Regional susceptibility to dose-dependent white matter damage after brain radiotherapy

Abstract

Background and Purpose Regional differences in sensitivity to white matter damage after brain radiotherapy (RT) are not well-described. We characterized the spatial heterogeneity of dose-response across white matter tracts using diffusion tensor imaging (DTI). Materials and Methods Forty-nine patients with primary brain tumors underwent MRI with DTI before and 9–12 months after partial-brain RT. Maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were generated. Atlas-based white matter tracts were identified. A secondary analysis using skeletonized tracts was also performed. Linear mixed-model analysis of the relationship between mean and max dose and percent change in DTI metrics was performed. Results Tracts with the strongest correlation of FA change with mean dose were the fornix (−0.46 percent/Gy), cingulum bundle (−0.44 percent/Gy), and body of corpus callosum (−0.23 percent/Gy), p<.001. These tracts also showed dose-sensitive changes in MD and RD. In the skeletonized analysis, the fornix and cingulum bundle remained highly dose-sensitive. Maximum and mean dose were similarly predictive of DTI change. Conclusions The corpus callosum, cingulum bundle, and fornix show the most prominent dose-dependent changes following RT. Future studies examining correlation with cognitive functioning and potential avoidance of critical white matter regions are warranted.

Dose-dependent degeneration of non-cancerous brain tissue in post-radiotherapy patients: A diffusion tensor imaging study

“…RD is 50% more sensitive to radiation than AD in WM, meaning that diffusion becomes increasingly isotropic with a progressive dose. These finding are consistent with previous studies, confirming that the increase in RD overcomes the increase in AD [19,55]. Similarly, an increase in RD has been suggested to relate to demyelination in human [65] and animal [20] RT studies.…”

“…Regional differences appear, but it remains doubtful whether these are genuine or artefactual as previous examples pooled the bilateral regions into a single one, forcing symmetrical results [55].…”

“…Studies on tissue-dose interaction, as the current one, aid in understanding radiation-induced cognitive decline, which may be the consequence of, but not restricted to, demyelination and loss of axonal integrity with increasing radiation doses. Research in neuroscience, especially on aging [47,48] and cognitive impairment [49,50] ROIs receiving certain dose levels or aim to avoid PVE by restricting the masking to connected voxels that only include WM structure by excluding voxels with FA lower than 0.2 [17,29,55].…”

“…We further assumed that tissue change relates linearly to the applied dose. While this framework is widely applied by the RT-community [17,29,55,75], these assumptions may only approximate the true underlying relations. Further biophysical modeling is .…”

Retinal sublayer defect is independently associated with the severity of hypertensive white matter hyperintensity

“…Given the link between the retina and the brain, our findings echoes the association between the retina and the brain in WMH as previously reported in the other cerebral small vessel diseases such as Alzheimer's disease (Debette & Markus, ; Rhodius‐Meester et al, ). Although microstructural changes in the white matter have been noted for its liability to microvascular damage (Connor et al, ; Lin, Wang, Lan, & Fan, ), our study highlighted the role of neurodegeneration in the white matter damage on MRI images using the Fazekas scale; further studies on the association between the retinal vasculature and the cerebral microstructure are needed to validate this hypothesis and also evaluation of the optic nerve could be investigated. With regard to aging, we observed that increase in age was associated with thinning of the retinal layers and susceptibility to lesions in the white matter which is congruent with previous reports (Harwerth, Wheat, & Rangaswamy, ; Mutlu et al, ).…”