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Objective: To investigate the potential of superparamagnetic iron oxide particles (SPIO) in MR imaging for the differentiation between hyperplastic and metastatic lymph node. Methods: Animal models of malignant lymph node metastasis were established in 6 New-Zealand rabbits by a unilateral intra-muscular injection of VX2 carcinoma cells, and models of hyperplastic lymph nodes were induced in another 6 rabbits by a unilateral intra-muscular injection of egg yolk emulsion. MR images of the lymph nodes were obtained before and 12 h after interstitial injection of SPIO. Image results were analyzed and compared with pathological findings. Results: On unenhanced images, the signal intensity of hyperplastic and metastatic lymph nodes did not differ significantly. After administration of SPIO, the signal intensity of both hyperplastic and metastatic lymph nodes remained unchanged on T1-weighted SE images. On T2-weighted SE images, the signal intensity of hyperplastic lymph nodes decreased heterogeneously, while that of all metastatic ones remained unchanged. On T2-weighted GRE images, the signal intensity of hyperplastic lymph nodes decreased significantly and homogeneously, while that of 4 metastatic ones remained unchanged and that of the rest 2 decreased heterogeneously. Conclusion: SPIO-enhanced MR imaging may enable the differentiation between the hyperplastic and metastatic lymph nodes.