Hyperpolarized [1-13C] pyruvate MRSI to detect metabolic changes in liver in a methionine and choline-deficient diet rat model of fatty liver disease
Joao Piraquive Agudelo, Yaewon Kim, Shubhangi Agarwal, Renuka Sriram, Robert Bok, John Kurhanewicz, Aras N. Mattis, Jacquelyn J. Maher, Cornelius von Morze, Michael A. Ohliger
Abstract
Purpose
Nonalcoholic fatty liver disease is an important cause of chronic liver disease. There are limited methods for monitoring metabolic changes during progression to steatohepatitis. Hyperpolarized 13C MRSI (HP 13C MRSI) was used to measure metabolic changes in a rodent model of fatty liver disease.
Methods
Fifteen Wistar rats were placed on a methionine- and choline-deficient (MCD) diet for 1–18 weeks. HP 13C MRSI, T2-weighted imaging, and fat-fraction measurements were obtained at 3 T. Serum aspartate aminotransaminase, alanine aminotransaminase, and triglycerides were measured. Animals were sacrificed for histology and measurement of tissue lactate dehydrogenase (LDH) activity.
Results
Animals lost significant weight (13.6% ± 2.34%), an expected characteristic of the MCD diet. Steatosis, inflammation, and mild fibrosis were observed. Liver fat fraction was 31.7% ± 4.5% after 4 weeks and 22.2% ± 4.3% after 9 weeks. Lactate-to-pyruvate and alanine-to-pyruvate ratios decreased significantly over the study course; were negatively correlated with aspartate aminotransaminase and alanine aminotransaminase (r = −[0.39–0.61]); and were positively correlated with triglycerides (r = 0.59–0.60). Despite observed decreases in hyperpolarized lactate signal, LDH activity increased by a factor of 3 in MCD diet–fed animals. Observed decreases in lactate and alanine hyperpolarized signals on the MCD diet stand in contrast to other studies of liver injury, where lactate and alanine increased. Observed hyperpolarized metabolite changes were not explained by alterations in LDH activity, suggesting that changes may reflect co-factor depletion known to occur as a result of oxidative stress in the MCD diet.
Conclusion
HP 13C MRSI can noninvasively measure metabolic changes in the MCD model of chronic liver disease.