title: Association between tumor architecture derived from generalized Q-space MRI and survival in glioblastoma.
abstract: While it is recognized that the overall resistance of glioblastoma to treatment may be related to intra-tumor patterns of structural heterogeneity, imaging methods to assess such patterns remain rudimentary.
  
  
  METHODS
  We utilized a generalized Q-space imaging (GQI) algorithm to analyze magnetic resonance imaging (MRI) derived from a rodent model of glioblastoma and 2 clinical datasets to correlate GQI, histology, and survival.
  
  
  RESULTS
  In a rodent glioblastoma model, GQI demonstrated a poorly coherent core region, consisting of diffusion tracts <5 mm, surrounded by a shell of highly coherent diffusion tracts, 6-25 mm. Histologically, the core region possessed a high degree of necrosis, whereas the shell consisted of organized sheets of anaplastic cells with elevated mitotic index. These attributes define tumor architecture as the macroscopic organization of variably aligned tumor cells. Applied to MRI data from The Cancer Imaging Atlas (TCGA), the core-shell diffusion tract-length ratio (c/s ratio) correlated linearly with necrosis, which, in turn, was inversely associated with survival (p = 0.00002). We confirmed in an independent cohort of patients (n = 62) that the c/s ratio correlated inversely with survival (p = 0.0004).
  
  
  CONCLUSIONS
  The analysis of MR images by GQI affords insight into tumor architectural patterns in glioblastoma that correlate with biological heterogeneity and clinical outcome.
authors.affiliation: Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA.
authors.forename: Erik N
authors.initials: EN
authors.lastname: Taylor
authors.affiliation: Radiation Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yao
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Cheah
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA.|Department of Engineering Science, University of Oxford, Oxford, UK.
authors.forename: Phillip
authors.initials: P
authors.lastname: Alexander
authors.affiliation: Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA.
authors.forename: Leon
authors.initials: L
authors.lastname: Lin
authors.affiliation: Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA.
authors.forename: George E
authors.initials: GE
authors.lastname: Aninwene
authors.affiliation: Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Hoffman
authors.affiliation: Radiation Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Mahajan
authors.affiliation: Radiation Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Abdallah S R
authors.initials: ASR
authors.lastname: Mohamed
authors.affiliation: Department of Radiology, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: McDannold
authors.affiliation: Radiation Oncology, University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Clifton D
authors.initials: CD
authors.lastname: Fuller
authors.affiliation: Center for Theoretical and Applied Neuro-Oncology and Department of Neurosurgery, University of California, San Diego, CA, USA.
authors.forename: Clark C
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gilbert
mesh_terms: D000465:Algorithms; D000818:Animals; D014408:Biomarkers, Tumor; D001921:Brain / Q000473:pathology*; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality*; D004195:Disease Models, Animal; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009336:Necrosis / Q000473:pathology; D011379:Prognosis; D051381:Rats; D015203:Reproducibility of Results
chemical_list: D014408:Biomarkers, Tumor
keywords: cancer biomarkers; diffusion weighted MRI; glioma