Evaluation of HIF-1α Expression in a Rat Glioma Model Using Intravoxel Incoherent Motion and R2*Mapping

Accurate evaluation of HIF-1 alpha levels can facilitate the detection of hypoxia niches in glioma and treatment decisions. To investigate the feasibility of intravoxel incoherent motion (IVIM) and R2* Mapping for detecting HIF-1 alpha expression levels, sixteen rats with intracranial C6 gliomas were subjected to IVIM and R2* Mapping using a 7 Tesla MRI scanner. For each model, the brain tissue on the HIF-1 alpha-stained slices was subdivided into multiple square regions of interest (ROIs) with areas of 1 mm(2), for which HIF-1 alpha expression was assessed by HALO software to form a maps of HIF scores with a 0-300 range. The IVIM and R2* Mapping images were processed to create maps of the D, D*, f and R2* that were then paired with the corresponding HIF score maps. The average D, D*, f, perfusion (f x D*) and R2* values were calculated for the ROIs in the tumor and normal brain regions with different HIF-1 alpha levels and used in further analysis. In this study, the average tumor size of sixteen C6 model rats was 458 +/- 46.52 mm(3), and the 482 included ROIs consisted of 280 tumoral and 202 normal ROIs. The average HIF score for the tumor regions was significantly higher than normal brain tissue (p < 0.001), and higher HIF scores were obtained for the central part of tumors than peripheral parts (p=0.03). Compared with normal brain tissues, elevated perfusion and f values were observed in tumor regions (p = 0.021, 0.004). In tumoral ROIs, the R2* values were higher in the group with high HIF-1 alpha expression than in the group with low HIF-1 alpha expression (p = 0.003). A correlation analysis revealed a positive correlation between the R2* value and HIF scores (r = 0.43, p < 0.001) and a negative correlation between D* and the HIF scores (r = -0.30, p = 0.001). Discrepancies in HIF-1 alpha expression were found among different intratumoral areas, and IVIM and R2* Mapping were found to be promising means of noninvasive detection of the distribution and expression level of HIF-1 alpha.