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.
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.



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.



Compared to the control group, ADCtotaland 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 ADCtotaland 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 ADCtotaland 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.



IVIM may provide useful biomarkers for evaluating the therapeutic effects of sorafenib on HCC.



1 J. Magn. Reson. Imaging 2017;45:270-280.
Department of Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, and Shanghai Institute of Medical Imaging, Shanghai, China.
Shuo-Hui
SH
Yang
Department of Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, and Shanghai Institute of Medical Imaging, Shanghai, China.
Jiang
J
Lin
Department of Radiology, Shuguang Hosipital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Fang
F
Lu
Department of Pathology, Shuguang Hosipital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Zhi-Hong
ZH
Han
Siemens Shenzhen Magnetic Resonance Ltd., Shenzhen, China.
Cai-Xia
CX
Fu
Department of Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, and Shanghai Institute of Medical Imaging, Shanghai, China.
Peng
P
Lv
Department of Radiology, Zhongshan Hospital, Shanghai Medical College, Fudan University, and Shanghai Institute of Medical Imaging, Shanghai, China.
Hao
H
Liu
Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
Dong-Mei
DM
Gao
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009038:Motion; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000473:pathology; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000077157:Sorafenib; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib
hepatocellular carcinoma; intravoxel incoherent motion; micro-vessel density; necrosis; sorafenib