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 9-12months 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.

Keywords: Diffusion tensor imaging; Dose-dependent; Radiation; Radiotherapy; White matter.

Conflict of interest statement

Conflict of Interest Statement:

Dr. Hattangadi-Gluth has a research grant from Varian Medical Systems, unrelated to the current study. Dr. Dale receives funding through research agreements with General Electric Healthcare, and Medtronic, unrelated to the current study. Dr. Moiseenko reports prior honorarium and travel fees from Varian Medical Systems for a talk outside the submitted work.

Copyright © 2017 Elsevier B.V. All rights reserved.

Figures

Fig 1

Representative JHU ICBM-DTI-81 white-matter atlas labels overlaid on our cohort’s mean FA image and mean FA skeleton. GeCC, genu of corpus callosum; ACR, anterior corona radiata; AIC, anterior limb of internal capsule; PIC, posterior limb of internal capsule; RIC, rentrolenticular part of internal capsule; PTR, posterior thalamic radiation; SpCC, splenium of corpus callosum; Tp, tapetum; FcSt, fornix (cres)/stria terminalis; EC, external capsule; SLF, superior longitudinal fasciculus; Cb, cingulum bundle ; F, fornix (column and body of fornix); SS, sagittal stratum; Cp, cingulum (parahippocampal); PCR, posterior corona radiate; SFOF, superior fronto-occipital fasciculus; BCC, body of corpus callosum; SCR, superior corona radiata. Note: uncinate fasciculus and corticospinal tracts not shown.

Fig 2

Linear mixed model coefficients; whole ROI analysis. Vertical ticks represent percent change per Gy. Shaded widths are 95% confidence intervals adjusted for multiple comparisons. Statistical significance (p<.05 bonferroni adjusted for n="21)" is color-coded. solid lines are correlations with mean dose dashed maximum dose.>

Fig 3

Linear mixed model coefficients; skeletonized tract analysis. Vertical ticks represent percent change per Gy. Shaded widths are 95% confidence intervals adjusted for multiple comparisons. Statistical significance (p<.05 bonferroni adjusted for n="21)" is color-coded. solid lines are correlations with mean dose dashed maximum dose.>

Fig 4

Regional sensitivity to radiation. Tracts are filled with their corresponding coefficient for percent change in FA (from the model correlating mean dose to changes in the whole atlas ROI) and color coded according to value. Only statistically significant coefficients are shown. The signs for coefficients are flipped, i.e. FA is expected to decrease, so greater decreases in FA are represented by positive numbers and intensifying red color.