Application of magnetic resonance imaging in transgenic and chemical mouse models of hepatocellular carcinoma.
BACKGROUND
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The molecular mechanisms underlying hepatocarcinogenesis are still poorly understood. Genetically modified mice are powerful tools to further investigate the mechanisms of HCC development. However, this approach is limited due to the lack of non-invasive detection methods in small rodents. The aim of this study was to establish a protocol for the non-invasive analysis of hepatocarcinogenesis in transgenic mice using a clinical 1.5 Tesla Magnetic Resonance Imaging scanner.


RESULTS
As a model system we used hepatocyte-specific c-myc transgenic mice developing hepatocellular carcinoma at the age of 12-15 months. The scans of the murine livers included axial T2-weighted turbo-spin echo (TSE) images, axial T1-weighted and contrast enhanced T1-weighted gradient echo (fast field echo, FFE) and sagittal true Fast Imaging with Steady state Precession (true-FISP) images. Application of contrast agent was performed via tail vein-catheter and confirmed by evaluation of the altered longitudinal relaxation T1 time before and after application. Through technical adaptation and optimization we could detect murine liver lesions with a minimum diameter of approximately 2 mm and provided histopathological evidence that these MR findings correspond to hepatocellular carcinoma. Tumor growth was repeatedly measured using sequential MRI with intervals of 5 weeks and subsequent volumetric analysis facilitating direct comparison of tumor progression between individual animals. We finally demonstrated that our protocol is also applicable in the widely- used chemical model of N-nitrosodiethylamine-induced hepatocarcinogenesis.


CONCLUSIONS
Our protocol allows the non-invasive, early detection of HCC and the subsequent continuous monitoring of liver tumorgenesis in transgenic mice thereby facilitating future investigations of transgenic tumor mouse models of the liver.
Freimuth
Julia
J
UCSF Helen Diller Family Comprehensive Cancer Center 1450, 3rd Street, San Francisco, CA 94158-9001, USA.
Gassler
Nikolaus
N
Moro
Nives
N
Günther
Rolf W
RW
Trautwein
Christian
C
Liedtke
Christian
C
Krombach
Gabriele A
GA
D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000175:diagnosis* / Q000235:genetics; D004052:Diethylnitrosamine / Q000633:toxicity; D004195:Disease Models, Animal; D016259:Genes, myc; D007150:Immunohistochemistry; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000175:diagnosis* / Q000235:genetics; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic
D000477:Alkylating Agents; D004052:Diethylnitrosamine