# Deuterium metabolic imaging (DMI) of neurological disease

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $661,245

## Abstract

PROJECT SUMMARY
Non-invasive imaging of metabolic pathways in neurological disease has been a long-standing goal to monitor
disease progression or therapy efficacy. Clinicians have in reality only one metabolic imaging tool, which is
detection of intravenously administered 2-18F-fluoro-2-deoxy-D-glucose (FDG) with positron emission
tomography (PET). Its unrivaled sensitivity makes FDG-PET a mainstay application for cancer detection
outside of the brain. However, the high uptake of FDG by normal brain drastically reduces the image contrast
and the usefulness of FDG-PET in studying neurological disease. 1H and 13C MR spectroscopic imaging
(MRSI), and hyperpolarized 13C MRSI are promising methods but have failed to reach clinical significance due
to a variety of reasons including technical complexity and lack of robustness and/or sensitivity.
Substrates labeled with deuterium (2H) have been used for decades to study whole body human metabolism
by detecting the 2H label in downstream metabolic products in plasma or tissue samples using mass
spectroscopy or magnetic resonance spectroscopy (MRS). Our first-in-man deuterium metabolic imaging (DMI)
maps of glucose metabolism in healthy brain and DMI maps showing the distribution of the “Warburg-effect” in
patients with high grade brain tumors illustrate that DMI has the potential to become a widely applicable brain
imaging method with strong clinical utility. The proposal is organized around three specific aims that will
establish the clinical applicability, scientific validity and reproducibility of DMI. As part of Aim 1, the 2H-based
measurement of glucose metabolism will be validated with `gold-standard' 13C-based MRS on animal and
human brain. The availability of affordable 2H-labeled substrates, such as glucose (and acetate), together with
the relative ease of DMI data acquisition greatly expedites the translation to a clinical 3 Tesla MRI scanner. In
Aim 2 we will optimize the protocol for use of DMI in the clinic, report on reproducibility of the DMI-based
metabolic maps, and explore the metabolic differences detected with DMI in patients diagnosed with primary
and secondary brain tumors.
In the third aim we compare in patients diagnosed with brain tumors the metabolism-based image contrast
observed using DMI with the image contrast detected using FDG-PET. By the completion of the proposed
studies we expect to have a simple, but robust metabolic imaging modality that can provide 3D maps of the
metabolic fate of multiple substrates in a wide range of neurological disorders.

## Key facts

- **NIH application ID:** 9912746
- **Project number:** 5R01EB025840-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** ROBIN A DE GRAAF
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $661,245
- **Award type:** 5
- **Project period:** 2019-04-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9912746

## Citation

> US National Institutes of Health, RePORTER application 9912746, Deuterium metabolic imaging (DMI) of neurological disease (5R01EB025840-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9912746. Licensed CC0.

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