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In vivo imaging of transplanted hepatocytes with a 1.5-T clinical MRI system—initial experience in mice

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Abstract

The feasibility of in vitro mature mouse hepatocyte labeling with a novel iron oxide particle was assessed and the ability of 1.5-T magnetic resonance imaging (MRI) to track labeled mouse hepatocytes in syngenic recipient livers following intraportal cell transplantation was tested. Mouse hepatocytes were incubated with anionic iron oxide nanoparticles at various iron concentrations. Cell viability was assessed and iron oxide particle uptake quantified. Labeled hepatocytes were intraportally injected into 20 mice, while unlabeled hepatocytes were injected into two mice. Liver T2 values, spleen-to-muscle relative signal intensity (RI spleen/muscle ), and liver-to-muscle relative signal intensity (RI liver/muscle ) on gradient-echo T2-weighted imaging after injection of either labeled or unlabeled hepatocytes were compared with an ANOVA test followed by Fisher’s a posteriori PLSD test. Livers, spleens and lungs were collected for histological analysis. Iron oxide particle uptake was saturable with a maximum iron content of 20 pg per cell and without viability alteration after 3 days of culture. Following labeled-cell transplantation, recipient livers showed well-defined nodular foci of low signal intensity on MRI—consistent with clusters of labeled hepatocytes on pathological analysis—combined with a significant decrease in both liver T2 values and liver-to-muscle RI liver/muscle (P = 0.01) with minimal T2 values demonstrated 8 days after transplantation. Conventional MRI can demonstrate the presence of transplanted iron-labeled mature hepatocytes in mouse liver.

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Acknowledgements

This work was supported in part by the following grants: Canceropole Ile de France—INCa—2004; ACI Neurosciences 03-5-295; GIS Maladies Rares A 03 087 DS.The authors wish to thank the MR team of the Imaging Department at CHU Henri Mondor, Faculte de Medecine Paris XII, Creteil, France, and especially Dr Pierre Brugières (MD) and Pierre Zerbib for their contribution in MR experiments. We also thank Dr Catherine Vayssettes for her help in animal experiments.

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Authors and Affiliations

  1. Assistance Publique Hôpitaux de Paris, Radiology Department, CHU Henri Mondor, Créteil, France

    Alain Luciani & Alain Rahmouni

  2. Laboratoire de Recherche en Imagerie, EA 4062, Université Paris Descartes, Hopital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, 20 Rue Leblanc, 75015, Paris, France

    Alain Luciani, Pierre Smirnov & Olivier Clement

  3. INSERM EMI 00 20, and University Paris XI, CHU Bicètre, Kremlin Bicêtre, France

    Alexandre Parouchev, Gustavo Braga, Lyes Boudechiche, Aurore L’Hermine-Coulomb, Ibrahim Dagher, Dominique Franco, Michèle Hadchouel & Anne Weber

  4. CNRS UMR 7057, Matières et systêmes complexes, Université Paris VII, Paris, France

    Pierre Smirnov, Claire Wilhelm & Florence Gazeau

  5. CHLI Antoine Beclers, Chirurgie Viscerale, Clamart, France

    Ibrahim Dagher & Dominique Franco

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  1. Alain Luciani
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Correspondence to Olivier Clement.

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Luciani, A., Parouchev, A., Smirnov, P. et al. In vivo imaging of transplanted hepatocytes with a 1.5-T clinical MRI system—initial experience in mice. Eur Radiol 18, 59–69 (2008). https://doi.org/10.1007/s00330-007-0750-7

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  • DOI: https://doi.org/10.1007/s00330-007-0750-7

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