Graded functional diffusion map-defined characteristics of apparent diffusion coefficients predict overall survival in recurrent glioblastoma treated with bevacizumab

Diffusion imaging has shown promise as a predictive and prognostic biomarker in glioma. We assessed the ability of graded functional diffusion maps (fDMs) and apparent diffusion coefficient (ADC) characteristics to predict overall survival (OS) in recurrent glioblastoma multiforme (GBM) patients treated with bevacizumab. Seventy-seven patients with recurrent GBMs were retrospectively examined. MRI scans were obtained before and approximately 6 weeks after treatment with bevacizumab. Graded fDMs were created by registering data-sets to each patient's pretreatment scan and then performing voxel-wise subtraction between post- and pretreatment ADC maps. Voxels were categorized according to the degree of change in ADC within pretreatment fluid-attenuated inversion recovery (FLAIR) and contrast-enhancing regions of interest (ROIs). We found that the volume of tissue showing decreased ADC within both FLAIR and contrast-enhancing regions stratified OS (log-rank, P < .05). fDMs applied to contrast-enhancing ROIs more accurately predicted OS compared with fDMs applied to FLAIR ROIs. Graded fDMs (showing voxels with decreased ADC between 0.25 and 0.4 mu m(2)/ms) were more predictive of OS than traditional (single threshold) fDMs, and the predictive ability of graded fDMs could be enhanced even further by adding the ADC characteristics from the fDM-classified voxels to the analysis (log-rank, P < .001). These results demonstrate that spatially resolved diffusion-based tumor metrics are a powerful imaging biomarker of survival in patients with recurrent GBM treated with bevacizumab.