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In Vivo Magnetic Resonance Spectroscopy of Hyperpolarized [ 1‐ 13 C ]Pyruvate and Proton Density Fat Fraction in a Guinea Pig Model of Non‐Alcoholic Fatty Liver Disease Development After Life‐Long Western Diet Consumption
Author(s) -
Smith Lauren M.,
Pitts Conrad B.,
FriesenWaldner Lanette J.,
Prabhu Neetin H.,
Mathers Katherine E.,
Sinclair Kevin J.,
Wade Trevor P.,
Regnault Timothy R.H.,
McKenzie Charles A.
Publication year - 2021
Publication title -
journal of magnetic resonance imaging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.563
H-Index - 160
eISSN - 1522-2586
pISSN - 1053-1807
DOI - 10.1002/jmri.27677
Subject(s) - fatty liver , in vivo , choline , ex vivo , medicine , metabolite , triglyceride , chemistry , lactate dehydrogenase , endocrinology , in vivo magnetic resonance spectroscopy , fatty acid , nuclear magnetic resonance , magnetic resonance imaging , cholesterol , biology , biochemistry , enzyme , disease , physics , microbiology and biotechnology , radiology
Background Alterations in glycolysis are central to the increasing incidence of non‐alcoholic fatty liver disease (NAFLD), highlighting a need for in vivo, non‐invasive technologies to understand the development of hepatic metabolic aberrations. Purpose To use hyperpolarized magnetic resonance spectroscopy (MRS) and proton density fat fraction (PDFF) magnetic resonance imaging (MRI) techniques to investigate the effects of a chronic, life‐long exposure to the Western diet (WD) in an animal model resulting in NAFLD; to investigate the hypothesis that exposure to the WD will result in NAFLD in association with altered pyruvate metabolism. Study Type Prospective. Animal Model Twenty‐eight male guinea pigs weaned onto a control diet ( N = 14) or WD ( N = 14). Field Strength/Sequence 3 T; T1‐weighted gradient echo, T2‐weighted spin‐echo, three‐dimensional gradient multi‐echo fat‐water separation (IDEAL‐IQ), and broadband point‐resolved spectroscopy (PRESS) chemical‐shift sequences. Assessment Median PDFF was calculated in the liver and hind limbs. [1‐ 13 C]pyruvate dynamic MRS in the liver was quantified by the time‐to‐peak (TTP) for each metabolite. Animals were euthanized and tissue was analyzed for lipid and cholesterol concentration and enzyme level and activity. Statistical Tests Unpaired Student's t ‐tests were used to determine differences in measurements between the two diet groups. The Pearson correlation coefficient was calculated to determine correlations between measurements. Results Life‐long WD consumption resulted in significantly higher liver PDFF and elevated triglyceride content in the liver. The WD group exhibited a decreased TTP for lactate production, and ex vivo analysis highlighted increased liver lactate dehydrogenase (LDH) activity. Data Conclusion PDFF MRI results suggest differential fat deposition patterns occurring in animals fed a life‐long WD characteristic of lean, or lacking excessive subcutaneous fat, NAFLD. The decreased liver lactate TTP and increased ex vivo LDH activity suggest lipid accumulation occurs in association with a shift from oxidative metabolism to anaerobic glycolytic metabolism in WD‐exposed livers. Level of Evidence 2 Technical Efficacy Stage 1