paediatrics Brussels 17

RadiationOncology International Journal of biology physics

www.redjournal.org

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, y Biostatistics, and z Oncology, 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.

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 (1) . Because of the 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.

Introduction

Therapy-induced injury to the normal brainstem is a concern in the treatment of common childhood brain tumors. Injury to 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: jinsoo.uh@ stjude.org

Int J Radiation Oncol Biol Phys, Vol. 86, No. 2, pp. 292 e 297, 2013 0360-3016/$ - see front matter 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ijrobp.2013.01.028