OBJECTIVE : Baseline diffusion or apparent diffusion coefficient (ADC) characteristics have been shown to predict outcome related to DIPG, but the predictive value of post-radiation ADC is less well understood. ADC parametric mapping (FDM) was used to measure radiation-related changes in ADC and compared these metrics to baseline ADC in predicting progression-free survival and overall survival using a large multi-center cohort of DIPG patients (Pediatric Brain Tumor Consortium-PBTC). METHODS : MR studies at baseline and post-RT in 95 DIPG patients were obtained and serial quantitative ADC parametric maps were generated from diffusion-weighted imaging based on T2/FLAIR and enhancement regions of interest (ROIs). Metrics assessed included total voxels with: increase in ADC (iADC); decrease in ADC (dADC), no change in ADC (nADC), fraction of voxels with increased ADC (fiADC), fraction of voxels with decreased ADC (fdADC), and the ratio of fiADC and fdADC (fDM Ratio). RESULTS : A total of 72 patients were included in the final analysis. Tumors with higher fiADC between baseline and the first RT time point showed a trend toward shorter PFS with a hazard ratio of 6.44 (CI 0.79, 52.79, p = 0.083). In contrast, tumors with higher log mean ADC at baseline had longer PFS, with a hazard ratio of 0.27 (CI 0.09, 0.82, p = 0.022). There was no significant association between fDM derived metrics and overall survival. CONCLUSIONS : Baseline ADC values are a stronger predictor of outcome compared to radiation related ADC changes in pediatric DIPG. We show the feasibility of employing parametric mapping techniques in multi-center studies to quantitate spatially heterogeneous treatment response in pediatric tumors, including DIPG.