HERBY was a Phase II multicenter trial setup to establish the efficacy and safety of adding bevacizumab to radiation therapy and temozolomide in pediatric patients with newly diagnosed non-brain stem high-grade gliomas. This study evaluates the implementation of the radiologic aspects of HERBY.We analyzed multimodal imaging compliance rates and scan quality for participating sites, adjudication rates and reading times for the central review process, the influence of different Response Assessment in Neuro-Oncology criteria in the final response, the incidence of pseudoprogression, and the benefit of incorporating multimodal imaging into the decision process.Multimodal imaging compliance rates were the following: diffusion, 82%; perfusion, 60%; and spectroscopy, 48%. Neuroradiologists' responses differed for 50% of scans, requiring adjudication, with a total average reading time per patient of approximately 3 hours. Pseudoprogression occurred in 10/116 (9%) cases, 8 in the radiation therapy/temozolomide arm and 2 in the bevacizumab arm (P < .01). Increased target enhancing lesion diameter was a reason for progression in 8/86 cases (9.3%) but never the only radiologic or clinical reason. Event-free survival was predicted earlier in 5/86 (5.8%) patients by multimodal imaging (diffusion, n = 4; perfusion, n = 1).The addition of multimodal imaging to the response criteria modified the assessment in a small number of cases, determining progression earlier than structural imaging alone. Increased target lesion diameter, accounting for a large proportion of reading time, was never the only reason to designate disease progression.