# Enhanced Deuterium Metabolic Imaging (DMI) of Metabolic Reprogramming in Brain Tumors

> **NIH NIH R01** · STANFORD UNIVERSITY · 2023 · $610,360

## Abstract

Abstract
 Deuterium metabolic imaging (DMI) is an emerging MRI technique whereby deuterated substrates and
their metabolic products are imaged in vivo. A primary application is the study of energy metabolism, a
fundamental process for virtually all cells in the body. In particular, glucose (Glc) metabolism plays a critical
role in cancer, with two key metrics of tumor metabolism being total glucose consumption and the relative
fraction of Glc undergoing glycolysis (GLY) versus oxidative phosphorylation (OXPHOS). In contrast to normal
tissues, most cancers exhibit a preponderance of GLY over OXPHOS. Known as the Warburg effect or, more
generally metabolic reprogramming, these alterations are particularly pronounced in glioma and other brain
tumors. Elevated GLY in high-grade brain tumors has been shown to be a marker of tumor growth and
aggressiveness. From a therapeutic perspective, studies strongly support that this Warburg phenotype is
necessary and sufficient for the cancer process, which provides the framework of a highly novel therapeutic
strategy targeted at affecting these metabolic pathways. We contend that clinical translation is presently
impeded not so much by a lack of agents, but by the difficulty in measuring these fundamental aspects of
tumor metabolism in vivo.
 Of the available imaging techniques, 18F-FDG-PET is well-established for imaging glucose uptake, whereas
robust in vivo measurements of GLY and OXPHOS are considerably more challenging. Triple 15O-PET can be
used to assess oxygen consumption (and hence OXPHOS) but is clinically problematic due to the 2-min half-
life of 15O and the challenges of coordinating multiple inhaled radioactive gases. MRI of hyperpolarized 13C-
labeled pyruvate has been shown capable of assessing tumor GLY/OXPHOS ratios; however, this technique is
very expensive with limited availability and unique challenges. More recently, the feasibility of using
conventional 2H MRSI of deuterated glucose to measure both GLY and OXPHOS has been successfully
demonstrated. Given the ubiquity of 3T scanners, we contend that 3T DMI would have maximal clinical impact,
and initial results for the human brain reported at 4T, in combination with our own 3T DMI data, indicate limited
spatial resolution, low SNR, and correspondingly long scan times are the primary limitations. This technical
development project will address these challenges by enhancing DMI via the incorporation of multimodal
information. Noting that 1H MRI and FDG-PET share significant mutual anatomic and metabolic information
with DMI, we propose to significantly enhance 3T DMI using signal processing and machine learning
approaches analogous to techniques using MRI to enhance FDG-PET resolution and SNR. The overall goal is
to demonstrate enhanced DMI acquisitions and image processing pipelines for maximal clinical impact, with
the initial application being the imaging of the Warburg effect in brain tumors.

## Key facts

- **NIH application ID:** 10593853
- **Project number:** 1R01CA277832-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Daniel M Spielman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $610,360
- **Award type:** 1
- **Project period:** 2023-02-01 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10593853

## Citation

> US National Institutes of Health, RePORTER application 10593853, Enhanced Deuterium Metabolic Imaging (DMI) of Metabolic Reprogramming in Brain Tumors (1R01CA277832-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10593853. Licensed CC0.

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