PURPOSE: The purpose of this experimental study was to determine the optimal pulse sequences for SPIO-enhanced MR imaging in the evaluation of multiple hepatic tumors. MATERIALS AND METHODS: Twelve rabbits with multiple VX2 liver tumors underwent SPIO-enhanced MRI using the following nine pulse sequences: TSE T2-weighted imaging (T2WI), TSE proton density-weighted imaging (PDWI), and GRE T2*-weighted imaging (T2*WI) with seven different echo times (TE). Liver-lesion contrastto-noise ratios (CNRs) were calculated, and images were also assessed qualitatively by two radiologists, who reached a consensus as to lesion conspicuity and imaging artefacts using a four-level scale. By means of pathologic correlation, the sensitivity and positive predictive value of each sequence was calculated. RESULTS: TSE T2WI and long-TE (35 msec) FLASH T2*WI showed the highest liver-lesion CNR. The best lesion conspicuity was seen at TSE T2WI and medium-TE (12 msec) GRE T2*WI. Short TE GRE T2*WI showed the least imaging artefacts. The four sequences which demonstrated the best sensitivity were medium-TE (12 msec), GRE T2*WI (FLASH, 84%; FISP, 82%), TSE T2WI (79%), and TSE PDWI (76%). All nine sequences showed overall high positive predictive value (86-97%), with no statistically significant difference (p>0.05). CONCLUSION: In terms of image quality and the detection of sensitivity, TSE T2WI and medium TE (12 msec) GRE T2*WI were the top two pulse sequences among the various sequences used for on SPIO-enhanced MRI. They are thus considered to be the optimal sequences for evaluating multiple malignant hepatic tumors.