MRI of iron-oxide labelled transplanted hepatocytes in mice : effect of treatment with cyclophosphamide

PURPOSE:: To assess if 1.5T MRI can be used to study the transport to the liver, the intrahepatic distribution and engraftment of iron-oxide labelled hepatocytes in cyclophosphamide-treated and untreated mice. MATERIALS AND METHODS:: Hepatocytes were isolated from C57bl/6 mice and were labelled with 1.63 mum iron-oxide particles. Seventeen mice were pretreated with cyclophosphamide to disrupt the sinusoidal endothelium and 15 were left untreated. Seven days after splenic injection of the labelled hepatocytes, T2*-weighted gradient-echo images at 1.5T were acquired. The hepatic transport, distribution and engraftment of the labelled hepatocytes were assessed with signal intensity (SI) and T2* measurements, electron paramagnetic resonance (EPR), texture analysis and histology. RESULTS:: Lower hepatic SI (P = 0.005), lower T2* (P = 0.033) and larger number of particles at histology (P = 0.006) suggested increased transport to the liver of labelled hepatocytes in cyclophosphamide-treated mice versus untreated mice. At histology, most particles were located in Kupffer cells. Particles distribution was heterogeneous. No difference between both groups was observed at texture analysis. CONCLUSION:: MRI is useful to assess the transport to the liver and intrahepatic distribution of transplanted labelled hepatocytes. The preferential location of iron-oxide particles within Kupffer cells after seven days limits the value of MRI for assessing hepatocyte engraftment. J. Magn. Reson. Imaging 2010;32:367-375. (c) 2010 Wiley-Liss, Inc.