Diffusion tensor imaging of normal-appearing white matter as biomarker for radiation-induced late delayed cognitive decline

Purpose: To determine whether early assessment of cerebral white matter degradation can predict late delayed cognitive decline after radiotherapy (RT). Methods and Materials: Ten patients undergoing conformal fractionated brain RT participated in a prospective diffusion tensor magnetic resonance imaging study. Magnetic resonance imaging studies were acquired before RT, at 3 and 6 weeks during RT, and 10, 30, and 78 weeks after starting RT. The diffusivity variables in the parahippocampal cingulum bundle and temporal lobe white matter were computed. A quality-of-life survey and neurocognitive function tests were administered before and after RT at the magnetic resonance imaging follow-up visits. Results: In both structures, longitudinal diffusivity (λ _∥) decreased and perpendicular diffusivity (λ _⊥) increased after RT, with early changes correlating to later changes (p < .05). The radiation dose correlated with an increase in cingulum λ _⊥ at 3 weeks, and patients with >50% of cingula volume receiving >12 Gy had a greater increase in λ _⊥ at 3 and 6 weeks (p < .05). The post-RT changes in verbal recall scores correlated linearly with the late changes in cingulum λ _∥ (30 weeks, p < .02). Using receiver operating characteristic curves, early cingulum λ _∥ changes predicted for post-RT changes in verbal recall scores (3 and 6 weeks, p < .05). The neurocognitive test scores correlated significantly with the quality-of-life survey results. Conclusions: The correlation between early diffusivity changes in the parahippocampal cingulum and the late decline in verbal recall suggests that diffusion tensor imaging might be useful as a biomarker for predicting late delayed cognitive decline.