Differentiation of reactive and tumor metastatic lymph nodes with diffusion-weighted and superparamagnetic iron oxide enhanced MRI

Objectives Determination of lymphatic metastases is of great importance for both treatment planning and patient prognosis. We aim to distinguish tumor metastatic lymph nodes and reactive lymph nodes with diffusion weighted and superparamagnetic iron oxide enhanced magnetic resonance imaging (MRI).

Methods Ipsilateral popliteal lymph node metastases or lymphadenitis were developed by hock injection of either luciferase-expressing murine breast cancer 4T1 cells or Complete Freund Adjuvant (CFA) in male Balb/C mice. At different time points after inoculation, bioluminescent imaging, T2-weighted, diffusion weighted and iron oxide enhanced MRI were performed using an IVIS system and a 7T MRI scanner. Imaging findings were confirmed by histopathologic staining.

Results Size enlargement was observed in both tumor draining lymph nodes (TLNs) and reactive lymph nodes (RLNs). At day 28, TLNs showed strong BLI signal and much bigger size than RLNs (p < 0.01). At early stage up to day 21, tumor draining and reactive LNs appeared homogeneous on DW MRI. At day 28, TLNs showed heterogeneous ADC map with significant higher average ADC value of 0.41 ± 0.03 x10^-3 mm²/s (p< 0.05). On supermagnetic iron oxide enhanced MRI, both TLNs and RLNs showed distinct T2 signal reduction at day 21 after inoculation. At day 28, TLNs demonstrated partial uptake of the iron oxide particles, which is confirmed by Prussian blue staining.

Conclusions Both diffusion-weighted and SPIO enhanced MRI can distinguish tumor metastatic lymph nodes with reactive lymph nodes. However, both methods failed to tell the difference between tumor draining LNs and reactive LNs at early stage of tumor metastasis.

Research Support Intramural Research Program, NIBIB, NI