Open AccessDifferentiation of Heterogeneous Mouse Liver from HCC by Hyperpolarized 13C Magnetic Resonance
Author(s) -
Naama LevCohain,
Gal Sapir,
Sivaranjan Uppala,
Atara NardiSchreiber,
S. Nahum Goldberg,
Yael AdlerLevy,
Jacob Sosna,
John M. Gomori,
Rachel KatzBrull
Publication year - 2020
Publication title -
sci
Language(s) - English
Resource type - Journals
ISSN - 2413-4155
DOI - 10.3390/sci2020043
Subject(s) - hepatocellular carcinoma , lactate dehydrogenase , magnetic resonance imaging , alanine transaminase , liver disease , aspartate transaminase , pathology , liver biopsy , medicine , in vivo , biopsy , chemistry , cancer research , biology , enzyme , biochemistry , alkaline phosphatase , radiology , microbiology and biotechnology
The clinical characterization of small hepatocellular carcinoma (HCC) lesions in the liver and differentiation from heterogeneous inflammatory or fibrotic background is important for early detection and treatment. Metabolic monitoring of hyperpolarized 13C-labeled substrates has been suggested as a new avenue for diagnostic magnetic resonance. The metabolism of hyperpolarized [1-13C]pyruvate was monitored in mouse precision-cut liver slices (PCLS) of aged MDR2-KO mice, which served as a model for heterogeneous liver and HCC that develops similarly to the human disease. The relative in-cell activities of lactate dehydrogenase (LDH) to alanine transaminase (ALT) were found to be 0.40 ± 0.06 (n = 3) in healthy livers (from healthy mice), 0.90 ± 0.27 (n = 3) in heterogeneously inflamed liver, and 1.84 ± 0.46 (n = 3) in HCC. Thus, the in-cell LDH/ALT activities ratio was found to correlate with the progression of the disease. The results suggest that the LDH/ALT activities ratio may be useful in the assessment of liver disease. Because the technology used here is translational to both small liver samples that may be obtained from image-guided biopsy (i.e., ex vivo investigation) and to the intact liver (i.e., in a non-invasive MRI scan), these results may provide a path for differentiating heterogeneous liver from HCC in human subjects.