title: Diffusion tensor imaging of normal-appearing white matter as biomarker for radiation-induced late delayed cognitive decline.
abstract: OBJECTIVE
  To determine whether early assessment of cerebral white matter degradation can predict late delayed cognitive decline after radiotherapy (RT).
  
  
  METHODS
  Ten patients undergoing conformal fractionated brain RT participated in a prospective diffusion tensor magnetic resonance imaging study. Magnetic resonance imaging studies were acquired before RT, at 3 and 6 weeks during RT, and 10, 30, and 78 weeks after starting RT. The diffusivity variables in the parahippocampal cingulum bundle and temporal lobe white matter were computed. A quality-of-life survey and neurocognitive function tests were administered before and after RT at the magnetic resonance imaging follow-up visits.
  
  
  RESULTS
  In both structures, longitudinal diffusivity (λ(‖)) decreased and perpendicular diffusivity (λ(⊥)) increased after RT, with early changes correlating to later changes (p < .05). The radiation dose correlated with an increase in cingulum λ(⊥) at 3 weeks, and patients with >50% of cingula volume receiving >12 Gy had a greater increase in λ(⊥) at 3 and 6 weeks (p < .05). The post-RT changes in verbal recall scores correlated linearly with the late changes in cingulum λ(‖) (30 weeks, p < .02). Using receiver operating characteristic curves, early cingulum λ(‖) changes predicted for post-RT changes in verbal recall scores (3 and 6 weeks, p < .05). The neurocognitive test scores correlated significantly with the quality-of-life survey results.
  
  
  CONCLUSIONS
  The correlation between early diffusivity changes in the parahippocampal cingulum and the late decline in verbal recall suggests that diffusion tensor imaging might be useful as a biomarker for predicting late delayed cognitive decline.
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, USA. chchap@umich.edu
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Chapman
authors.forename: Vijaya
authors.initials: V
authors.lastname: Nagesh
authors.forename: Pia C
authors.initials: PC
authors.lastname: Sundgren
authors.forename: Henry
authors.initials: H
authors.lastname: Buchtel
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Chenevert
authors.forename: Larry
authors.initials: L
authors.lastname: Junck
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Lawrence
authors.forename: Christina I
authors.initials: CI
authors.lastname: Tsien
authors.forename: Yue
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000328:Adult; D003072:Cognition Disorders / Q000175:diagnosis*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D006624:Hippocampus / Q000473:pathology / Q000528:radiation effects*; D006801:Humans; D008297:Male; D011939:Mental Recall / Q000528:radiation effects; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D011832:Radiation Injuries / Q000175:diagnosis* / Q000473:pathology; D011879:Radiotherapy Dosage; D013702:Temporal Lobe / Q000473:pathology / Q000528:radiation effects*; D013997:Time Factors