Radiation-Induced Changes in Normal-Appearing White Matter in Patients With Cerebral Tumors: A Diffusion Tensor Imaging Study

Purpose: To quantify the radiation-induced changes in normal-appearing white matter before, during, and after radiotherapy (RT) in cerebral tumor patients. Methods and Materials: Twenty-five patients with low-grade glioma, high-grade glioma, or benign tumor treated with RT were studied using diffusion tensor magnetic resonance imaging. The biologically corrected doses ranged from 50 to 81 Gy. The temporal changes were assessed before, during, and to 45 weeks after the start of RT. The mean diffusivity of water (<D>), fractional anisotropy of diffusion, diffusivity perpendicular (λ_⊥) and parallel (λ_{{norm of matrix}}) to white matter fibers were calculated in normal-appearing genu and splenium of the corpus callosum. Results: In the genu and splenium, fractional anisotropy decreased and <D>, λ_{{norm of matrix}}, λ_⊥ increased linearly and significantly with time (p < 0.01). At 45 weeks after the start of RT, λ_⊥ had increased ∼30% in the genu and splenium, and λ_{{norm of matrix}} had increased 5% in the genu and 9% in the splenium, suggesting that demyelination is predominant. The increases in λ_⊥ and λ_{{norm of matrix}} were dose dependent, starting at 3 weeks and continuing to 32 weeks from the start of RT. The dose-dependent increase in λ_⊥ and λ_{{norm of matrix}} was not sustained after 32 weeks, indicating the transition from focal to diffuse effects. Conclusion: The acute and subacute changes in normal-appearing white matter fibers indicate radiation-induced demyelination and mild structural degradation of axonal fibers. The structural changes after RT are progressive, with early dose-dependent demyelination and subsequent diffuse dose-independent demyelination and mild axonal degradation. Diffusion tensor magnetic resonance imaging is potentially a biomarker for the assessment of radiation-induced white matter injury.