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Abstract #4653

Evaluating hepatic metabolic derangements in a diet and oxidative stress induced mouse model of MASLD with hyperpolarized [1-13C]-pyruvate

Andrew Cho1, Sung-Han Lin2, Melissa Inigo-Volmer3, Monika Mizerska3, Morgan Villegas3, Suntrea Hammer4, Xiaodong Wen2, Nicholas Browder3, Zohreh Erfani5, Jae Mo Park1,2,6, Craig Malloy1,2,7, and Shawn Burgess3,8
1Radiology, University of Texas Southwestern Medical Center, Dallas, TX, United States, 2Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, United States, 3Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, United States, 4Pathology, University of Texas Southwestern Medical Center, Dallas, TX, United States, 5University of Texas Southwestern Medical Center, Dallas, TX, United States, 6Biomedical Engineering, University of Texas Southwestern Medical Center, Dallas, TX, United States, 7Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States, 8Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, United States

Synopsis

Keywords: Hyperpolarized MR (Non-Gas), Hyperpolarized MR (Non-Gas), MASLD, MASH, Steatotic Liver Disease

Motivation: Clinical management of metabolic dysfunction-associated steatotic liver disease (MASLD) is hindered by the absence of non-invasive tests to longitudinally monitor disease progression and treatment response.

Goal(s): Evaluate if hyperpolarized (HP) [1-13C]-pyruvate MRS can distinguish different grades of steatotic liver injury.

Approach: In a mouse model of MASLD, ex vivo metabolite analysis was performed to characterized perturbations in pyruvate metabolism associated with disease progression. This was used to guide interpretation of in vivo HP MRS.

Results: Ex vivo analysis demonstrates decreasing pyruvate dehydrogenase (PDH) flux relative to pyruvate carboxylase throughout disease progression. HP MRS demonstrates decreased PDH flux in early MASLD relative to control.

Impact: Our results demonstrate that HP [1-13C]-pyruvate is a promising molecular imaging probe for the non-invasive diagnosis of simple steatosis/MASH and potentially offers a safe alternative to liver biopsy that is more appropriate for longitudinal disease monitoring.

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Abstract

Keywords