MR imaging biomarkers evaluating vascular normalization window after anti-vessel treatment.

The beginning and the end of the vascular normalization window are not clear in response to anti-angiogenic therapies. We used dynamic contrast-enhanced MRI (DCE-MRI) and intravoxel incoherent motion MRI (IVIM-MRI) to noninvasively evaluate the vascular normalization window. MRI was performed five times: before treatment and on the second, fourth, sixth and eighth days of treatment. Quantitative perfusion parameters were calculated at each time point, including the volume transfer coefficient (Ktrans), reverse transfer constant (Kep), pseudodiffusion coefficient (D* ) and perfusion fraction (f). Tumors were evaluated for changes by immunohistochemistry. An increase in Ktrans and Kep was observed after bevacizumab treatment on days 2 and 4. Similar trends were observed for D* and f on days 2 and 4. However, the parameters of Ktrans, Kep, D* and f were decreased on days 6 and 8. A significant increase of the vessel maturity index between the treatment and control groups was measured on days 2 and 4, but this increase abated by days 6 and 8. IVIM and DCE-MRI are helpful when quantifying the tumor perfusion and evaluating the vascular normalization window after anti-vessel therapy. IVIM and DCE-MRI can outline the important period after anti-vessel treatment.