Evaluation of antiangiogenic and antiproliferative effects of sorafenib by sequential histology and intravoxel incoherent motion diffusion‐weighted imaging in an orthotopic hepatocellular carcinoma xenograft model

Purpose To investigate the effectiveness of intravoxel incoherent motion (IVIM) in the assessment of the therapeutic efficacy of sorafenib in an orthotopic hepatocellular carcinoma (HCC) xenograft model. Materials and Methods Thirty‐five HCC nude mouse models were established. IVIM was performed on...

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Published in:Journal of magnetic resonance imaging 2017-01, Vol.45 (1), p.270-280
Main Authors: Yang, Shuo‐hui, Lin, Jiang, Lu, Fang, Han, Zhi‐hong, Fu, Cai‐xia, Lv, Peng, Liu, Hao, Gao, Dong‐mei
Format: Article
Language:English
Subjects:
Angiogenesis Inhibitors - administration & dosage
Animals
Antineoplastic Agents - administration & dosage
Carcinoma, Hepatocellular - diagnostic imaging
Carcinoma, Hepatocellular - drug therapy
Carcinoma, Hepatocellular - pathology
Cell Line, Tumor
Cell Proliferation - drug effects
Diffusion
Diffusion Magnetic Resonance Imaging - methods
hepatocellular carcinoma
Histology
Image Enhancement - methods
Image Interpretation, Computer-Assisted - methods
intravoxel incoherent motion
Liver cancer
Liver Neoplasms - diagnostic imaging
Liver Neoplasms - drug therapy
Liver Neoplasms - pathology
Magnetic Resonance Angiography - methods
Magnetic resonance imaging
Male
Mice
Mice, Inbred BALB C
micro‐vessel density
Motion
necrosis
Neovascularization, Pathologic - diagnostic imaging
Neovascularization, Pathologic - drug therapy
Neovascularization, Pathologic - pathology
Niacinamide - administration & dosage
Niacinamide - analogs & derivatives
Phenylurea Compounds - administration & dosage
Reproducibility of Results
Rodents
Sensitivity and Specificity
sorafenib
Treatment Outcome
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Summary:Purpose To investigate the effectiveness of intravoxel incoherent motion (IVIM) in the assessment of the therapeutic efficacy of sorafenib in an orthotopic hepatocellular carcinoma (HCC) xenograft model. Materials and Methods Thirty‐five HCC nude mouse models were established. IVIM was performed on a 1.5T MR scanner at baseline (n = 5) and serially at 7, 14, and 21 days after sorafenib treatment. The apparent diffusion coefficient (ADCtotal), true diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) at these timepoints were measured and compared between the treated (n = 15) and control group (n = 15). Differences in measurements among different timepoints were evaluated. Correlations between IVIM parameters and histologic features including necrotic fraction (NF) and microvessel density (MVD) were analyzed. Results Compared to the control group, ADCtotal and D were significantly higher at each timepoint (P = 0.009), while f significantly decreased at 7 days (P = 0.009) and increased at 21 days (P = 0.028) in the treated group. Serial measurements in the treated group showed that both ADCtotal and D increased significantly at 7, 14, and 21 days compared to baseline (P < 0.05), while f significantly declined at 7 days (P = 0.016) and increased at 21 days (P = 0.009). Significant correlations were found between ADCtotal and NF (r = 0.811, P < 0.001), D and NF (r = 0.838, P < 0.001), and between f and NF (r = 0.528, P = 0.017) in the treated group. Conclusion IVIM may provide useful biomarkers for evaluating the therapeutic effects of sorafenib on HCC. Level of Evidence: 1 J. Magn. Reson. Imaging 2017;45:270–280.
ISSN:1053-1807
1522-2586
DOI:10.1002/jmri.25344