Whole-brain radiotherapy associated with structural changes resembling aging as determined by anatomic surface-based deep learning

Abstract

Background Brain metastases are the most common intracranial tumors in adults and are associated with significant morbidity and mortality. Whole brain radiotherapy (WBRT) is used frequently in patients for palliation, but can result in neurocognitive deficits. While dose-dependent injury to individual areas such as the hippocampus have been demonstrated, global structural shape changes after WBRT remain to be studied. Methods We studied healthy controls and patients with brain metastases and examined MRI brain anatomic surface data before and after WBRT. We implemented a validated graph convolutional neural network model to estimate patient’s “brain age”. We further developed a mixed-effects linear model to compare estimated age of whole brain and substructures before and after WBRT. Results 4220 subjects were analyzed (4148 healthy controls and 72 patients). Median radiation dose was 30Gy (range 25 – 37.5Gy). The whole brain and substructures underwent structural change resembling rapid aging in radiated patients compared to healthy controls; the whole brain “aged” 9.32 times faster, the cortex 8.05 times faster, the subcortical structures 12.57 times faster, and the hippocampus 10.14 times faster. In a subset analysis, the hippocampus “aged” 8.88 times faster in patients after conventional WBRT versus after hippocampal avoidance (HA)-WBRT. Conclusions Our findings suggest that WBRT causes the brain and its substructures to undergo structural changes at a pace up to 13x of the normal aging pace, where hippocampal avoidance offers focal structural protection. Correlating these structural imaging changes with neurocognitive outcomes following WBRT or HA-WBRT would benefit from future analysis.