Abstract
BACKGROUND
Curative treatments for medulloblastoma impart significant toxicity on the developing brain. Though treatment-related changes to the white matter connections have been described, there remains a limited understanding of treatment effect on the structural connectome: the dense, integrative network of white matter connections present in the brain. The connectome is thought to subserve complex and dynamic behaviors, therefore identifying areas of compromise within the connectome may help elucidate the mechanisms of toxicity common among medulloblastoma survivors. METHODS AND
RESULTS
Magnetic resonance images were acquired for 12 medulloblastoma survivors and 13 age and gender-matched children using a Siemens 3-Tesla scanner at the Hospital for Sick Children in Toronto. Post-processing of MR images was completed using FreeSurfer and MRtrix3 software. Probabilistic streamlines were generated and used to estimate whole-brain structural connectivity matrices based on the length of white matter connections. Mass univariate testing of all white matter connections (FDR = 0.05) showed significantly shorter connections in survivors (p < 0.0001). Global connectivity metrics were also analyzed; we observed significantly longer path lengths in patients (p = 0.02) but no significant differences in clustering (p = 0.99) or small-worldness (p = 0.98). These results suggest perturbed inter-regional connectivity but spared local connectivity in medulloblastoma survivors.
CONCLUSIONS
Treatment of medulloblastoma may disrupt inter-regional connectivity between distant brain regions. Future work will aim to identify the regions most affected by perturbed inter-regional connectivity, and to relate pertuberance along those connections to neuropsychological outcome in medulloblastoma survivors.