Differentiation of Reactive and Tumor Metastatic Lymph Nodes with Diffusion-weighted and SPIO-Enhanced MRI

Determination of lymphatic metastasis is of great importance for both treatment planning and patient prognosis. We aim to distinguish tumor metastatic lymph nodes (TLNs) and reactive lymph nodes (RLNs) with diffusion-weighted and superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI). Ipsilateral popliteal lymph node metastasis or lymphadenitis model was established by hock injection of either luciferase-expressing 4T1 murine breast cancer cells or complete Freund's adjuvant in male BALB/c mice. At different time points after inoculation, bioluminescence imaging and T-2-weighted, diffusion-weighted, and SPIO-enhanced MRI were performed. Imaging findings were confirmed by histopathological staining. Size enlargement was observed in both TLNs and RLNs. At day 28, TLNs showed strong bioluminescence signal and bigger size than RLNs (p < 0.01). At early stages up to day 21, both TLNs and RLNs appeared homogeneous on diffusion-weighted imaging. At day 28, TLNs showed heterogeneous apparent diffusion coefficient (ADC) map with significantly higher average ADC value of 0.41 +/- 0.03 x 10(-3)mm(2)/s than that of RLNs (0.34 +/- 0.02 x 10(-3)mm(2)/s; p < 0.05). On SPIO-enhanced MRI, both TLNs and RLNs showed distinct T-2 signal reduction at day 21 after inoculation. At day 28, TLNs demonstrated partial uptake of the iron oxide particles, which was confirmed by Prussian blue staining. Both diffusion-weighted and SPIO-enhanced MRI can distinguish tumor metastatic lymph nodes from reactive lymph nodes. However, neither method is able to detect tumor metastasis to the draining lymph nodes at early stages.