PURPOSE:To test the feasibility of semi-quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters for evaluating tumor hypoxia in a maxillofacial VX2 rabbit model. METHODS:Eight New Zealand rabbits were inoculated with VX2 cell solution to establish a maxillofacial VX2 rabbit model. DCE-MRI were carried out using a 1.5 Tesla scanner. Semi-quantitative DCE-MRI parameters, maximal enhancement ratio (MER) and slope of enhancement (SLE), were calculated and analyzed. The tumor samples from rabbits underwent hematoxylin-eosin (HE), pimonidazole (PIMO) and vascular endothelial growth factor (VEGF) immunohistochemistry (IHC) staining, and the PIMO area fraction and VEGF IHC score were calculated. Spearman's rank correlation analysis was used for statistical analysis. RESULTS:The MER values of eight VX2 tumors ranged from 1.132 to 1.773 (1.406 ± 0.258) and these values were negatively correlated with the corresponding PIMO area fraction (p = 0.0000002), but there was no significant correlation with the matched VEGF IHC score (p = 0.578). The SLE values of the eight VX2 tumors ranged from 0.0198 to 0.0532 s(-1) (0.030 ± 0.011 s(-1)). Correlation analysis showed that there was a positive correlation between SLE and the corresponding VEGF IHC score (p = 0.0149). However, no correlation was found between SLE and the matched PIMO area fraction (p = 0.662). The VEGF positive staining distribution predominantly overlapped with the PIMO adducts area, except for the area adjacent to the tumor blood vessel. CONCLUSIONS:The semi-quantitative parameters of DCE-MRI, MER and SLE allowed for reliable measurements of the tumor hypoxia, and could be used to noninvasively evaluate hypoxia during tumor treatment.

The purpose of this study was to investigate the correlations between Gd-EOB-DTPA DCE-MRI biomarkers and histopathologic biomarkers of liver fibrosis progression in a rabbit model of liver fibrosis. Thirty-Six New Zealand white rabbits were randomly divided into control (n = 6) and liver fibrosis group (n = 30). Each rabbit in the liver fibrosis group received a weekly subcutaneous injection in the back comprising 50% carbon tetrachloride (CCl₄) in oily solution. Control rabbits received subcutaneous injections with the same amount of normal saline solution instead. MR imaging was performed in control and fibrotic rabbits were conducted by MRI at week 0 (n = 36). The fibrotic rabbits were performed MR imaging on 6 weeks, 9 weeks, and 12 weeks after modeling of fibrosis. Before each MRI, peripheral blood was collected, and several biochemical testes are performed. The thirty-four rabbits completed this study. They were then divided into three subgroups according to fibrotic stage: no fibrosis (F0, n = 12), mild fibrosis (F1+F2, n = 14), and advanced fibrosis (F3+F4, n = 8). DCE-MRI measurements show increasing K^trans and V_e while decreasing iACU90 with increasing fibrosis stage. The significant correlations were observed between mean K^trans, V_e, iACU90 and percentage of the animal with mild liver fibrosis. For blood biomarkers, there were significant differences between F0 and F1+F2, and between F0 and F3+F4 in the serum levels of ALT (all P < 0.05), and TB (F0 vs. F1+F2, P = 0.004), while no differences were found between F1+F2 group and F3+F4 group (all P > 0.05). There were significant differences between F0 and F1+F2 (P = 0.02). Gd-EOB-DTPA DCE-MRI is a promising method for the noninvasive diagnosis and staging of liver fibrosis. Future studies to evaluate the effectiveness of these techniques in patients with liver fibrosis are warranted.