Abstract
To investigate radiation therapy-induced microstructural damage of white matter in patients with high-grade glioma by diffusion tensor imaging (DTI). DTI was performed in 18 patients with high-grade glioma (WHO grades III and IV) and 13 healthy controls. DTI images were cross-sectionally aligned for the calculation of baseline fractional anisotropy (FA). Interhemispheric FA values in patients with high-grade glioma before or without brain radiation therapy were compared with the interhemispheric FA values in patients after radiation therapy and in healthy controls. In a subgroup without any clinical or diagnostic evidence of tumor progression, serial DTI data (5-11 scans) before and after radiation therapy were collected and longitudinal interhemispheric FA changes were assessed and compared to longitudinal data from the control group.In addition, interhemispheric axial, mean, and radial diffusivity was assessed. Global interhemispheric FA reductions could be detected cross-sectionally in patients after radiation therapy; these were significantly different from global interhemispheric FA differences both in patients without radiation and in healthy controls. Longitudinal scans in patients with radiation therapy confirmed these findings and revealed progressive microstructural white matter damage after partial brain radiotherapy. The additional DTI metrics axial diffusion, mean diffusivity, and radial diffusion confirmed interhemispheric differences in patients without or before radiation therapy, which were lower than the differences in patients after radiation therapy, although not reaching significance. Interhemispheric global FA differences could potentially serve as a biological marker for irradiation-induced microstructural white matter damage.
Highlights
High-grade glioma, including glioblastoma as the most common primary brain tumor, account for approximately 25% of all central nervous system tumors
We aim to identify microstructural changes only due to radiation therapy by the analysis of peritumoral fractional anisotropy (FA) values [15, 16] and how they proceed over time, i.e., patients with any signs of tumor progression were not included in the study
The changes over time in hemispherically averaged FA values were visualized (Figure 3C). This neuroimaging study aimed to investigate via diffusion tensor imaging (DTI) whether partial brain radiation therapy induces alterations of white matter integrity and how these potential alterations might progress over time
Summary
High-grade glioma, including glioblastoma as the most common primary brain tumor, account for approximately 25% of all central nervous system tumors. Central nervous system dysfunction is assumed to be due to early irradiation-induced inflammation as well as loss of brain structural integrity The latter might be associated with chronic inflammation and degradation of progenitor cell niche, which potentially causes progressive neuronal loss and, could explain longterm cerebral dysfunction after radiation therapy [7, 8]. The assessment of this damage with routine neuroimaging tools is limited, whereas diffusion tensor imaging (DTI) allows for the analysis of the structural connectivity and has already shown to be a non-invasive tool to probe white matter integrity, identifying white matter microstructural changes at a higher sensitivity than by T1- and T2-weighted magnetic resonance imaging (MRI) [9]. We used cross-sectional and longitudinal DTI measurements to calculate FA, AD, MD, and RD differences, thereby enabling us to individually screen the possible damage to the structural integrity of the brain over time
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