# Novel hyperpolarized 13C molecular imaging techniques for differentiating NAFLD and NASH

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $415,502

## Abstract

PROJECT SUMMARY / ABSTRACT
Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition characterized by ectopic hepatic lipid
accumulation in association with obesity and type 2 diabetes. A progressive derangement of hepatic energy
metabolism underlies the progression of simple fatty liver to non-alcoholic steatohepatitis (NASH), a condition
that carries high risk for progression to critical liver disease states. Unfortunately, the current method for
monitoring NAFLD is liver biopsy, which has major limitations especially its high degree of invasiveness.
Hyperpolarized 13C magnetic resonance imaging (MRI) is an emerging molecular imaging modality with a
unique capability to access intermediary energy metabolism in a non-invasive manner, which is currently
undergoing translation into human studies at several sites internationally in studies of cancer and
cardiovascular disease. The goal of this new R01 project is to investigate a new application of this new
molecular imaging modality to the assessment of NAFLD.
The association between detected changes in hyperpolarized 13C MRI and progression of NAFLD will first be
investigated in a preclinical model of the progression of NAFLD to NASH (Aim 1), specifically Zucker diabetic
fatty (ZDF) rats fed a high fat diet. Two promising hyperpolarized probes of hepatic energy metabolism, [1-
13C]pyruvate and [2-13C]dihydroxyacetone, will be applied to these studies. These new hyperpolarized markers
will be compared against gold standard measures of NAFLD derived from pathology, as well as biochemical
assays of hepatic energy state and oxidative stress. Next, novel MRI methods will be developed to enable
clinical translation of hyperpolarized 13C imaging of the liver (Aim 2). The proposed approach aims to enable
dynamic free-breathing imaging of the entire liver by accelerated echo planar imaging (EPI) acquisition with
sixteen-channel parallel imaging. To address the key challenge of array sensitivity calibration, a highly novel
approach to parallel imaging will be deployed based on continuous tracking of receiver coil positions using an
integrated manganese-55 MRI based fiducial marker system. Finally, initial clinical hyperpolarized [1-
13C]pyruvate MRI will be performed in normal subjects and patients with simple steatosis and NASH, with
comparison to liver biopsy (Aim 3).
By the end of this new five-year R01 Research Project Grant, we aim to deliver a valuable new clinical tool for
non-invasively assessing the progression of NAFLD based on associated metabolic changes measured using
hyperpolarized 13C MRI.

## Key facts

- **NIH application ID:** 10240628
- **Project number:** 5R01DK115987-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Michael Ohliger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $415,502
- **Award type:** 5
- **Project period:** 2018-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10240628

## Citation

> US National Institutes of Health, RePORTER application 10240628, Novel hyperpolarized 13C molecular imaging techniques for differentiating NAFLD and NASH (5R01DK115987-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10240628. Licensed CC0.

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