Chronic care and monitoring of woodchucks (Marmota monax) during repeated magnetic resonance imaging of the liver.

ABSTRACT

We monitored the development of hepatocellular carcinoma due to chronic infection with woodchuck hepatitis virus by using monthly serum samples, physical examination, and magnetic resonance imaging. The same woodchucks can be imaged repeatedly over a 1-y period by allowing the animals to recover after each experiment, thus reducing the number of animals required without compromising the quality of the data obtained. Age- and sex-matched uninfected control (n = 5) and chronically infected (n = 5) woodchucks were group-housed according to sex and infection status. Woodchucks were anaesthetized using an inhalation anesthetic (isoflurane) without premedication. During imaging, we regularly monitored heart rate, body temperature, and respiration. Tumor growth was observed using MRI, whereas the extent of hepatocyte injury was followed using serum liver enzymes. Elevated serum gamma glutamyltransferase and aspartate aminotransferase levels indicated hepatocyte injury due to tumor growth. On magnetic resonance images, the liver should appear as a well-defined, homogenous organ with defined regions of hyperintensities from larger blood vessels. Within tumor nodules, the liver appeared irregularly shaped, having heterogeneous intensity from unregulated cellular proliferation. Changes in tumor size can be monitored by imaging infected woodchucks on a regular basis. Using the imaging techniques we describe, the development of hepatocellular carcinoma can be visualized using magnetic resonance imaging, correlated to serum tests, and compared with the results from uninfected control woodchucks, thereby improving the understanding of the disease progress.