Evaluation of cellular water exchange in a mouse glioma model using dynamic contrast-enhanced MRI with two flip...

This manuscript aims to evaluate the robustness and significance of the water efflux rate constant (k_io) parameter estimated using the two flip-angle Dynamic Contrast-Enhanced (DCE) MRI approach with a murine glioblastoma model at 7 T. The repeatability of contrast kinetic parameters and k_io measurement was assessed by a test-retest experiment (n = 7). The association of k_io with cellular metabolism was investigated through DCE-MRI and FDG-PET experiments (n = 7). Tumor response to a combination therapy of bevacizumab and fluorouracil (5FU) monitored by contrast kinetic parameters and k_io (n = 10). Test-retest experiments demonstrated compartmental volume fractions (v_e and v_p) remained consistent between scans while the vascular functional measures (F_p and PS) and k_io showed noticeable changes, most likely due to physiological changes of the tumor. The standardized uptake value (SUV) of tumors has a linear correlation with k_io (R² = 0.547), a positive correlation with F_p (R² = 0.504), and weak correlations with v_e (R² = 0.150), v_p (R² = 0.077), PS (R² = 0.117), K^trans (R² = 0.088) and whole tumor volume (R² = 0.174). In the treatment study, the k_io of the treated group was significantly lower than the control group one day after bevacizumab treatment and decreased significantly after 5FU treatment compared to the baseline. This study results support the feasibility of measuring k_io using the two flip-angle DCE-MRI approach in cancer imaging.