与年轻受试者相比，CMRO 2中的睡眠减少。我们将讨论这个假设， 12名年轻受试者和12名老年受试者（25-40岁vs. 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 证明了它在大脑老化和痴呆症研究中的实用性。

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.