Development of hepatomas in hyperplastic nodules induced in the rat liver: detection with superparamagnetic iron oxide-enhanced magnetic resonance imaging

Abstract

Rationale and objectives: Hyperplastic nodules developed in cirrhotic livers reportedly show accumulations of superparamagnetic iron oxide (SPIO) on magnetic resonance (MR) images, whereas hepatocellular carcinomas do not. We examined whether SPIO-enhanced MR imaging would detect cancerous liver lesions within hyperplastic nodules.

Methods: The study included 40 rats with N-2-fluorenyldiacetamide (FAA)-induced liver tumors. Spin-echo T1-, T2-, and proton density-weighted images were obtained at 1.5 T before and after the administration of SPIO. We evaluated 47 tumors accumulating iron particles on SPIO-enhanced MR images. Among the 47 tumors, 33 were observed on MR images obtained 10-26 weeks after the initiation of the carcinogenic diet. The signal intensity changes within the tumors were observed at 2 weeks and were compared with histologic findings. As a control study, 30 hyperintense (non-SPIO-enhanced) tumors also received pathologic examination.

Results: Hyperintense (non-SPIO-enhanced) foci within hypointense (SPIO-enhanced) tumors were observed in seven of the 33 tumors on all pulse sequences, and hyperintense (non-SPIO-enhanced), enlarged foci were observed in three of the seven lesions. In the remaining 26 lesions, the signal intensity of the tumor was totally hypointense on all pulse sequences at initial and follow-up MR imaging. During the 2-week follow-up period, 15 hypointense (SPIO-enhanced) tumors were replaced by hyperintense (non-SPIO-enhanced) tumors. Histologically, SPIO-accumulating tumors were hyperplastic nodules; the lesions that did not accumulate SPIO were hepatocellular carcinomas or hyperplastic nodules with atypical cells.

Conclusion: MR imaging using SPIO detects the development of hepatocellular carcinoma at an early stage in our animal model.