Immunotherapy is becoming more frequently used in patients with high grade glioma (HGG) following standard chemoradiation. However, immune-mediated pseudoprogression (PsP) is a growing problem that remains poorly characterized and renders conventional imaging less useful. We evaluate the ability of a novel, advanced diffusion model, restriction spectrum imaging (RSI) to differentiate PsP from TP following immunotherapy. We demonstrate that an RSI-derived measure of axonal integrity (neurite density; ND) can differentiate TP from PsP, correctly classifying 73% of patients. We conclude that lower RSI-ND reflects disruption of axonal microstructure and may provide an imaging marker of tumor infiltration in patients with TP.