Morphological and carbogen‐based functional MRI of a chemically induced liver tumor model in mice

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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‐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. Magn Reson Med 50:522–530, 2003.