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.

项目摘要 美国人口中有很大一部分患有各种程度的失眠，尤其是条件 在老年人中盛行。破裂的睡眠对认知功能和记忆有不良影响，可能 导致与年龄相关的认知下降。大脑是一个高度代谢器官，但在慢波上 睡眠，脑葡萄糖和氧代谢下降。大脑代谢的这种降低可能至关重要 对于长期的体内平衡，虽然无法充分降低睡眠期间的大脑能量消耗 导致氧化损伤。先前检查慢波睡眠期间脑代谢改变的改变 在侵入性方法上。在初步工作中，我们已经开发了一种基于MRI的非侵入性方法，称为 Oxflow，无创量化氧气消耗的脑代谢率（CMRO2） 多秒钟的孔隙分辨率，以及并发，扫描的脑电图监测。 Oxflow量化了CMRO2 通过Fick的原理，同时测量静脉O2饱和度和全脑脑血 流（TCBF）。该方法的可行性已在测试对象中得到证明，其中神经代谢PA- 在清醒和睡眠期间测量了遮阳器。在该项目的目标1中，我们建议进一步发展 速层在睡眠研究中使用的Oxflow方法。具体而言，我们将将梯度结构修改为AT- 挑战声学噪声，以促进受试者启动和维持睡眠的能力。我们还将优化 脑电图过滤程序，以最大程度地减少MRI梯度诱导的电子噪声的干扰，以可靠地允许 同时需要的脑电图记录是建立主体意识阶段的一种手段。目标 2我们将检验以下假设：在较旧的受试者中，慢波睡眠与降低的清醒相关 与年轻受试者相比，CMRO2的睡眠减少。我们将通过对 12岁和12名较大的受试者（25-40对60 - 80年）组合MRI/EEG睡眠方案。这项研究 将提供新的无创方法来测量依赖睡眠的大脑能量调节并开始 展示了其在大脑衰老和痴呆症研究方面的效用。