Using semi-quantitative dynamic contrast-enhanced magnetic resonance imaging parameters to evaluate tumor hypoxia: A preclinical feasibility study in a maxillofacial VX2 rabbit model

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.