Purpose: We investigated the spatiotemporal changes in signal in draining lymph nodes of mice to ascertain the size-dependent effects of variously sized particles of iron oxide used to enhance magnetic resonance (MR) lymphography.
Materials and Methods: We injected iron oxide particles of 50-, 100-, 200-, or 1,000-nm diameter into the footpads of individual mice and obtained sequential MR images of the popliteal and inguinal lymph nodes with 11.7 tesla up to 6 weeks after particle administration.
Results: Up to 30 min after administration of particles smaller than 100 nm, we observed a marked reduction in signal in the popliteal node that spread from the periphery at first observation toward the center of the node in subsequent measurements and persisted up to 6 weeks. In contrast, 1,000-nm particles caused dot-like areas of hypointensity in the popliteal lymph node, primarily in the inner portion, that appeared after 2 days. In the inguinal lymph nodes, signal changes occurred after 2 days for 50- and 100-nm particles and after one week for 1,000-nm particles. For 1,000-nm particles, areas of hypointensity were visible in the inner portion and not the periphery of the inguinal lymph node up to 6 weeks. In this study, we demonstrate the strong dependence of MR imaging contrast in draining lymph nodes on the size of the particle-shaped contrast agents injected subcutaneously. Particle size represented passive and active targeting effects, so micron-sized particles produced delayed enhancement.
Conclusion: Choosing the size of iron oxide particles for MR imaging contrast depends on the objective of observation, such as identifying the morphology or migration of immune cells in the lymph node.