Quantitative MRI assessment of glioma response to bevacizumab in a mouse model

We aimed to investigate the changes of MRI parameters in glioma after bevacizumab treatment and to explore possible pathological mechanism to these changes. Forty-two nude mice with intracranial gliomas were divided two groups: bevacizumab group and control group. Various MRI parameters (tumor volume, apparent diffusion coefficient [ADC], T1w + contrast, dynamic contrast-enhanced-MRI [DCE-MRI]) were acquired before and after treatment. The expression of Ki67, claudin-5, occludin and CD34 were detected and tight junction changes of blood brain barrier were observed. Neovascularization pattern (intussusceptive microvascular growth) in tumor was also observed after treatment. The results showed bevacizumab reduced tumor growth rate and suppressed tumor cell proliferation. Normalized ADC was negatively correlated with the number of Ki67 positive cells in the tumor tissue (R2 = 0.733). Contrast enhancement on T1w + contrast and the Ktrans value acquired from DCE-MRI showed a significant reduction in glioma. Transmission electron microscope showed tight junction was partially regained after bevacizumab treatment. Meanwhile, claudin-5 and occludin expression increased. In bevacizumab group, the number of intussusceptive microvascular growth (3.83 ± 1.17) in tumor was higher than that in control group (1.16 ± 0.75) (P < 0.05). Ktrans value was negatively correlated with intussusceptive microvascular growth (R 2 = 0.7396) and normalized contrast enhancement value was negatively correlated with claudin-5 and occludin expression (R2 = 0.831, 0.924) in tumor. In conclusion, bevacizumab effectively reduced the Ktrans and T1w + contrast values. The mechanisms might involve neovascularization pattern change and reformation of tight junction. And ADC, Ktrans and T1w + contrast might be noninvasive biomarkers to predict cell proliferation, neovascularization pattern and tight junction change in a U87 glioma model. These findings might provide some new guidance to glioma therapy.