Abstract
BACKGROUND: Central nervous system (CNS) tumors are the second most common pediatric malignancy and the leading cause of cancer-related mortality in children. Although advances in therapy have improved survival, survivors experience neurocognitive decline related to tumor location, surgery, and radiation. Understanding how white matter integrity-assessed by diffusion tensor imaging (DTI)-relates to neurocognitive outcomes is essential for developing treatment-sparing strategies that preserve long-term function. METHODS: This retrospective study included 171 neurocognitive assessments and at least 2 time-matched DTI scans from 68 pediatric brain tumor patients. Healthy controls (n = 80) were drawn from the Pediatric Imaging, Neurocognition, and Genetics repository. Axial diffusivity (λ(‖)), radial diffusivity (λ(⊥)), mean diffusivity (MD), and fractional anisotropy (FA) were quantified across 168 neuroanatomical substructures. Temporal changes in DTI were modelled using linear fits, and associations with Wechsler Full Scale Intelligence Quotient (IQ), Working Memory Index (WMI), and Processing Speed Index (PSI) were analyzed using Pearson's correlation. RESULTS: Longitudinal assessment revealed median annual declines in IQ and WMI. Changes in white matter diffusivity significantly correlated with neurocognitive outcomes, particularly within the cerebellum, cerebellar and cerebral peduncles, thalamus, and corpus callosum. Increases in λ(‖) and MD were associated with declines in IQ, WMI, and PSI, while increases in FA correlated with improved WMI. CONCLUSION: Loss of white matter integrity was associated with neurocognitive decline in pediatric brain tumor survivors. These findings support the development of interventions aimed at preserving brain function and long-term quality of life by monitoring and mitigating factors associated with neurocognitive change.