Investigation of magnetic resonance imaging biomarkers of radiation effects on healthy mice brain tissue and Glioblastoma treatment

Abstract

In the field of clinical oncology, radiotherapy is one of the most extensively applied anticancer treatments. However, the ionizing radiation (IR) is absorbed not only by the targeted cells, but also by the surrounding normal cells as well. Consequently, patients may experience symptoms associated with a damage to normal tissues a few weeks, months or years after a course of radiotherapy. We applied a right brain hemisphere radiation technique for mice that mimics radiation exposure during radiotherapy. We investigated several possible brain imaging biomarkers for radiation-induced damage, such as demyelination, axonal injury and inflammation, at different time points post-irradiation (IR). Because Glioblastoma Multiform (GBM) can provoke a more infiltrative phenotype in GBM cells which survive treatment, scans of the brain were obtained using different Magnetic Resonance Imaging (MRI) modalities, including Diffusion Tensor Imaging (DTI), T2 weighted high resolution and T2 mapping) at several time points (pre-IR and 15, 50, 90 and 180 days post-IR). We also investigated the ability of MRI to assess the early stage effect of ionising radiation treatment on the invasiveness of an infiltrative rodent GBM model by using T2 weighted imaging. Aims of this thesis: Our research focussed on investigating a range of established and novel MRI methods as an imaging biomarkers of radiation-induced brain injury. In the future, this may help with the early identification of patients likely to later suffer from reduced cognitive functioning. It will also facilitate the identification of treatment options to address infiltration during radiotherapy, that will have the potential to improve future treatment outcomes.