title: Brain tumor therapy-induced changes in normal-appearing brainstem measured with longitudinal diffusion tensor imaging.
abstract: OBJECTIVE
  To characterize therapy-induced changes in normal-appearing brainstems of childhood brain tumor patients by serial diffusion tensor imaging (DTI).
  
  
  METHODS
  We analyzed 109 DTI studies from 20 brain tumor patients, aged 4 to 23 years, with normal-appearing brainstems included in the treatment fields. Those with medulloblastomas, supratentorial primitive neuroectodermal tumors, and atypical teratoid rhabdoid tumors (n = 10) received postoperative craniospinal irradiation (23.4-39.6 Gy) and a cumulative dose of 55.8 Gy to the primary site, followed by four cycles of high-dose chemotherapy. Patients with high-grade gliomas (n = 10) received erlotinib during and after irradiation (54-59.4 Gy). Parametric maps of fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were computed and spatially registered to three-dimensional radiation dose data. Volumes of interest included corticospinal tracts, medial lemnisci, and the pons. Serving as an age-related benchmark for comparison, 37 DTI studies from 20 healthy volunteers, aged 6 to 25 years, were included in the analysis.
  
  
  RESULTS
  The median DTI follow-up time was 3.5 years (range, 1.6-5.0 years). The median mean dose to the pons was 56 Gy (range, 7-59 Gy). Three patterns were seen in longitudinal FA and apparent diffusion coefficient changes: (1) a stable or normal developing time trend, (2) initial deviation from normal with subsequent recovery, and (3) progressive deviation without evidence of complete recovery. The maximal decline in FA often occurred 1.5 to 3.5 years after the start of radiation therapy. A full recovery time trend could be observed within 4 years. Patients with incomplete recovery often had a larger decline in FA within the first year. Radiation dose alone did not predict long-term recovery patterns.
  
  
  CONCLUSIONS
  Variations existed among individual patients after therapy in longitudinal evolution of brainstem white matter injury and recovery. Early response in brainstem anisotropy may serve as an indicator of the recovery time trend over 5 years after radiation therapy.
authors.affiliation: Department of Radiological Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA. Chia-Ho.Hua@stjude.org
authors.forename: Chiaho
authors.initials: C
authors.lastname: Hua
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Merchant
authors.forename: Amar
authors.initials: A
authors.lastname: Gajjar
authors.forename: Alberto
authors.initials: A
authors.lastname: Broniscer
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yimei
authors.initials: Y
authors.lastname: Li
authors.forename: George R
authors.initials: GR
authors.lastname: Glenn
authors.forename: Larry E
authors.initials: LE
authors.lastname: Kun
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ogg
mesh_terms: D000293:Adolescent; D001932:Brain Neoplasms / Q000532:radiotherapy*; D001933:Brain Stem / Q000473:pathology / Q000528:radiation effects*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D005910:Glioma / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008527:Medulloblastoma / Q000473:pathology / Q000532:radiotherapy; D018242:Neuroectodermal Tumors, Primitive / Q000473:pathology / Q000601:surgery; D011149:Pons / Q000528:radiation effects; D011832:Radiation Injuries / Q000473:pathology*; D012189:Retrospective Studies; D018335:Rhabdoid Tumor / Q000473:pathology / Q000601:surgery; D055815:Young Adult