# Quantitative MRI-based cerebral oxygen metabolism in Alzheimer's disease

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $806,332

## Abstract

Project Summary
Alzheimer's disease (AD) is the most common cause of dementia. Current clinical standard-of-care for
assessing metabolic dysfunction in AD is 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET),
based on a temporoparietal pattern of hypometabolism. However, 1) PET is impractical as a longitudinal
assessment tool because it requires injection of a radioactive tracer, is expensive, and has poorer spatial
resolution and availability compared to MRI; and 2) FDG-PET may not be an accurate measure of neuronal
metabolism, because FDG signal can reflect glucose uptake by microglia and astrocytes for glycolysis, as well
as glucose uptake for oxidative phosphorylation by neurons. The cerebral metabolic rate of oxygen (CMRO2),
reflective of oxidative phosphorylation in neuronal mitochondria, may more directly measure the abnormal
metabolism seen in patients with MCI and AD. Moreover, an MRI-based tool for mapping neuronal metabolism
would allow for longitudinal monitoring both clinically and in therapeutic trials. Therefore, the objective of this
proposal is to develop and optimize an MR-based CMRO2 mapping technique. Aim 1 will be to develop a multi-
echo gradient echo acquisition, integrated with arterial spin labeling to construct oxygen extraction fraction,
cerebral blood flow, and CMRO2 maps using sparsity fingerprinting. Aim 2 will investigate whether this CMRO2
mapping demonstrates regional correlation with well-established measures of AD pathology, including A, tau,
and FDG hypometabolism, the “ATN” stages of AD per the 2018 NIA-Alzheimer's Association research
framework. Aim 3 will investigate the value of our CMRO2 mapping in predicting longitudinal gray matter
degeneration and cognitive decline. If successful, this proposal will develop and validate a noninvasive,
quantitative MR-based tool to diagnose and longitudinally assess cerebral hypometabolism in AD.

## Key facts

- **NIH application ID:** 10933507
- **Project number:** 5R01AG080011-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** GLORIA Chia-Yi CHIANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $806,332
- **Award type:** 5
- **Project period:** 2023-09-30 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10933507

## Citation

> US National Institutes of Health, RePORTER application 10933507, Quantitative MRI-based cerebral oxygen metabolism in Alzheimer's disease (5R01AG080011-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10933507. Licensed CC0.

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