Liver tumor model with implanted rhabdomyosarcoma in rats: MR imaging, microangiography, and histopathologic analysis.

In compliance with institutional regulations for care and use of laboratory animals, the aim of this study was to establish and characterize a rodent liver tumor model to provide a platform for preclinical assessment of new diagnostic and therapeutic strategies. A rhabdomyosarcoma tumor was implanted in the right and left liver lobes of 20 rats, for a total of 40 tumors. T1- and T2-weighted magnetic resonance (MR) images, diffusion-weighted images, and dynamic susceptibility contrast agent-enhanced perfusion-weighted images were obtained up to 16 days after tumor implantation and were compared with postmortem three-dimensional computed tomographic (CT) images, digital microangiograms, and histopathologic findings. Fifteen tumors were examined with proton ((1)H) MR spectroscopy. All tumors grew, with a mean volume doubling time of 2.2 days +/- 0.9 (standard deviation) and a final size of 591 mm(3)+/- 124. The rhabdomyosarcoma tumor showed hypervascularity at MR imaging, three-dimensional CT, microangiography, and histologic analysis. On dynamic susceptibility contrast-enhanced perfusion-weighted images, the maximum signal intensity decrease differed in time and extent between the tumor and the liver, with a significantly (P < .001) higher relative blood volume, relative blood flow, and permeability value in the tumor than in the liver. With (1)H MR spectroscopy, the rhabdomyosarcoma tumor and the liver featured significant (P < .001) choline and lipid peaks, respectively. Implantation of a rhabdomyosarcoma tumor in the livers of rats is feasible and reproducible, and this animal model seems promising for future testing of new diagnostic and therapeutic strategies.

[1]  Y. Ni,et al.  Diffusion-weighted MR imaging in monitoring the effect of a vascular targeting agent on rhabdomyosarcoma in rats. , 2005, Radiology.

[2]  S. Maier,et al.  High-b-value diffusion-weighted MR imaging for pretreatment prediction and early monitoring of tumor response to therapy in mice. , 2004, Radiology.

[3]  Benjamin M Yeh,et al.  Parallel imaging and diffusion tensor imaging for diffusion-weighted MRI of the liver: preliminary experience in healthy volunteers. , 2004, AJR. American journal of roentgenology.

[4]  C. Spenger,et al.  Noninvasive estimation of tumour viability in a xenograft model of human neuroblastoma with proton magnetic resonance spectroscopy (1H MRS) , 2003, British Journal of Cancer.

[5]  Q. Qian,et al.  Relationship between the imaging features and pathologic alteration in hepatoma of rats. , 2003, World journal of gastroenterology.

[6]  C. Zheng,et al.  An implantable rat liver tumor model for experimental transarterial chemoembolization therapy and its imaging features. , 2002, World journal of gastroenterology.

[7]  Catherine Oppenheim,et al.  Which MR-derived perfusion parameters are the best predictors of infarct growth in hyperacute stroke? Comparative study between relative and quantitative measurements. , 2002, Radiology.

[8]  N. Thacker,et al.  Breath‐hold perfusion and permeability mapping of hepatic malignancies using magnetic resonance imaging and a first‐pass leakage profile model , 2002, NMR in biomedicine.

[9]  A. Sorensen,et al.  Comparison of permeability in high-grade and low-grade brain tumors using dynamic susceptibility contrast MR imaging. , 2002, AJR. American journal of roentgenology.

[10]  K. Brindle,et al.  The susceptibility of tumors to the antivascular drug combretastatin A4 phosphate correlates with vascular permeability. , 2001, Cancer research.

[11]  P. Lambin,et al.  In vivo antitumor effect of vascular targeting combined with either ionizing radiation or anti-angiogenesis treatment. , 2001, International journal of radiation oncology, biology, physics.

[12]  G Zaharchuk,et al.  Is All Perfusion-Weighted Magnetic Resonance Imaging for Stroke Equal? The Temporal Evolution of Multiple Hemodynamic Parameters After Focal Ischemia in Rats Correlated With Evidence of Infarction , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[13]  S. Luk,et al.  Evaluation of therapeutic effectiveness of transarterial chemoembolization for hepatocellular carcinoma: correlation of dynamic susceptibility contrast-enhanced echoplanar imaging and hepatic angiography. , 2000, Clinical imaging.

[14]  A. Elster,et al.  Acute cerebral infarction: quantification of spin-density and T2 shine-through phenomena on diffusion-weighted MR images. , 1999, Radiology.

[15]  T. Ichikawa,et al.  Fast magnetic resonance imaging of liver. , 1999, European journal of radiology.

[16]  I. Yamada,et al.  Diffusion coefficients in abdominal organs and hepatic lesions: evaluation with intravoxel incoherent motion echo-planar MR imaging. , 1999, Radiology.

[17]  B. Rosen,et al.  Early changes measured by magnetic resonance imaging in cerebral blood flow, blood volume, and blood-brain barrier permeability following dexamethasone treatment in patients with brain tumors. , 1999, Journal of neurosurgery.

[18]  S. Kawasaki,et al.  Relationship between Doubling Time of Liver Metastases from Colorectal Carcinoma and Residual Primary Cancer , 1998, Digestive Surgery.

[19]  N. Lundbom,et al.  Increased choline signal coinciding with malignant degeneration of cerebral gliomas: a serial proton magnetic resonance spectroscopy imaging study. , 1997, Journal of Neurosurgery.

[20]  A L Baert,et al.  Magnetic resonance imaging, microangiography, and histology in a rat model of primary liver cancer. , 1992, Investigative radiology.

[21]  J. Denekamp.  The choice of experimental models in cancer research: The key to ultimate success or failure? , 1992, NMR in biomedicine.

[22]  Yunfeng Qin,et al.  Quantitative study of the growth of experimental hepatic tumors in rats by using magnetic resonance imaging , 1992, International journal of cancer.

[23]  L. Lumeng,et al.  A reproducible rat liver cancer model for experimental therapy: introducing a technique of intrahepatic tumor implantation. , 1992, The Journal of surgical research.

[24]  B. Balkau,et al.  Liver tumors in cirrhosis: experimental study with SPIO-enhanced MR imaging. , 1991, Radiology.

[25]  R. Weissleder,et al.  Hepatic metastases: rat models for imaging research. , 1989, Magnetic resonance imaging.

[26]  D. Le Bihan,et al.  Separation of diffusion and perfusion in intravoxel incoherent motion MR imaging. , 1988, Radiology.

[27]  M. Poupon,et al.  In vivo emergence of a highly metastatic tumour cell line from a rat rhabdomyosarcoma after treatment with an alkylating agent. , 1988, British Journal of Cancer.

[28]  J. Gore,et al.  Magnetic resonance, pathology and physiology of the BA1112 rhabdomyosarcoma in vivo. , 1988, Investigative radiology.

[29]  J. Wittenberg,et al.  Dynamic spin-echo MRI of liver cancer using Gadolinium-DTPA: animal investigation. , 1986, AJR. American journal of roentgenology.

[30]  G. Barendsen,et al.  Cellular proliferation patterns in an experimental rhabdomyosarcoma in the rat. , 1967, European journal of cancer.