Differences in supratentorial white matter diffusion after radiotherapy – new biomarker of normal brain tissue damage?

Abstract

Introduction. Therapy-induced injury to normal brain tissue is a concern in the treatment of all types of brain tumours. The purpose of this study was to investigate if magnetic resonance diffusion tensor imaging (DTI) could serve as a potential biomarker for the assessment of radiation-induced long-term white matter injury. Material and methods. DTI- and T1-weighted images of the brain were obtained in 19 former radiotherapy patients [nine men and 10 women diagnosed with astrocytoma (4), pituitary adenoma (6), meningioma (8) and craniopharyngioma (1), average age 57.8 (range 35–71) years]. Average time from radiotherapy to DTI scan was 4.6 (range 2.0–7.1) years. NordicICE software (NIC) was used to calculate apparent diffusion coefficient maps (ADC-maps). The co-registration between T1 images and ADC-maps were done using the auto function in NIC. The co-registration between the T1 images and the patient dose plans were done using the auto function in the treatment planning system Eclipse from Varian. Regions of interest were drawn on the T1-weighted images in NIC based on isocurves from Eclipse. Data was analysed by t-test. Estimates are given with 95% CI. Results. A mean ADC difference of 4.6(0.3;8.9)× 10⁻⁵ mm²/s, p = 0.03 was found between paired white matter structures with a mean dose difference of 31.4 Gy. Comparing the ADC-values of the areas with highest dose from the paired data (dose > 33 Gy) with normal white matter (dose < 5 Gy) resulted in a mean dose difference of 44.1 Gy and a mean ADC difference of 7.87(3.15;12.60)× 10⁻⁵ mm²/s, p = 0.003. Following results were obtained when looking at differences between white matter mean ADC in average dose levels from 5 to 55 Gy in steps of 10 Gy with normal white matter mean ADC: 5 Gy; 1.91(−1.76;5.58)× 10⁻⁵ mm²/s, p = 0.29; 15 Gy; 5.81(1.53;10.11)× 10⁻⁵ mm²/s, p = 0.01; 25 Gy; 5.80(2.43;9.18)× 10⁻⁵ mm²/s, p = 0.002; 35 Gy; 5.93(2.89;8.97)× 10⁻⁵ mm²/s, p = 0.0007; 45 Gy; 4.32(−0.24;8.89)× 10⁻⁵ mm²/s, p = 0.06; 55 Gy; −4.04(−14.96;6.89)× 10⁻⁵ mm²/s, p = 0.39. Conclusion. The results indicate that the structural integrity of white matter, assessed by ADC-values based on DTI, undergoes changes after radiation therapy starting as early as total dose levels between 5 and 15 Gy.

Declaration of interest: Supported by CIRRO – The Lundbeck Foundation Center for Interventional Research in Radiation Oncology and The Danish Council for Strategic Research. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.