title: Voxel-based analysis of T2 hyperintensities in white matter during treatment of childhood leukemia.
abstract: OBJECTIVE
  White matter (WM) hyperintensities on T2-weighted MR imaging are the most common imaging manifestation of neurotoxic effects of therapy for central nervous system (CNS) prophylaxis in childhood acute lymphoblastic leukemia (ALL). This study uses voxel-based analyses (VBA) of T2-weighted imaging of patients during treatment to identify which WM regions are preferentially damaged.
  
  
  METHODS
  Two sets of conventional T2-weighted axial images were acquired on a 1.5T MR imaging scanner from 197 consecutive patients (85 female, 112 male; aged 1.0-18.9 years) enrolled on an institutional ALL treatment protocol. Images were acquired after completion of induction therapy and after the final of the 4 courses of intravenous high-dose methotrexate in consolidation therapy (3.9 +/- 0.8 months apart). Voxel-wise statistical testing of the incremental change between normalized longitudinal T2 images was performed with radiologist reading (normal or abnormal) and treatment risk-group as covariates.
  
  
  RESULTS
  Two highly significant bilateral clusters of T2 signal intensity change were identified in both 1-group and 2-group analyses. The regions were symmetric in size, shape, and average signal intensity. Increased T2-weighted signal intensity from these regions both within and between examinations were nonlinear functions of age at examination, and the difference between the examinations was greater for older subjects who received more intense therapy.
  
  
  CONCLUSIONS
  These analyses identified specific WM tracts involving predominantly the anterior, superior, and posterior corona radiata and superior longitudinal fasciculus, which were at increased risk for the development of T2-weighted hyperintensities during therapy for childhood ALL. These vulnerable regions may be the cause of subsequent cognitive difficulties consistently observed in survivors.
authors: Division of Translational Imaging Research, St. Jude Children's Research Hospital, Memphis, TN, USA. gene.reddick@stjude.org
authors: W E
authors: WE
authors: Reddick
authors: J O
authors: JO
authors: Glass
authors: D P
authors: DP
authors: Johnson
authors: F H
authors: FH
authors: Laningham
authors: C-H
authors: CH
authors: Pui
mesh_terms: D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D001921:Brain / Q000473:pathology*; D002552:Cerebral Ventricles / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D006801:Humans; D007223:Infant; D007278:Injections, Spinal; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D010296:Parietal Lobe / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology*; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate