# Hyperpolarized 13C MRI of renal mitochondrial dysfunction

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2022 · $196,875

## Abstract

PROJECT SUMMARY
Mitochondrial dysfunction is recognized as a key early driver for disease progression in diabetic nephropathy
(DN), among other chronic diseases, yet there exist very few tools for non-invasive assessment of mitochondrial
status. Given that DN is an important source of diabetes-related morbidity and mortality (through its impact on
cardiovascular outcomes), the ability to better understand and potentially even predict the progression of patients
with diabetes to DN could have a large impact on clinical management of diabetes. The purpose of this R21
proposal (“Catalytic Tool and Technology Development in Kidney, Urologic, and Hematologic Diseases”) is to
develop a new imaging probe with mitochondria-specific reactivity for hyperpolarized (HP) 13C MRI, [1,3-
13C2]acetoacetate (AcAc), providing non-invasive readout of mitochondrial metabolic status. This mitochondria-
targeted ketone body probe has several favorable features with respect to HP 13C technology including long T1
signal lifetime, low toxicity, and rapid cellular uptake, but also has major associated challenges which have
hampered development. To address these, we propose several technical innovations including: 1) improved
chemical synthesis with increased purity and stability, 2) first-ever hyperpolarization on the state-of-the-art
human-scale GE SPINlab 5T instrument, 3) improved formulation for dynamic nuclear polarization (DNP) with
potentially higher polarization levels and shorter buildup times, and 4) highly efficient data acquisition with a
novel pulse sequence employing multi-band spectral-spatial radiofrequency (SSRF) pulse excitation on a new
MR/PET preclinical imaging platform (MR Solutions). The cumulative impact of these innovations is expected to
provide a sensitivity gain of more than an order of magnitude over recent limited “proof of concept” work,
propelling HP [1,3-13C2]AcAc into a powerful new imaging-based tool for assessing mitochondrial health.
The tool will be evaluated in a well-characterized rodent model of DN, to directly test the hypothesis that HP [1-
13C]AcAc can detect early DN prior to clinically detectable manifestations. Lastly, consistent with the FOA, we
are committed to a clear plan for sharing the newly developed “Catalytic Tool” with potential users (>30 labs with
the necessary equipment for HP 13C MRI), including sharing all protocols for chemical synthesis and formulation,
as well as sharing all pulse sequence source code, novel SSRF pulse waveforms, and data from the study online.

## Key facts

- **NIH application ID:** 10593424
- **Project number:** 1R21DK131358-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Cornelius von Morze
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $196,875
- **Award type:** 1
- **Project period:** 2022-09-21 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10593424

## Citation

> US National Institutes of Health, RePORTER application 10593424, Hyperpolarized 13C MRI of renal mitochondrial dysfunction (1R21DK131358-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10593424. Licensed CC0.

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