# Supplement for Development and Translation of Specialized Hyperpolarized C-13 MRI Methods for Alzheimer's Disease

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2023 · $403,750

## Abstract

Project Summary/Abstract
The parent Bioengineering Research Partnership has been highly successful over the past 8 years in developing
quantitative, hyperpolarized (HP) stable-isotope MR molecular imaging approaches for monitoring prostate
cancer metabolic reprogramming and response to therapy in a fast 2-minute addition to standard mpMRI exams.
Our Alzheimer’s Disease (AD) colleagues now want to take advantage of the unique HP MRI measurements of
cerebral energy metabolism that is critical for brain function and known to decrease with AD onset. This project
has been developed by our AD multidisciplinary team to develop HP pyruvate and urea MRI as a quantitative
imaging approach to probe cerebral perfusion and metabolic impairment in AD and related dementias that are a
growing public health concern with tremendous impact on patients and their families. Efforts to effectively treat
AD are partially confounded by different hypotheses regarding its initiation and progression, as reflected by the
range of imaging methods used to study AD, including positron emission tomography (PET) and magnetic
resonance imaging (MRI). Dysfunctional glucose metabolism is strongly linked to AD as 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 only
informs on uptake and does not provide accurate information on glycolytic metabolism that decreases with AD.
Furthermore, FDG-PET has significant limitations in accessibility, cost, and accuracy, and provides no
information on metabolic processes downstream of glucose uptake and phosphorylation.
The central goal of this supplement proposal is to develop and apply methods of measuring impaired metabolism
in AD for the first time using advanced HP C-13 MRI. HP pyruvate MRI is an emerging molecular imaging method
that provides dynamic and pathway-specific metabolic information not available with FDG-PET. In the parent
BRP, we have developed methods to greatly improve the coverage, speed, and reliability of HP metabolic
imaging and techniques to co-polarize pyruvate and urea to simultaneously assess metabolism and perfusion in
the prostate. This supplement is designed to extend this approach to measure metabolic impairment in AD.
Specialized techniques will be developed to acquire co-polarized data using [2-13C]pyruvate and [13C]urea,
providing simultaneous assessment of perfusion, glycolysis, and oxidative metabolism in the human brain. These
techniques will then be applied to an initial cohort of patients with mild cognitive impairment (MCI) due to AD and
compared to age-matched controls to assess the magnitude of metabolic changes in AD. The data from this pilot
project will form the foundation for larger studies to evaluate HP 13C MRI as a tool for clinical assessment and
treatment of AD and will have broad applicability for metabol...

## Key facts

- **NIH application ID:** 10715712
- **Project number:** 3U01EB026412-05S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Jeremy William Gordon
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $403,750
- **Award type:** 3
- **Project period:** 2019-06-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10715712

## Citation

> US National Institutes of Health, RePORTER application 10715712, Supplement for Development and Translation of Specialized Hyperpolarized C-13 MRI Methods for Alzheimer's Disease (3U01EB026412-05S1). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10715712. Licensed CC0.

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