A CT technique to evaluate the development of carcinogen-induced neoplasia in the rat liver

Hepatocellular neoplasms, including neoplastic nodules (NN), are the most commonly induced tumors resulting from chemical carcinogen evaluation. Our objective was to image neoplastic nodules using computed tomography. In a preliminary study using rats with diethylnitrosamine (DEN) induced tumors, lesions smaller than 1.5 cm were difficult to identify by CT. Since NN do not take up excess iron whereas normal liver does accumulate iron, we studied iron as a CT contrast material. Hemochromatosis was induced in 15 control rats by subcutaneous injections of iron dextran. A linear increase in iron-loading dose produces a linear CT liver enhancement (r = 0.97): 68, 80, 84, 94, and 104 HU at 0, one, two, four, and six weeks, respectively. No loss of enhancement was noted ten weeks later. Rat hepatic tissue was chemically analyzed after a similar iron-loading regimen. The iron concentration (microgram/g hepatic tissue) progressively increased during the first four weeks of loading and remained stable for three weeks following iron-loading. Four animals that had been given DEN and iron were examined by CT scanning to detect small NN. Iron-enhanced CT allowed the visualization of small lesions (less than 5 mm). Histopathologic sections confirmed a homogeneous pattern of iron uptake in normal liver with a deficiency of iron in NN. We conclude that CT scanning following iron-loading is a noninvasive method to detect small nodules and may provide a method to study the progression or regression of small liver nodules in rodents.