title: Hypercellularity Components of Glioblastoma Identified by High b-Value Diffusion-Weighted Imaging.
abstract: OBJECTIVE
  Use of conventional magnetic resonance imaging (MRI) for target definition may expose glioblastomas (GB) to inadequate radiation dose coverage of the nonenhanced hypercellular subvolume. This study aimed to develop a technique to identify the hypercellular components of GB by using high b-value diffusion-weighted imaging (DWI) and to investigate its relationship with the prescribed 95% isodose volume (PDV) and progression-free survival (PFS).
  
  
  METHODS
  Twenty-one patients with GB underwent chemoradiation therapy post-resection and biopsy. Radiation therapy (RT) treatment planning was based upon conventional MRI. Pre-RT DWIs were acquired in 3 orthogonal directions with b-values of 0, 1000, and 3000 s/mm(2). Hypercellularity volume (HCV) was defined on the high b-value (3000 s/mm(2)) DWI by a threshold method. Nonenhanced signified regions not covered by the Gd-enhanced gross tumor volume (GTV-Gd) on T1-weighted images. The PDV was used to evaluate spatial coverage of the HCV by the dose plan. Association between HCV and PFS or other clinical covariates were assessed using univariate proportional hazards regression models.
  
  
  RESULTS
  HCVs and nonenhanced HCVs varied from 0.58 to 67 cm(3) (median: 9.8 cm(3)) and 0.15 to 60 cm(3) (median: 2.5 cm(3)), respectively. Fourteen patients had incomplete dose coverage of the HCV, 6 of whom had >1 cm(3) HCV missed by the 95% PDV (range: 1.01-25.4 cm(3)). Of the 15 patients who progressed, 5 progressed earlier, within 6 months post-RT, and 10 patients afterward. Pre-RT HCVs within recurrent GTVs-Gd were 78% (range: 65%-89%) for the 5 earliest progressions but lower, 53% (range: 0%-85%), for the later progressions. HCV and nonenhanced HCV were significant negative prognostic indicators for PFS (P<.002 and P<.01, respectively). The hypercellularity subvolume not covered by the 95% PDV was a significant negative predictor for PFS (P<.05).
  
  
  CONCLUSIONS
  High b-value DWI identifies the hypercellular components of GB and could aid in RT target volume definition. Future studies will allow us to investigate the role of high b-value DWI in identifying radiation boost volumes and diagnosing progression.
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Priyanka P
authors.initials: PP
authors.lastname: Pramanik
authors.affiliation: Department of Radiology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Hemant A
authors.initials: HA
authors.lastname: Parmar
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Aaron G
authors.initials: AG
authors.lastname: Mammoser
authors.affiliation: Department of Neurology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Larry R
authors.initials: LR
authors.lastname: Junck
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Christina I
authors.initials: CI
authors.lastname: Tsien
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Lawrence
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan; Department of Radiology, University of Michigan, Ann Arbor, Michigan; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan. Electronic address: yuecao@med.umich.edu.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001929:Brain Edema / Q000175:diagnosis; D001932:Brain Neoplasms / Q000473:pathology* / Q000628:therapy; D059248:Chemoradiotherapy / Q000379:methods; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004058:Diffusion; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000473:pathology* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D000077204:Temozolomide; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide