Chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning in breast cancer patients

Purpose: A subgroup of patients with breast cancer suffers from mild cognitive impairment after chemotherapy. To uncover the neural substrate of these mental complaints, we examined cerebral white matter (WM) integrity after chemotherapy using magnetic resonance diffusion tensor imaging (DTI) in combination with detailed cognitive assessment. Methods: Post-chemotherapy breast cancer patients (n=17) and age matched healthy controls (n=18) were recruited for DTI and neuropsychological testing, including the self-report Cognitive Failure Questionnaire (CFQ). Differences in DTI WM integrity parameters (fractional anisotropy (FA) and mean diffusivity (MD)) between patients and controls were assessed using a voxel-based two-sample-T-test. An additional control group of non-chemotherapy-treated breast cancer patients (n=10) was added as validation. To address the heterogeneity observed in cognitive function after chemotherapy, we performed a voxel-based correlation analysis between FA values and individual neuropsychological test scores. Results: In comparison with healthy controls, the chemotherapy-treated patient group demonstrated decreased FA in frontal WM (p<0.0001) and temporal WM (p<0.01) tracts and increased MD in frontal WM (p