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

使用脑电图相关 MRI 对睡眠依赖性 CMRO2 衰减中与年龄相关的变化进行无创定量

• 批准号: 10054870
• 负责人: Felix W Wehrli
• 金额: $ 23.93万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10054870
• 关键词: Acoustics; Address; Adverse effects; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Ballistics; Blood; Brain; Brain Injuries; Cerebrovascular Circulation; Cerebrum; Chronic; Conscious; Data; Dementia; Dependence; Derivation procedure; Development; Diabetes Mellitus; Elderly; Electroencephalography; Energy Metabolism; Fick method; Fracture; Frequencies; Functional Magnetic Resonance Imaging; Future; Glucose; Heart Diseases; Homeostasis; Human; Hypertension; Image; Infusion procedures; Internal jugular vein structure; Lead; Light; Magnetic Resonance Imaging; Maintenance; Measurement; Measures; Memory; Memory impairment; Mental Depression; Metabolic; Metabolism; Methodology; Methods; Monitor; Morphologic artifacts; Neurodegenerative Disorders; Noise; Organ; Oxygen; Oxygen Consumption; Parkinson Disease; Peat; Performance; Physiologic pulse; Physiological; Population; Prevalence; Procedures; Property; Protocols documentation; Radial; Ramp; Regulation; Reporting; Research; Risk; Role; Sampling; Scanning; Seminal; Signal Transduction; Sleep; Sleep Deprivation; Sleep Disorders; Sleep Stages; Sleep disturbances; Sleeplessness; Slow-Wave Sleep; Stroke; Structure; Synaptic Transmission; Techniques; Tenuate; Testing; Tracer; Trapezoid bone structure; Venous; Wakefulness; Work; age related; aging brain; attenuation; awake; base; brain health; brain metabolism; cognitive function; cohort; imaging modality; improved; insight; metabolic rate; neurovascular; non rapid eye movement; oxidative damage; peer; sleep onset; sleep quality; temporal measurement; young adult

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.

项目概要 很大一部分美国人患有不同程度的失眠症，特别是 多见于老年人。睡眠不足会对认知功能和记忆力产生不利影响，并可能 导致与年龄相关的认知能力下降。大脑是一个高度代谢的器官，但在慢波期间 睡眠时，脑内葡萄糖和氧代谢下降。大脑新陈代谢的减少可能至关重要 为了长期的体内平衡，而无法在睡眠期间充分降低大脑能量消耗可能会 导致氧化损伤。先前研究慢波睡眠期间大脑代谢变化的研究依赖于 关于侵入性方法。在前期工作中，我们开发了一种基于 MRI 的无创方法，称为 OxFlow，以无创方式量化某一温度下的大脑耗氧代谢率 (CMRO2) 秒级的口腔分辨率，以及并发的扫描仪内脑电图监测。 OxFlow 量化 CMRO2 根据菲克原理，同时测量静脉 O2 饱和度和脑总血量 流量（tCBF）。该方法的可行性已在神经代谢异常的测试对象中得到证明。 在清醒和睡眠期间测量参数。在该项目的目标 1 中，我们建议进一步 开发用于睡眠研究的 OxFlow 方法。具体来说，我们将梯度结构修改为 - 减弱噪音，以促进受试者启动和维持睡眠的能力。我们也会优化 EEG 滤波程序可最大限度地减少 MRI 梯度引起的电子噪声的干扰，从而可靠地允许 需要同步脑电图记录作为确定受试者意识阶段的手段。瞄准 2 我们将检验以下假设：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，CMRO2 的睡眠减少。我们将通过以下方式来解决这个假设 12 名年轻受试者和 12 名老年受试者（25-40 岁与 60-80 岁）接受 MRI/EEG 联合睡眠方案。这项研究 将提供新的非侵入性方法来测量睡眠依赖的大脑能量调节，并开始 展示其在大脑衰老和痴呆症研究中的实用性。