Radiotherapy is part of the standard treatment of most primary brain tumors. Large clinical target volumes and physical characteristics of photon beams inevitably lead to irradiation of surrounding normal brain tissue. This can cause radiation-induced brain injury. In particular, late brain injury, such as cognitive dysfunction, is often irreversible and progressive over time, resulting in a significant reduction in quality of life. Since 50% of patients have survival times greater than six months, radiation-induced side effects become more relevant and need to be balanced against radiation treatment given with curative intent. To develop adequate treatment and prevention strategies, the underlying cause of radiation-induced side-effects needs to be understood. This paper provides an overview of radiation-induced changes observed in normal-appearing brains measured with conventional and advanced MRI techniques and summarizes the current findings and conclusions. Brain atrophy was observed with anatomical MRI. Changes in tissue microstructure were seen on diffusion imaging. Vascular changes were examined with perfusion-weighted imaging and susceptibility-weighted imaging. MR spectroscopy revealed decreasing N-acetyl aspartate, indicating decreased neuronal health or neuronal loss. Based on these findings, multicenter prospective studies incorporating advanced MR techniques as well as neurocognitive function tests should be designed in order to gain more evidence on radiation-induced sequelae.

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Imaging biomarkers capable of distinguishing between tumor recurrence and treatment effect are of high relevance for radiation therapy. In 14 glioma patients, we analyzed changes in relative cerebral blood volume (rCBV) in areas of hyperintensities on T2-weighted magnetic resonance imaging (MRI) appearing after irradiation with protons. rCBV values were evaluated comparing the baseline and the latest follow-up measurement both visually and based on histograms. A significant rCBV perfusion decrease was observed in those hyperintensities, which may be interpreted as treatment effect. Further work is needed correlating the rCBV changes with histology and patient outcome.