Correlation Between Neurocognitive Outcomes and Neuroaxonal Connectome Alterations After Whole Brain Radiotherapy: A Proof-of-Concept Study

<b>Background/Objectives:</b> Connectomics is an evolving branch of neuroscience that determines structural and functional connectivity in the brain. The objective of this prospective imaging study is to evaluate the effect of whole brain radiotherapy (WBRT) on the connectome. <b>Methods:</b> A combination of diffusion tensor imaging (DTI) and functional magnetic resonance imaging (<i>f</i>MRI) was used to study the structural and functional connectivity of the brain, and a machine learning algorithm trained to analyze subject-specific data was applied to create individualized brain maps with 15 neuronal networks for each patient. These brain maps were compared to normal brains from the human connectome project, producing an anomaly matrix. Connectome analysis and multi-dimensional neurocognitive testing on a web-based platform were performed at baseline and 3 months post-WBRT. The change in anomaly frequency was co-related with neurocognitive outcomes. <b>Results:</b> At baseline, connectome analysis revealed that the multiple demand network had the most anomalies (46%). Pre- and post-WBRT comparison revealed increases in proportional anomaly frequency across multiple networks. Pearson correlation showed correlation between neurocognitive domain decline and anomaly changes: learning and memory domain with subcortical network [Verbal recall (Pearson coefficient -0.94; <i>p</i> < 0.01), verbal revision (Pearson coefficient -0.89; <i>p</i> = 0.01), and verbal recognition (Pearson coefficient -0.94; <i>p</i> < 0.01)]. <b>Conclusions:</b> This proof-of-concept study integrated data from DTI and <i>f</i>MRI in the form of connectome and revealed significant changes in brain connectivity, with WBRT that also correlated with neurocognitive outcomes. Further studies in a larger cohort are underway, and correlations with white matter changes and tumor locations/numbers will be performed.