Cell invasion,motility, and proliferation level estimate (CIMPLE) maps derived from serial diffusion MR images in recurrent glioblastoma treated with bevacizumab

Microscopic invasion of tumor cells and undetected tumor proliferation is the primary reason for a dismal prognosis in glioblastoma patients. Identification and quantification of spatially localized brain regions undergoing high rates of cell migration and proliferation is critical for improving patient survival; however, there are currently no non-invasive imaging biomarkers for estimating proliferation and migration rates of human gliomas in vivo. To accomplish this, we developed CIMPLE (cell invasion, motility, and proliferation level estimates) image maps using serial diffusion MRI scans and a solution to a glioma growth model equation. CIMPLE represent a novel method of quantifying the level of aggressive malignant behavior. In the current pilot study, we demonstrate the utility of CIMPLE maps to predict progression free survival (PFS) and overall survival (OS) in 26 recurrent glioblastoma patients treated with bevacizumab from our Neuro-Oncology database. Voxel-wise estimates of cell proliferation rate predicted spatial regions of contrast enhancement in 35% of patients. A linear correlation was found between the mean proliferation rate and progression-free survival (PFS; P < 0.0001) as well as overall survival (OS; P = 0.0093). Similarly, the mean proliferation rate was able to stratify patients with early and late PFS as well as OS.