Liver positive enhancement after injection of superparamagnetic nanoparticles: respective role of circulating and uptaken particles.

Superparamagnetic nanoparticles have both high r1 and r2 relaxivities responsible for positive or negative enhancement properties. The aim of this study was to investigate to what extent perfusion (circulating particles) and uptake (clustered particles) mechanisms contribute to liver positive or negative enhancement using two different particles, superparamagnetic iron oxides (ferumoxides, AMI 25) and ultrasmall superparamagnetic iron oxides (ferumoxtran, AMI-227). Uptake kinetics were studied after intravenous injection of 20 micromol Fe/kg ferumoxtran on a washout liver model. Livers of 82 rats were surgically isolated and washed with saline infusion. Imaging was performed ex vivo at 0.5T with T1- and T2-weighted sequences. Enhancement kinetics of the liver were studied in vivo using MRI up to 180 min post injection of 20 micromol Fe/kg ferumoxtran (time response study) or 10, 20, 40 micromol Fe/kg ferumoxtran and 20 micromol Fe/kg ferumoxides (dose response study.) Particle uptake occurred early and resulted in a negative enhancement of the washed livers 15 min after injection of both T1 and T2 sequences. In vivo, a positive enhancement was only seen during the first five min with the lowest dose of ultrasmall superparamagnetic iron oxides and the T1 sequence. Uptake and clustering of the particles induced a negative liver enhancement. During the first minutes after injection, when uptake has not significantly occurred, perfusion imaging of the liver at a dose of 10 micromol Fe/kg results in a positive enhancement with T1-weighted sequences.