# In vivo Mapping of Muscle Specific Metabolism

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $644,539

## Abstract

In vivo Mapping of Muscle Specific Metabolism
ABSTRACT
Phosphorus-31 magnetic resonance spectroscopy (31P-MRS) has long been the method of choice to study
muscle bioenergetics in humans. 31P-MRS measures relative amounts of phosphocreatine (PCr) and adenosine
triphosphate (ATP), and can be used to estimate muscle creatine kinase (CK) kinetics. During exercise, PCr, a
high-energy “reserve” source of ATP, is depleted to meet transient energy demands. The rate of PCr re-synthesis
after exercise is commonly used as a measure of skeletal muscle oxidative phosphorylation (OXPHOS) capacity.
Studies using 31P-MRS and multiple other modalities have suggested that abnormal creatine metabolism and
deficient OXPHOS may contribute to the pathophysiology of aging. In addition, it is well established that muscle
groups vary with respect to these metabolic properties, and also in their response to aging. Despite its strengths,
31P-MRS has low anatomic resolution, and does not readily provide muscle group specific estimates of creatine
metabolism. The currently available option for measuring muscle group specific metabolism is invasive biopsy.
Thus, there is a clear unmet need for high-resolution, non-invasive strategies to assess muscle metabolism
simultaneously across heterogeneous muscle groups.
Our group recently introduced a new magnetic resonance imaging (MRI) technique known as the Cr-amine
chemical exchange saturation transfer (CrCEST), which measures free Cr formed from PCr utilization. CrCEST
provides over three orders of magnitude higher sensitivity compared to 31P-MRS and can also be used to
investigate CK kinetics and muscle bioenergetics.
In this proposal, we further develop and optimize the CrCEST for use in humans, by improving time resolution,
characterizing reproducibility, and assessing the effects of pH. As a critical part of interrogating the optimized
CrCEST technique, we will test the effects of age, sex, race and physical activity on high-resolution CrCEST in
healthy adults. We expect to demonstrate muscle group specific differences in creatine metabolism and
OXPHOS capacity using non-invasive techniques that were not feasible until now.
Successful accomplishment of this project will i) yield quantitative imaging biomarkers of muscle creatine
metabolism, lactate metabolism and OXPHOS capacity that provide anatomic specificity without the
invasiveness of biopsy-based approaches; ii) provide reference data to support future studies using CrCEST
signal as a non-invasive index of muscle quality in aging and other conditions, including but not limited to
diabetes, muscular dystrophy, peripheral arterial disease, and genetic mitochondrial disorders. We anticipate
that CrCEST (iii) will also serve as a non-invasive muscle group specific monitoring tool to evaluate response to
potential therapies targeting abnormal muscle metabolism in aging, in neuromuscular disorders, and myriad
other conditions. Thus, CrCEST based technologies have the potentia...

## Key facts

- **NIH application ID:** 10364987
- **Project number:** 1R01AG071725-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Ravinder Reddy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $644,539
- **Award type:** 1
- **Project period:** 2022-02-01 → 2026-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364987

## Citation

> US National Institutes of Health, RePORTER application 10364987, In vivo Mapping of Muscle Specific Metabolism (1R01AG071725-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10364987. Licensed CC0.

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