# Hyperpolarized 13C Metabolic MRI for Noninvasive Monitoring of Kidney Injury

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $242,250

## Abstract

The overarching goal of this project is to develop a kidney metabolic imaging tool based on
hyperpolarized (HP) 13C pyruvate MRI to investigate kidney energy metabolism for noninvasive
monitoring of human kidney injury. This is in response to PAR-20-140: Catalytic Tool and Technology
Development in Kidney, Urologic, and Hematologic Diseases encouraging “innovative radiological
or intravital imaging methods, or novel imaging probes for study of the kidney”. The kidney is a highly
energy-dependent organ requiring mitochondrial oxidative metabolism for key renal functions. Increasing
evidence indicates that a shift from pyruvate mitochondrial oxidative phosphorylation to glycolysis and
lactate production plays a central role in many etiologies of kidney injury leading to chronic kidney
disease, which represents a major public health problem in the United States. Notably, currently available
clinical tests such as serum creatine are known to be insensitive for monitoring kidney injury, and better
noninvasive tools are needed. HP 13C MRI is an innovative technology platform that provides
unprecedented gains in sensitivity (>10,000-fold signal increase) for imaging 13C-labeled bio-molecules,
thereby permitting rapid and noninvasive investigation of dynamic metabolic processes. We have shown
in a murine model of kidney ischemia-reperfusion injury that HP 13C pyruvate MRI can monitor the
impaired mitochondrial pyruvate dehydrogenase (PDH) activity and the shift from oxidative metabolism
to glycolysis in injured kidneys. Importantly, HP 13C pyruvate as a contrast agent has already been shown
to be safe in initial cancer patient studies. However, human kidney studies with this approach require
kidney-specific technology development. We propose to develop imaging tools to enable increased
sensitivity to multiple metabolic pathways including PDH-mediated conversion to bicarbonate that is
limited in signal with current methods, to ensure reproducibility, and to address issues of high perfusion
unique to the kidneys for metabolism quantification. For an initial demonstration study, we propose to
image patients with kidney allograft in order to correlate HP 13C pyruvate MRI with histopathology from
biopsies; this will enable understanding of the molecular underpinning of the imaging findings that will be
important for developing future studies in various kidney diseases. This enabling technology has an
outstanding potential to advance our understanding of energy metabolism in kidney disease, to improve
its timely diagnosis and therapy monitoring for both clinical research and clinical care. The tools from this
technology development project can be readily disseminated to other sites, allowing broader adoption of
the technology for studying kidney disease.

## Key facts

- **NIH application ID:** 10449286
- **Project number:** 5R21DK130002-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Peder Eric Zufall Larson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $242,250
- **Award type:** 5
- **Project period:** 2021-07-12 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10449286

## Citation

> US National Institutes of Health, RePORTER application 10449286, Hyperpolarized 13C Metabolic MRI for Noninvasive Monitoring of Kidney Injury (5R21DK130002-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10449286. Licensed CC0.

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