Monitoring the development of hepatocellular carcinoma in woodchucks using 31P-MRS

Abstract

The woodchuck is one of the only lab animal models of chronic viral hepatitis infection and the development of hepatocellular carcinoma. Using this model, changes in tissue energetics in the liver due to the development of hepatocellular carcinoma can be monitored by repeated magnetic resonance imaging and localized phosphorus spectroscopy. Age- and sex-matched control (n=5) and chronically infected (n=5) adult woodchucks were imaged four times in a six-month period in a 7-T horizontal-bore magnet. Using a custom-built doubly tunable quadrature volume coil, sagittal and axial FLASH images (128 x 128, slice thickness = 5 mm, TR/TE=1000/4.1, 8 averages) were acquired to locate the largest portion of the liver with the least amount of signal contamination from surrounding abdominal muscle. Two-dimensional 31P chemical-shift imaging (2D-CSI) was acquired (16 x 16 data matrix, 24 x 24 x 2 cm3, 1024 data points, 16 averages) for all animals. The extent of liver injury was determined using serum gamma glutamyltransferase (GGT). The livers of infected woodchucks showed a significant increase (p=0.01) in phosphomonoesters (PME):beta-adenosine triphosphate (NTP). Chronically infected woodchucks had higher levels of serum GGT compared to uninfected woodchucks (p=0.002). An increase in the PME:beta-NTP ratio indicates cellular proliferation within the malignant tumor.