title: Validation of functional diffusion maps (fDMs) as a biomarker for human glioma cellularity.
abstract: OBJECTIVE
  To present comprehensive examinations of the assumptions made in functional diffusion map (fDM) analyses and provide a biological basis for fDM classification.
  
  
  METHODS
  Sixty-nine patients with gliomas were enrolled in this study. To determine the sensitivity of apparent diffusion coefficients (ADCs) to cellularity, cell density from stereotactic biopsy specimens was correlated with preoperative ADC maps. For definition of ADC thresholds used for fDMs, the 95% confidence intervals (CI) for changes in voxel-wise ADC measurements in normal appearing tissue was analyzed. The sensitivity and specificity to progressing disease was examined using both radiographic and neurological criteria.
  
  
  RESULTS
  Results support the hypothesis that ADC is inversely proportional to cell density with a sensitivity of 1.01 x 10(-7) [mm(2)/s]/[nuclei/mm(2)]. The 95% CI for white matter = 0.25 x 10(-3) mm(2)/s, gray matter = 0.31 x 10(-3) mm(2)/s, a mixture of white and gray matter = 0.40 x 10(-3) mm(2)/s, and a mixture of white matter, gray matter, and cerebrospinal fluid = 0.75 x 10(-3) mm(2)/s. Application of these measurements as ADC thresholds produce varying levels of sensitivity and specificity to disease progression, which were all significantly better than chance.
  
  
  CONCLUSIONS
  This study suggests fDMs are valid biomarkers for brain tumor cellularity.
authors.affiliation: Translational Brain Tumor Program, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Ellingson
authors.forename: Mark G
authors.initials: MG
authors.lastname: Malkin
authors.forename: Scott D
authors.initials: SD
authors.lastname: Rand
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Connelly
authors.forename: Carolyn
authors.initials: C
authors.lastname: Quinsey
authors.forename: Pete S
authors.initials: PS
authors.lastname: LaViolette
authors.forename: Devyani P
authors.initials: DP
authors.lastname: Bedekar
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Schmainda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D001932:Brain Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D003198:Computer Simulation; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D005910:Glioma / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity