title: Precise ex vivo histological validation of heightened cellularity and diffusion-restricted necrosis in regions of dark apparent diffusion coefficient in 7 cases of high-grade glioma.
abstract: BACKGROUND
  Recent conflicting reports have found both brain tumor hypercellularity and necrosis in regions of restricted diffusion on MRI-derived apparent diffusion coefficient (ADC) images. This study precisely compares ADC and cell density voxel by voxel using postmortem human whole brain samples.
  
  
  METHODS
  Patients with meningioma were evaluated to determine a normative ADC distribution within benign fluid attenuated inversion recovery (FLAIR) T2/hyperintensity surrounding tumor. This distribution was used to calculate a minimum ADC threshold to define regions of ADC-FLAIR mismatch (AFMM), where restricted diffusion presented in conjunction with T2/FLAIR hyperintensity. Contrast-enhancing voxels were excluded from this analysis. AFMM maps were generated using imaging acquired prior to death in 7 patients with high-grade glioma who eventually donated their brains upon death. Histological samples were taken from numerous regions of abnormal FLAIR and AFMM. Each sample was computationally processed to determine cell density. Custom software was then used to downsample coregistered microscopic histology to the more coarse MRI resolution. A voxel-by-voxel evaluation comparing ADC and cellularity was then performed.
  
  
  RESULTS
  An ADC threshold of 0.929 × 10(-3) mm(2)/s was calculated from meningioma-induced edema and was used to define AFMM. Regions of AFMM showed significantly greater cell density in 6 of 7 high-grade glioma cases compared with regions of hyperintense FLAIR alone (P < .0001). Two patients had small regions of diffusion-restricted necrosis that had significantly lower ADC than nearby hypercellularity.
  
  
  CONCLUSIONS
  Regions of AFMM contain hypercellularity except for regions with extremely restricted diffusion, where necrosis is present.
authors: Department of Radiology (P.S.L., S.D.R., K.M.S.), Department of Biophysics (N.J.M., K.M.S.), Department of Pathology (E.J.C.), Department of Neurology (J.C., M.G.M.), Department of Radiation Oncology (J.A.B.), and Department of Neurosurgery (M.G.M., W.M.M.), Medical College of Wisconsin, Milwaukee, Wisconsin.
authors: Peter S
authors: PS
authors: LaViolette
authors: Department of Radiology (P.S.L., S.D.R., K.M.S.), Department of Biophysics (N.J.M., K.M.S.), Department of Pathology (E.J.C.), Department of Neurology (J.C., M.G.M.), Department of Radiation Oncology (J.A.B.), and Department of Neurosurgery (M.G.M., W.M.M.), Medical College of Wisconsin, Milwaukee, Wisconsin.
authors: Nikolai J
authors: NJ
authors: Mickevicius
authors: Department of Radiology (P.S.L., S.D.R., K.M.S.), Department of Biophysics (N.J.M., K.M.S.), Department of Pathology (E.J.C.), Department of Neurology (J.C., M.G.M.), Department of Radiation Oncology (J.A.B.), and Department of Neurosurgery (M.G.M., W.M.M.), Medical College of Wisconsin, Milwaukee, Wisconsin.
authors: Elizabeth J
authors: EJ
authors: Cochran
authors: Department of Radiology (P.S.L., S.D.R., K.M.S.), Department of Biophysics (N.J.M., K.M.S.), Department of Pathology (E.J.C.), Department of Neurology (J.C., M.G.M.), Department of Radiation Oncology (J.A.B.), and Department of Neurosurgery (M.G.M., W.M.M.), Medical College of Wisconsin, Milwaukee, Wisconsin.
authors: Scott D
authors: SD
authors: Rand
authors: Department of Radiology (P.S.L., S.D.R., K.M.S.), Department of Biophysics (N.J.M., K.M.S.), Department of Pathology (E.J.C.), Department of Neurology (J.C., M.G.M.), Department of Radiation Oncology (J.A.B.), and Department of Neurosurgery (M.G.M., W.M.M.), Medical College of Wisconsin, Milwaukee, Wisconsin.
authors: Jennifer
authors: J
authors: Connelly
authors: Department of Radiology (P.S.L., S.D.R., K.M.S.), Department of Biophysics (N.J.M., K.M.S.), Department of Pathology (E.J.C.), Department of Neurology (J.C., M.G.M.), Department of Radiation Oncology (J.A.B.), and Department of Neurosurgery (M.G.M., W.M.M.), Medical College of Wisconsin, Milwaukee, Wisconsin.
authors: Joseph A
authors: JA
authors: Bovi
authors: Department of Radiology (P.S.L., S.D.R., K.M.S.), Department of Biophysics (N.J.M., K.M.S.), Department of Pathology (E.J.C.), Department of Neurology (J.C., M.G.M.), Department of Radiation Oncology (J.A.B.), and Department of Neurosurgery (M.G.M., W.M.M.), Medical College of Wisconsin, Milwaukee, Wisconsin.
authors: Mark G
authors: MG
authors: Malkin
authors: Department of Radiology (P.S.L., S.D.R., K.M.S.), Department of Biophysics (N.J.M., K.M.S.), Department of Pathology (E.J.C.), Department of Neurology (J.C., M.G.M.), Department of Radiation Oncology (J.A.B.), and Department of Neurosurgery (M.G.M., W.M.M.), Medical College of Wisconsin, Milwaukee, Wisconsin.
authors: Wade M
authors: WM
authors: Mueller
authors: Department of Radiology (P.S.L., S.D.R., K.M.S.), Department of Biophysics (N.J.M., K.M.S.), Department of Pathology (E.J.C.), Department of Neurology (J.C., M.G.M.), Department of Radiation Oncology (J.A.B.), and Department of Neurosurgery (M.G.M., W.M.M.), Medical College of Wisconsin, Milwaukee, Wisconsin.
authors: Kathleen M
authors: KM
authors: Schmainda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001929:Brain Edema / Q000473:pathology; D004058:Diffusion; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D005260:Female; D005910:Glioma / Q000473:pathology*; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000473:pathology*; D008579:Meningioma / Q000473:pathology*; D008875:Middle Aged; D009336:Necrosis
keywords: ADC; FLAIR; brain tumor; diffusion; glioblastoma