Abstract
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) (R(2) = 0.547), a positive correlation with F(p) (R(2) = 0.504), and weak correlations with v(e) (R(2) = 0.150), v(p) (R(2) = 0.077), PS (R(2) = 0.117), K(trans) (R(2) = 0.088) and whole tumor volume (R(2) = 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.