Microstructural Injury to Corpus Callosum and Intrahemispheric White Matter Tracts Correlate With Attention and Processing Speed Decline After Brain Radiation.

Abstract Background The corpus callosum (CC) and intra-hemispheric white matter tracts (IHWM) subserve critical aspects of attention and processing speed. We analyzed imaging biomarkers of microstructural injury within these regions and association with attention/processing speed decline post-radiotherapy in primary brain tumor patients. Methods On a prospective clinical trial, 44 primary brain tumor patients underwent cognitive testing and MRI/diffusion-weighted imaging pre-radiotherapy, and 3-, 6-, and 12-months post-radiotherapy. CC (subregions; total) and IHWM tracts (left/right without CC; total) were autosegmented; tumor/tumor bed/edema were censored. Biomarkers included: volume changes (cc); mean diffusivity (MD, higher values indicate WM injury); fractional anisotropy (FA, lower values indicate WM injury). Reliable-change indices measured changes in attention (WAIS-IV digits-forward; D-KEFS-Trail-Making visual-scanning) and processing speed (WAIS-IV coding; D-KEFS-Trail-Making number-sequencing, letter-sequencing), accounting for practice effects. Linear mixed-effects models evaluated associations between 1) mean radiation dose and biomarkers (volume, MD, FA); 2) imaging biomarkers and neurocognitive performance. Statistics were corrected for multiple comparisons. Results Processing speed declined at 6 months (number-sequencing, letter-sequencing; p Conclusions The CC demonstrated radiation dose-dependent atrophy and WM injury. Microstructural injury within the CC and IHWM was associated with attention/processing speed decline after radiotherapy. These areas represent possible avoidance regions for preservation of attention/processing speed.