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

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2020 · $239,280

## Abstract

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.

## Key facts

- **NIH application ID:** 10054870
- **Project number:** 1R21AG065816-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Felix W Wehrli
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $239,280
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10054870

## Citation

> US National Institutes of Health, RePORTER application 10054870, Noninvasive Quantification of Age-Related Alterations in Sleep-Dependent CMRO2 Attenuation Using EEG-Correlated MRI (1R21AG065816-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10054870. Licensed CC0.

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