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


METHODS
Hepatocytes were isolated from C57bl/6 mice and were labelled with 1.63 microm 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.


CONCLUSIONS
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.
Leconte
Isabelle
I
Radiodiagnostic Unit, Université Catholique de Louvain, St-Luc University Hospital, Brussels, Belgium. isabelle.leconte@uclouvain.be
Pallu
Stéphane
S
Abarca-Quinones
Jorge
J
Michoux
Nicolas
N
Peeters
Frank
F
Radermacher
Kim
K
Sempoux
Christine
C
Najimi
Mustapha
M
Sokal
Etienne
E
Van Beers
Bernard E
BE
D000818:Animals; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods*; D003520:Cyclophosphamide / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods; D005290:Ferric Compounds / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008099:Liver / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission / Q000379:methods; D013154:Spleen / Q000473:pathology
D005290:Ferric Compounds; D007166:Immunosuppressive Agents; C000499:ferric oxide; D003520:Cyclophosphamide