# Mapping Functional Heterogeneity in Tissue

> **NIH NIH R21** · NORTH CAROLINA STATE UNIVERSITY RALEIGH · 2020 · $182,542

## Abstract

ABSTRACT
Abstract: Mass spectrometry imaging (MSI) provides unprecedented detail of molecular distributions across ex
vivo tissue samples. Although MSI has the capability to map molecules ranging from large proteins to small
metabolites, these data only describe the tissue status at a single time point and lack any information on how
these molecules interact to provide metabolic function. Typical functional studies derive kinetic data from
administration of isotope-labeled substrates and monitoring label transit in tissue samples harvested over a
specified time-course. Isotope kinetics tracked by MSI, however, have some unique requirements to in order to
perform a similar functional study and exploit the full power of the technique to provide location-specific
metabolite flux. This proposal will develop an MSI-based method to track isotope metabolic activity through the
use of a timed infusion of isotopologues of glycine to measure the rate of glutathione and serine metabolic flux
within each 50 x 50 x 10 m image voxel. This timed infusion allows a voxel-by-voxel determinations of metabolic
rates, i.e. functional images that are not possible by other methods. In addition, since metabolic flux and pathway
selection is influenced both by tissue perfusion and oxygenation, we also will develop MSI-based methods to
measure tissue perfusion and hypoxia in the same samples. Isotopologues of pimonidazole will be used to map
regions of both chronic and cycling hypoxia that can be tied directly to glutathione metabolic activity. To
demonstrate the feasibility of these techniques in different tissue types, we will map functional heterogeneity
across mouse liver and mammary 4T1 tumors. As the MSI method uses frozen thin-sections, histochemical data
from adjacent sections can be used to tie traditional tissue markers to metabolic function. The methods described
herein will be demonstrated on the glutathione and serine pathways but can be used to study functional
heterogeneity in any tissue and any metabolic network with proper selection of substrates.

## Key facts

- **NIH application ID:** 10018055
- **Project number:** 5R21GM134219-02
- **Recipient organization:** NORTH CAROLINA STATE UNIVERSITY RALEIGH
- **Principal Investigator:** MICHAEL GAMCSIK
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $182,542
- **Award type:** 5
- **Project period:** 2019-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018055

## Citation

> US National Institutes of Health, RePORTER application 10018055, Mapping Functional Heterogeneity in Tissue (5R21GM134219-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10018055. Licensed CC0.

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