Krauze AV, Rowe L, Camphausen K and Smart D
The ability to define and ultimately manage normal tissue injury in the brain remains limited as neither pathologic nor radiographic features have a clear correlation with clinical presentation. Normal tissue injury in the brain is often defined clinically by the development of late neurocognitive dysfunction affecting memory, executive function, learning ability and attention, not attributed to tumor progression or other comorbidities. Meanwhile the clinical manifestations of normal tissue injury affect a significant proportion of glioma patients at some point in the course of their treatment and are especially relevant with increasing life expectancy observed in both adult and pediatric patients. In addition, normal tissue toxicity and its clinical implications have become an increasingly important outcome measures in patients with glioma that merit both a better definition (clinical, radiographic, molecular) and better management options as they transition to a potential biomarkers for outcome. The use of imaging as a tool to investigate normal tissue injury represents a noninvasive modality that in conjunction with thorough neurocognitive and quality of life testing can help define and guide management of normal tissue injury related treatment sequelae in patients with glioma. This review discusses the imaging modalities currently employed to investigate normal tissue toxicity incurred by patients with glioma as a result of both tumor and treatment associated injury and future directions for research and treatment.