# Imaging  brain glucose uptake by onVDMP MRI in Huntington's Disease

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2020 · $464,604

## Abstract

Huntington's disease (HD) is the most common inherited neurodegenerative disorder caused by an expanded
DNA trinucleotide CAG in the Huntingtin gene. The clinical diagnosis of HD is based on the presence of
movement disorders. However, subtle-to-prominent brain functional changes can precede by years the motor-
based onset. Given the availability of a genetic testing, it is possible to identify which subjects will develop the
disease before motor symptoms are present. This provides a unique opportunity to identify potential
biomarkers, which would be of unquestionable value for promoting the development of disease-modifying
therapies. To date, proven neuroprotective strategies for HD remain elusive although there has been a rapid
progress in understanding of the pathogenesis. Part of the problem is that most of the clinical trials have
attempted intervening when the degenerative process is already advanced making it difficult even for the most
effective therapy to demonstrate any benefit. Thus, availability of sensitive biomarkers during the premanifest
phase is critical for determining an optimal time to initiate the treatment, as well as for reliably evaluating
efficacy in clinical trials. The brain is an energy-demanding organ that weighs ~2% of the whole body but
consumes ~20% of total body glucose in the resting state. Strong evidence of early glucose hypometabolism
in the HD brain has been reported. Whether glucose hypometabolism in premanifest HD represents an
irreversible damage or whether it predicts the brain structural changes remains unknown. Glucose uptake in
brain has been assessed mostly using 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography.
Glucose chemical exchange saturation transfer (glucoCEST) MRI is a recently developed technique that can
detect unlabeled glucose at physiologically relevant concentrations using proton-only MRI scanners without the
requirement of additional hardware. This new method allows the detection of low concentration glucose
through the chemical exchange of protons between hydroxyl groups and water. However, the sensitivity of the
conventional glucoCEST MRI is limited due to the fast-exchange rates of these hydroxyl protons (>3000 Hz).
In order to improve the labeling efficiency of such protons, we recently developed an on-resonance variable
delay multiple pulse (onVDMP) MRI sequence. Our preliminary data show an exciting discovery, namely that
this technique is sensitive to differentiate the glucose uptake and clearance in HD mouse brain from controls.
The objective of this R21 is to determine whether onVDMP MRI measures of glucose uptake can serve as
sensitive biomarkers for characterizing early disease progression and assessing response to treatment in HD
mice. In Aim 1, we will identify spatiotemporal dynamics of glucose uptake and clearance in HD mouse brain
and to determine whether impaired glucose uptake and clearance progresses with disease and predates and
predicts selective brain ...

## Key facts

- **NIH application ID:** 10034195
- **Project number:** 1R21NS118079-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Wenzhen Duan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $464,604
- **Award type:** 1
- **Project period:** 2020-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10034195

## Citation

> US National Institutes of Health, RePORTER application 10034195, Imaging  brain glucose uptake by onVDMP MRI in Huntington's Disease (1R21NS118079-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10034195. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
