Characterization of brain response following cranial radiotherapy

Cranial radiotherapy (CRT) is a vital component for the treatment of pediatric brain tumors, with combination therapy that includes CRT resulting in almost 90\% five-year survival. However, survivors treated with CRT exhibit alterations in brain development and long-term deficits in brain structure and function. Clinical and pre-clinical studies have identified that the response to CRT is multifaceted in the developing brain, but the contribution of these parts and their evolution over time in the context of brain development remain unclear. In this thesis, I investigated treatment response in the developing brain following CRT and then manipulated response to investigate mechanism in mice. First, volume changes across the brain shortly following CRT were characterized by magnetic resonance imaging, demonstrating differences in the timing of volume changes in gray and white matter. Next, the relationship between CRT-induced volume changes and underlying cellular changes was investigated quantitatively with serial two-photon tomography, mapping cellular density across the brain with and without exposure to CRT. Finally, investigation of the brain's innate immune system in CRT-induced changes demonstrated that the presence of microglia is tightly linked to brain volume. Manipulation of the inflammatory response by modulation of microglia number had different effects on neuroanatomical outcome depending on sex. These studies provide a foundation for future research aimed at developing interventions to mitigate long-term neurocognitive deficits in survivors of pediatric cancer.

Department dc:contributor.department

Medical Biophysics

Year dc:date.issued

2024

Author dc:creator

• Ayoub, Ramy

Advisor dc:contributor.advisor

• Nieman, Brian J

• brain development
• magnetic resonance imaging
• mouse imaging
• neuro-oncology
• normal tissue toxicity

Handle dc:identifier.uri

http://hdl.handle.net/1807/140146

OAI identifier oai:identifier

oai:utoronto.scholaris.ca:1807/140146