Analysing the mechanisms of microbeam-radiation therapy (MRT) on gliomas in a mouse model using innovative 3D imaging technology

• Applicant: Professor Dr. Thomas Schmid
• Subject Area: Radiology
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 459947066

In Germany around half a million people develop cancer every year. Glioblastoma multiforme is an aggressive tumor type that is characterized by a high level of radiation resistance. Due to the high resistance of glioblastoma to conventional tumor therapies, new treatment approaches are urgently needed. Microbeam radiation therapy is an innovative, but still preclinical concept in radiation oncology. Several preclinical investigations showed that this treatment concept preferentially damages the tumor tissue and it spares normal tissue more effectively than conventional radiation therapy. Therefore, microbeam radiation therapy could be an extremely promising method to selectively ablate tumors. Microbeam radiation therapy is still a new field of research and the biological mechanisms behind the microbeam radiation therapy are not yet understood. The most widely accepted hypothesis is related to differences in the sensitivity of immature tumor vasculature and mature normal tissue vasculature. Furthermore, an immunomodulatory effect is assumed for microbeam radiation therapy being capable of triggering the immune and inflammatory responses in the tumor due to high peak doses and an immunogenic cell death. Currently, such investigations are based on 2D histological sections. However, 2D imaging is usually not representative enough and insufficient to map complex vascular alterations after therapy. In this application we propose to use a highly innovative histology based 3D imaging technology with subcellular resolution and we want to combine this imaging technique with a machine learning based analysis to investigate the vascular changes, interaction with the immune system as well as changes in the oxygen supply after microbeam radiation therapy. The application of such groundbreaking 3D imaging method will provide a comprehensive and representative account of the biological processes in normal and tumor tissue of a mouse brain. Moreover, it will provide an important step to understand the effect of microbeam therapy and other spatially fractionated radiation therapy methods, which is key for their rapid clinical translation.

• DFG Programme: Research Grants
• Co-Investigator: Professorin Dr. Stephanie Combs