Differences in brainstem fiber tract response to radiation: a longitudinal diffusion tensor imaging study

Abstract

Purpose: To determine whether radiation-induced changes in white matter tracts are uniform across the brainstem.

Methods and materials: We analyzed serial diffusion tensor imaging data, acquired before radiation therapy and over 48 to 72 months of follow-up, from 42 pediatric patients (age 6-20 years) with medulloblastoma. FSL software (FMRIB, Oxford, UK) was used to calculate fractional anisotropy (FA) and axial, radial, and mean diffusivities. For a consistent identification of volumes of interest (VOIs), the parametric maps of each patient were transformed to a standard brain space (MNI152), on which we identified VOIs including corticospinal tract (CST), medial lemniscus (ML), transverse pontine fiber (TPF), and middle cerebellar peduncle (MCP) at the level of pons. Temporal changes of DTI parameters in VOIs were compared using a linear mixed effect model.

Results: Radiation-induced white matter injury was marked by a decline in FA after treatment. The decline was often accompanied by decreased axial diffusivity, increased radial diffusivity, or both. This implied axonal damage and demyelination. We observed that the magnitude of the changes was not always uniform across substructures of the brainstem. Specifically, the changes in DTI parameters for TPF were more pronounced than in other regions (P<.001 for FA) despite similarities in the distribution of dose. We did not find a significant difference among CST, ML, and MCP in these patients (P>.093 for all parameters).

Conclusions: Changes in the structural integrity of white matter tracts, assessed by DTI, were not uniform across the brainstem after radiation therapy. These results support a role for tract-based assessment in radiation treatment planning and determination of brainstem tolerance.

Figure 1

VOIs drawn on the standard color-coded FA map. (a,b) Sagittal and coronal views of midbrain and pons showing cranial-caudal locations of VOIs. (c,d) Axial views of midbrain and pons. (e) Sub-structures within brainstem.

Figure 2

Average doses in the VOIs over the 42 patients. The error bars indicate standard deviation.

Figure 3

FA maps of a medulloblastoma patient (male, baseline age 11 years) acquired at baseline (a) and the two follow-up times of 18 months (b) and 45 months (c) from baseline. The white arrows indicate dTPF showing more pronounced FA reduction than the other regions.

Figure 4

Temporal plots of FA in CST and dTPF for all 42 patients. Each FA value was normalized by the corresponding baseline value.

Figure 5

Pair-wise statistical comparison of the temporal changes of DTI parameters between pairs of VOIs. The number in the ordinate is β₃ in the statistical model equation (see the text) which indicates the temporal change of the VOI in numerator with respect to the one in denominator. The error bars indicate standard error.