Late radiation injuries after proton therapy in the brain
Project leaders:
Dr. Antje Dietrich (OncoRay, Dresden), antje.dietrich(at)uniklinikum-dresden.de
Dr. Emanuel Bahn (DKFZ Heidelberg), e.bahn(at)dkfz-heidelberg.de
Funded since: May 2020 - mid of 2023
Radiation-induced brain injury is a frequent observation in brain tumor patients, which ranges from cognitive deficits to the appearance of necrosis in the white matter, commonly occurring after latent periods of many months to several years. The understanding of the underlying mechanisms is still incomplete.
In recent years, findings from clinical proton therapy centers worldwide–including Heidelberg and Dresden–have indicated that the occurrence of these late radiation effects frequently collocates with two important features: regions adjacent to the brain ventricular system and regions of high linear energy transfer (LET) radiation with an increased relative biological effectiveness (RBE). The proposed research project aims to clarify the role of two postulated leading causes of late radiation effects in the brain: varying regional radiation sensitivity and the RBE variability of proton radiation. Separating the contributions of these two potential effects is of uttermost importance but challenging. In particular, definitive conclusions cannot be inferred from analysis of clinical patient data.
In Dresden, we have established a mouse model to mirror the above-described post-radiotherapy MRI image changes after targeting a sub-volume of the mouse brain using image-guided proton irradiation. In contrast to whole- or half-brain irradiation, damage and induced effects are locally confined to the targeted sub-volume in our model, reflecting the clinical situation. The aim of this joint project is to utilize this preclinical model to better understand the underlying mechanisms of radiation-induced brain injury and their correlation with physical parameters like dose and LET, as well as the influence of regional sensitivity. We combine automated image-analyses of individual cells (e.g. microglia, astrocytes, neurons) in whole-brain histological slices with calculated dose distributions and MRI changes enabling quantitative and spatial analyses of neuroinflammation and DNA repair.
