Evaluation of Tumor Hypoxia in C6 Glioma Rat Model With Dynamic Contrast-Enhanced Magnetic Resonance Imaging

Abstract

To investigate the feasibility of determining quantitative parameters for evaluating tumor hypoxia in the C6 glioma model by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Thirty male Sprague-Dawley rats were inoculated to establish C6 brain glioma models. DCE-MRI scans were performed 14, 21, and 28 days after transplantation. Quantitative parameters comprising Ktrans, Ve, Kep, and Vp were calculated and analyzed. At the end of each scan, 10 rats were randomly selected for immunohistochemical (IHC) staining of hypoxia-inducible factor-17αl (HIF-1α), proliferating cell nuclear antigen (PCNA), and CD34. Correlations between quantitative parameters and IHC scores were analyzed. The tumor volumes increased with time. The Ktrans values on days 14, 21, and 28 were 0.03 ± 0.009 min-1, 0.084 ± 0.010 min-1, and 0.050 ± 0.016 min-1, while the Ve values were 0.17 ± 0.070, 0.46 ± 0.159, and 0.51 ± 0.193, the Kep values were 0.18 ± 0.070%, 0.220 ± 0.049%, and 0.06 ± 0.035%, and these three parameters all differed significantly among the three time points. The Vp values on days 14, 21, and 28 were 0.09 ± 0.040%, 0.120 ± 0.034%, and 0.06 ± 0.010%, but the values did not differ among the three time points (P = 0.073). Ktrans had significant negative correlations with the HIF-1α scores on days 14 and 21 when there was also a positive correlation between Ktrans and CD34. Ve had negative correlations with the HIF-1α score on days 14 and 21, and there was a negative correlation between Ve and PCNA on day 21. Kep had a negative correlation with the HIF-1α score and a positive correlation with MVD on day 21. DCE-MRI may be a useful method for the noninvasive evaluation of the hypoxia status in a glioma model.