Assessing inflammatory liver injury in an acute CCl4 model using dynamic 3D metabolic imaging of hyperpolarized 1-13Cpyruvate

摘要

To facilitate diagnosis and staging of liver disease, sensitive and non-invasive methods for the measurement of liver metabolism are needed. This study used hyperpolarized ¹³C-pyruvate to assess metabolic parameters in a CCl4-model of liver damage in rats. Dynamic 3D ¹³C CSI data from a volume covering kidney and liver were acquired from 8 control and 10 CCl4-treated rats. In 12 time points at 5-s temporal resolution, we quantified the signal intensities and established time courses for pyruvate, alanine and lactate. Those measurements were compared to standard liver histology and an alanine transaminase (ALT) enzyme assay using liver tissue from the same animals. All CCl4-treated, but none of the control animals showed histological liver damage and elevated ALT enzyme levels. In agreement with those results, metabolic imaging revealed an increased alanine-to-pyruvate ratio in liver of CCl4-treated rats, which is indicative of elevated ALT activity. Similarly, lactate/pyruvate ratios were higher in CCl4-treated compared to control animals, demonstrating the presence of inflammation. No significant differences in metabolite ratios were observed in kidney or vasculature. Thus this work shows that metabolic imaging using ¹³C-pyruvate can be a successful tool to non-invasively assess liver damage in vivo.