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Clinical Investigation: Pediatric Cancer
Differences in Brainstem Fiber Tract Response to
Radiation: A Longitudinal Diffusion Tensor Imaging Study
Jinsoo Uh, PhD,* Thomas E. Merchant, DO, PhD,* Yimei Li, PhD, y Tianshu Feng, MS,y
Amar Gajjar, MD,z Robert J. Ogg, PhD, * and Chiaho Hua, PhD*
Departments of *Radiological Sciences, yBiostatistics, and zOncology, St. Jude Children’s Research Hospital,
Memphis, Tennessee
Received Sep 28, 2012, and in revised form Jan 17, 2013. Accepted for publication Jan 25, 2013
Summary
Longitudinal diffusion tensor
imaging data from 42
medulloblastoma patients
were analyzed to assess
regional differences in
structural integrity changes
of brainstem white matter
tracts after radiation therapy.
These changes were not
uniform across the brainstem
despite similarities in the
distribution of dose,
suggesting that the radiation-
induced changes in
brainstem may be tract
dependent.
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 radi-
ation 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
uniformacross the brainstemafter radiation therapy. These results support a role for tract-based assess-
ment in radiation treatment planning and determination of brainstem tolerance. 2013 Elsevier Inc.
Introduction
Therapy-induced injury to the normal brainstem is a concern in
the treatment of common childhood brain tumors. Injury to the
brainstem may cause deficits in motor and sensory capabilities and
coordination functions, which can compromise the quality of life
of long-term survivors.
Current data on brainstem toxicity are limited and are based
on subjective or categoric scoring methods . Because of the
Reprint requests to: Jinsoo Uh, PhD, Department of Radiological
Sciences, St. Jude Children’s Research Hospital, 262 Danny Thomas
Place, Memphis, TN 38105. Tel: (901) 595-6545; E-mail:
Presented in part at the 2012 American Association of Physicists in
Medicine annual meeting in Charlotte, North Carolina July 29 - August 2,
2012.
Supported in part by the funding from the American Lebanese Syrian
Associated Charities and NIH R01 grant HD049888.
Conflict of interest: none.
Int J Radiation Oncol Biol Phys, Vol. 86, No. 2, pp. 292e297, 2013
0360-3016/$ - see front matter 2013 Elsevier Inc. All rights reserved.
RadiationOncology
International Journal of
biology physics