Significance The inability to accurately monitor glioblastoma tumor progression vs. pseudoprogression has severely limited clinical treatment decisions, especially in the setting of immunotherapy. We have identified a novel noninvasive imaging combination that could distinguish intracranial immune responses from tumor progression in mice bearing orthotopic gliomas and in patients with glioblastomas. We combined the use of advanced MRI with PET imaging of deoxycytidine kinase, an enzyme overexpressed in immune cells. This combination resulted in superior differentiation between immune responses and tumors within the brain, and identified peripheral lymph nodes in which immune responses occurred after immunotherapy combinations. This combined imaging approach may provide a useful method to clinically monitor patients with glioblastomas treated with immune-based therapies, and to distinguish tumor progression from pseudoprogression.