Radiotherapy is an essential and life-saving treatment for many patients with brain tumors, but it often leads to long-term side effects like reduced memory function, affecting their quality of life. These effects arise from injury to brain structures like the hippocampus, a main learning and memory center in the brain. This injury is caused by neuroinflammation triggered by radiotherapy. Currently, the main tools for studying this inflammation in mice requires invasive methods that can only be performed once per animal, making it difficult to study how brain injury evolves over time or how best to protect the brain from these effects. 

An emerging ultra-rapid form of radiotherapy known as FLASH, hundreds of times faster than conventional radiotherapy, has shown compelling promise in reducing damage to normal tissues without compromising tumor killing by multiple independent research groups studying multiple organ systems. In the brain, it has been shown to protect the neurons in the hippocampus and reduce or eliminate the memory impairment caused by conventional radiotherapy. This appears to be because FLASH produces less neuroinflammation. However, our ability to study this phenomenon is limited by the current tools that do not allow studying neuroinflammation in the same animals over time, and require large number of animals each evaluated at different time points. This project aims to test a new approach to safely and repeatedly monitoring brain inflammation in the same subjects over time, after conventional radiotherapy or FLASH, using advanced molecular imaging.

This is a new collaboration between the James Lab in the Department of Radiology that has developed novel molecular imaging approaches (including new positron emission tomography [PET] tracers being translated towards clinical use in patients) for visualizing immune cells in the brain that are responsible for inflammation, and the Loo Lab in the Department of Radiation Oncology that specializes in studying FLASH in preclinical models and is developing technologies for translating it towards human therapy. The PET imaging tracers developed by the James Lab help visualize the activity of immune cells in the brain, and how that activity changes with different therapies. We aim to use this to identify the optimal way of delivering FLASH for the safest treatment of brain tumors in patients.

This is an interdisciplinary initiative integrating expertise in clinical radiotherapy, radiation physics, neurobiology, and molecular imaging that establishes a new framework for evaluating the safety of brain radiotherapy. Our goal is to guide the development of safer radiotherapy and other therapies designed to protect brain function while maintaining effective cancer treatment.