# Imaging cerebral metabolic impairment in AD using Deuterium MRI

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $685,840

## Abstract

Project Summary/Abstract
This project will investigate deuterium (2H) metabolic imaging (DMI) as a quantitative, stable-isotope MR
molecular imaging approach to probe cerebral metabolic impairment in Alzheimer’s Disease (AD). AD and
related dementias represent a growing public health concern with tremendous impact on patients and their
families. Efforts to treat AD effectively are partially confounded by different hypotheses regarding its initiation
and progression, as reflected by the range of highly informative imaging methods used to study AD, including
positron emission tomography (PET) and advanced magnetic resonance imaging (MRI). Dysfunctional glucose
metabolism is both an early and critical determinant of disease progression, and the glucose derivative
[18F]Fluorodeoxyglucose (FDG) has been widely used to probe cerebral metabolism in AD patients. While this
may reflect a decrease in glucose demand, it does not inform on metabolism itself. Furthermore, FDG-PET has
significant limitations in accessibility, cost and accuracy, and provides no information on metabolic processes
beyond glucose uptake and phosphorylation. Thus, while FDG-PET shows the potential of a metabolic biomarker,
a sensitive and practical imaging method is critically needed.
Deuterium MRI is a novel and quantitative metabolic imaging approach that provides direct visualization of the
uptake and meteabolic fate of glucose on timescales and sensitivities that are not achievable with 1H or
hyperpolarized 13C MR spectroscopic imaging. Our initial data using DMI in a J20 mouse model of AD show that
reduced glucose metabolism to lactate and reduced HDO enrichment can be observed compared to age-
matched healthy controls. Building on these results, we propose to develop new DMI approaches for assessment
of glucose metabolism in the live brain, and validate these techniques in healthy and AD mice, as well as in
healthy volunteers. In Aim 1, we will investigate three separate strategies to assess glucose metabolism with 2H
MRI: metabolism using [6,6’-2H]glucose, HDO enrichment using [U-2H]glucose, and accumulation using [2,2’-
2H2]2-deoxyglucose. In Aim 2, we will apply these three approaches to preclinical models of AD and compare
results to FDG-PET. In Aim 3, we will develop hardware for human translation at 7T and will characterize brain
metabolism in healthy volunteers using [6,6’-2H]glucose and [U-2H]glucose. Successful completion of this project
will improve our understanding of glucose metabolism in AD, provide a foundation for future clinical studies in
patients with AD, improve clinical management, help refine therapy regimens and, ultimately lead to better
outcome and quality of life for people living with AD.

## Key facts

- **NIH application ID:** 10796893
- **Project number:** 5R01AG080981-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jeremy William Gordon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $685,840
- **Award type:** 5
- **Project period:** 2023-03-01 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10796893

## Citation

> US National Institutes of Health, RePORTER application 10796893, Imaging cerebral metabolic impairment in AD using Deuterium MRI (5R01AG080981-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10796893. Licensed CC0.

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