title: Morphological and carbogen-based functional MRI of a chemically induced liver tumor model in mice.
abstract: A multifocal mouse liver tumor model chemically induced with 5,9-dimethyl-7H-dibenzo[c,g]carbazole was investigated by respiratory-triggered morphological and functional MRI (fMRI) at 4.7 Tesla. The model is characterized by the presence of two tumor types: hypovascular cholangioma and vascularized hepatocellular carcinoma (HCC). Growth curves measured by 3D-MRI showed limited growth of cholangiomas and rapid growth of HCCs after a latency of about 25 weeks. Functional imaging based on T(2) (*)-weighted fast gradient-echo MRI and carbogen breathing was optimized for liver imaging in mice. A response to carbogen was observed in HCCs but not in cholangiomas. Transversal analysis (50 HCCs) of signal change upon carbogen revealed four different types of response patterns: 1) signal increase upon carbogen administration (74%); 2) small or insignificant signal change (10%), 3) transient signal decrease and delayed increase (8%), and 4) signal decrease (8%). Longitudinal follow-up of a subgroup (N = 17) showed that an initially observed type 1 response, attesting to the presence of a functional vasculature, remained stable for at least 3 weeks in 14 HCCs. A switch from a type 1 response to another response type may be useful for demonstrating, in a noninvasive manner, a disturbance of tumor vasculature induced by anti-vascular or anti-angiogenic therapy.
authors.affiliation: INSERM U350, Curie Institute-Research Division, Centre Universitaire, Orsay, France. carole.thomas@curie.u-psud.fr
authors.forename: Carole D
authors.initials: CD
authors.lastname: Thomas
authors.forename: Evelyne
authors.initials: E
authors.lastname: Chenu
authors.forename: Christine
authors.initials: C
authors.lastname: Walczak
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Plessis
authors.forename: François
authors.initials: F
authors.lastname: Perin
authors.forename: Andreas
authors.initials: A
authors.lastname: Volk
mesh_terms: D000818:Animals; D002227:Carbazoles; D002245:Carbon Dioxide / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000473:pathology*; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D010100:Oxygen / Q000008:administration & dosage*; D010865:Pilot Projects; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*
chemical_list: D002227:Carbazoles; D011838:Radiation-Sensitizing Agents; C041514:carbazole; D002245:Carbon Dioxide; C011700:carbogen; D010100:Oxygen