Intravenous MR lymphography with superparamagnetic iron oxide particles: experimental studies in rats and rabbits

The inter- and intralymphonodal distribution of IV-administered superparamagnetic iron oxide (SPIO) particles as a lymphographic contrast agent for MRI was studied in various animal models in rats and rabbits. In all animals a dosage of 200 mol Fe/kg was tested. Imaging was done at 1.5 Tesla using proton-density-weighted spin-echo (PD-SE) and T2^*-weighted gradient-echo (T2^*-GRE) sequences. The time course of signal loss in popliteal lymph nodes of 21 rats was studied before and up to 72 h after IV injection of SPIO. Another 6 rats were dissected 24 h after IV injection of SPIO, all lymph nodes were embedded in agar gel and imaged ex vivo. Time course and pattern of lymph node signal loss was studied in 6 rabbits with reactive lymph node hyperplasia. The visualization of lymph node metastases was studied in 4 VX2 tumor-bearing rabbits. Most pronounced signal loss in lymph nodes was found 24 h after IV injection of SPIO with a decrease of signal in popliteal lymph nodes to 37 ± 15% (9 ± 5%) for rats and 56 ± 10% (16 ± 9%) for rabbits with the PD-SE (T2^*-GRE) sequence. Ex vivo examinations of rat lymph nodes and in vivo examinations in rabbits with lymph node hyperplasia demonstrated marked variations in contrast agent accumulation between different lymph node groups. In VX2 tumor-bearing rabbits lymph node metastases could be well delineated in postcontrast MRI if a sufficient amount of contrast agent reached the lymph nodes (2 rabbits). Inhomogeneous signal loss as well as supersaturation impeded correct lymph node assessment (2 rabbits). We conclude that IV MR lymphography using SPIO may be an approach for non invasive tumor staging, but this new technique could be limited by variations in contrast agent distribution between different lymph node groups.