# Hyperpolarized 13C metabolic imaging in an endovascular swine model of ischemic stroke

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $231,750

## Abstract

Ischemic stroke (IS) is the most frequent cause of long-term severe disability, and places an enormous eco-
nomic burden on society. One of the primary goals in clinical care of acute stroke is to salvage the so-called
penumbra, i.e., tissue that is at risk of irreversible infarction, but is still viable. This can be achieved through
various strategies that re-establish the perfusion of the affected tissue. However, there is a tight time window for
intervention as well as a risk of cerebral hemorrhage during the establishment of reperfusion and it requires an
accurate assessment of the extend of injury as benefits from reperfusion have to be weighed against potential
complications arising from treatment. The most widely used tool in identifying the penumbra is magnetic
resonance imaging (MRI) and exploiting the “mismatch” in abnormalities as measured with perfusion-weighted
and diffusion-weighted MRI. However, multiple studies have found that these surrogate markers have
mischaracterized irreversibly infarcted and salvageable tissue and the inaccuracy of these markers may have
contributed to both inconclusive results from clinical trials and negative therapeutic outcomes. To this end, a
more accurate identification of penumbra and ischemic core that could expand the patient pool that benefit from
treatment is needed.
 The reduced delivery of oxygen and glucose following IS leads to impaired energy metabolism within the
affected tissue, one of the hallmarks of the pathology. Therefore, new approaches for quantitative and spatially
precise assessment of brain energy metabolism could lead to improved assessment of injury following IS. The
recent development of hyperpolarized 13C magnetic resonance spectroscopy and spectroscopic imaging enables
for the first time the real-time non-invasive measurement of critical dynamic metabolic processes in vivo. Given
pyruvate’s central role in energy metabolism as the link between glycolysis and the Krebs cycle, we propose to
use metabolic imaging of co-polarized pyruvate (Pyr) and urea for noninvasive assessment of brain energy
metabolism and perfusion in a novel swine IS model. Specifically, we will use injections of co-polarized [1-13C]Pyr
and [13C,15N2]urea to quantify cellular energy metabolism and brain perfusion at the time of IS completion in order
to identify regions of ischemic core, penumbra, and healthy tissue using histology as the gold standard (Aim 1).
Secondly, we will expand our study to include multiple time points during stroke evolution as well as after
reperfusion. This will further characterize the temporal and spatial extent of metabolic changes in IS and allow
the comparison with the time course of abnormalities as measured with diffusion-weighted MRI (Aim 2).
 The proposed combination of a novel endovascular swine model of IS and metabolic imaging of
hyperpolarized substrates is a unique model system to study the pathophysiology of IS and develop new
treatments prior to clinical trials. ...

## Key facts

- **NIH application ID:** 10932974
- **Project number:** 5R21NS133531-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Miroslaw Janowski
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $231,750
- **Award type:** 5
- **Project period:** 2023-09-21 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10932974

## Citation

> US National Institutes of Health, RePORTER application 10932974, Hyperpolarized 13C metabolic imaging in an endovascular swine model of ischemic stroke (5R21NS133531-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10932974. Licensed CC0.

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