Effect of the Maximum Dose on White Matter Fiber Bundles Using Longitudinal Diffusion Tensor Imaging

Abstract

Purpose: Previous efforts to decrease neurocognitive effects of radiation focused on sparing isolated cortical structures. We hypothesize that understanding temporal, spatial, and dosimetric patterns of radiation damage to whole-brain white matter (WM) after partial-brain irradiation might also be important. Therefore, we carried out a study to develop the methodology to assess radiation therapy (RT)-induced damage to whole-brain WM bundles.

Methods and materials: An atlas-based, automated WM tractography analysis was implemented to quantify longitudinal changes in indices of diffusion tensor imaging (DTI) of 22 major WM fibers in 33 patients with predominantly low-grade or benign brain tumors treated by RT. Six DTI scans per patient were performed from before RT to 18 months after RT. The DTI indices and planned doses (maximum and mean doses) were mapped onto profiles of each of 22 WM bundles. A multivariate linear regression was performed to determine the main dose effect as well as the influence of other clinical factors on longitudinal percentage changes in axial diffusivity (AD) and radial diffusivity (RD) from before RT.

Results: Among 22 fiber bundles, AD or RD changes in 12 bundles were affected significantly by doses (P<.05), as the effect was progressive over time. In 9 elongated tracts, decreased AD or RD was significantly related to maximum doses received, consistent with a serial structure. In individual bundles, AD changes were up to 11.5% at the maximum dose locations 18 months after RT. The dose effect on WM was greater in older female patients than younger male patients.

Conclusions: Our study demonstrates for the first time that the maximum dose to the elongated WM bundles causes post-RT damage in WM. Validation and correlative studies are necessary to determine the ability and impact of sparing these bundles on preserving neurocognitive function after RT.

Copyright © 2016 Elsevier Inc. All rights reserved.

Figures

Figure 1

Examples (with scalp and skull removed) of different high-dose regions of two patients who had neurocognitive declines related to the dorsolateral prefrontal cortex (DLPFC). High-dose regions were distal to the DLPFC but overlapped at different sections of the inferior fronto-occipital fasciculus (IFOF), an essential part of the DLPFC neural network.

Figure 2

Flow chart of the atlas-based, automated tractography method.

Figure 3

Heatmaps of linear fixed-effect models. The vertical axis represents dependent variables (sorted first by ΔAD%/ΔRD% then by time points). The horizontal axis depicts independent variables of four dose metrics, glioma, and three interaction co-variables. Examples of WM bundles responded to the maximum dose and to both the maximum and mean doses are displayed in (A) and (B), respectively.

Figure 4

Dose-dependent longitudinal ΔAD% and ΔRD% for the Max-Dose (left), Multi-Dose (middle) and Non-Sig group (right column). ΔAD%/ΔRD% were averaged over voxels receiving doses higher than the 95%ile on bundles for the Max-Dose and Non-Sig groups, and over all voxels for the Multi-Dose group. ΔAD%/ΔRD% in 4A and 4C were further averaged over the bundles within each group. ΔAD% (4B) and ΔRD% (4D) from the IFOF, UNC and GCC represent the three abovementioned groups. Red diamonds and green stars: significant at the time point for respective high- and medium-dose levels.