# Molecular MRI of Brain Metabolism Enabled by Long-Lived Spin States

> **NIH NIH R01** · NORTH CAROLINA STATE UNIVERSITY RALEIGH · 2020 · $807,392

## Abstract

Molecular MRI of Brain Metabolism enabled by Long-Lived Spin States
Abstract:
Brain function is regulated by molecular signaling and metabolism, however our ability to track metabolic
transformations of individual metabolites deep in the brain pales compared to their central relevance to life. It is
our goal to establish technology for tomographic mapping of metabolites and their metabolic pathways directly
in the brain. Specifically, we aim to map metabolic turnover of13C2-pyruvate, ethyl-13C2-pyruvate, 13C2-Vitamin C,
15N-Vitamin B3, 15N3-Metronidazole (a well-tolerated antibiotic and potential hypoxia probe), and 13C2-Acetate. All
of these markers play critical roles in brain metabolism: pyruvate is a key entry point to energy metabolism and
the tricarboxylic acid (TCA) cycle; Vitamin C (ascorbate) is a vital antioxidant molecule in the brain; Vitamin B3
(Nicotinamide) is a precursor to NAD (nicotinamide adenine dinucleotide), a key regulator of cellular and
organismal homeostasis and redox-status; metronidazole is an antibiotic that undergoes quick turnover in
hypoxic tissue and promises to be a very sensitive hypoxia sensor; Finally, acetate acts as an alternative energy
source for the brain and exhibits rapid and differential uptake and metabolism in, for example, glioblastoma
multiform, a deadly brain cancer.
 From a technological perspective, each of the proposed molecules can carry long-lived hyperpolarization
in NMR-silent, yet RF-accessible quantum states. This property is important because it allows for very long-lived
MRI signals from these molecules that can directly report on chemical transformations via changes in chemical
shift and the scalar coupling network. This ability will allow us to assess kinetics and spatial distribution of reaction
pathways of metabolites at low concentration with sub-second resolution. We have already demonstrated the
fundamental physical principles: i.e. lifetime extension of NMR signals by long-lived spin states. This proposal
transforms our advances into practical, general, and affordable technology which will give us unprecedented
insights into the metabolic basis of brain function with clear potential for scanning broad patient populations.

## Key facts

- **NIH application ID:** 10007222
- **Project number:** 1R01EB029829-01
- **Recipient organization:** NORTH CAROLINA STATE UNIVERSITY RALEIGH
- **Principal Investigator:** Thomas Theis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $807,392
- **Award type:** 1
- **Project period:** 2020-09-15 → 2023-06-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10007222

## Citation

> US National Institutes of Health, RePORTER application 10007222, Molecular MRI of Brain Metabolism Enabled by Long-Lived Spin States (1R01EB029829-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10007222. Licensed CC0.

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