title: A Multiparametric Model for Mapping Cellularity in Glioblastoma Using Radiographically Localized Biopsies.
abstract: OBJECTIVE
  The complex MR imaging appearance of glioblastoma is a function of underlying histopathologic heterogeneity. A better understanding of these correlations, particularly the influence of infiltrating glioma cells and vasogenic edema on T2 and diffusivity signal in nonenhancing areas, has important implications in the management of these patients. With localized biopsies, the objective of this study was to generate a model capable of predicting cellularity at each voxel within an entire tumor volume as a function of signal intensity, thus providing a means of quantifying tumor infiltration into surrounding brain tissue.
  
  
  METHODS
  Ninety-one localized biopsies were obtained from 36 patients with glioblastoma. Signal intensities corresponding to these samples were derived from T1-postcontrast subtraction, T2-FLAIR, and ADC sequences by using an automated coregistration algorithm. Cell density was calculated for each specimen by using an automated cell-counting algorithm. Signal intensity was plotted against cell density for each MR image.
  
  
  RESULTS
  T2-FLAIR (r= -0.61) and ADC (r= -0.63) sequences were inversely correlated with cell density. T1-postcontrast (r= 0.69) subtraction was directly correlated with cell density. Combining these relationships yielded a multiparametric model with improved correlation (r= 0.74), suggesting that each sequence offers different and complementary information.
  
  
  CONCLUSIONS
  Using localized biopsies, we have generated a model that illustrates a quantitative and significant relationship between MR signal and cell density. Projecting this relationship over the entire tumor volume allows mapping of the intratumoral heterogeneity in both the contrast-enhancing tumor core and nonenhancing margins of glioblastoma and may be used to guide extended surgical resection, localized biopsies, and radiation field mapping.
authors.affiliation: From the Departments of Radiology (P.D.C., L.H.S., A.L., J.G.).
authors.forename: P D
authors.identifier: http://orcid.org/0000-0002-2675-9483
authors.initials: PD
authors.lastname: Chang
authors.affiliation: Neurological Surgery (H.R.M., S.G.B., B.J.A.G., T.H.U., Z.K.E., A.M.S., S.A.S., G.M.M., M.B.S., J.N.B.).|Gabriele Bartoli Brain Tumor Laboratory and the Irving Cancer Research Center (H.R.M., S.G.B., B.J.A.G., T.H.U., J.S., Z.K.E., A.M.S., J.N.B., P.C.), New York, New York.
authors.forename: H R
authors.identifier: http://orcid.org/0000-0002-4180-7017
authors.initials: HR
authors.lastname: Malone
authors.affiliation: Neurological Surgery (H.R.M., S.G.B., B.J.A.G., T.H.U., Z.K.E., A.M.S., S.A.S., G.M.M., M.B.S., J.N.B.).|Gabriele Bartoli Brain Tumor Laboratory and the Irving Cancer Research Center (H.R.M., S.G.B., B.J.A.G., T.H.U., J.S., Z.K.E., A.M.S., J.N.B., P.C.), New York, New York.
authors.forename: S G
authors.identifier: http://orcid.org/0000-0001-6320-210X
authors.initials: SG
authors.lastname: Bowden
authors.affiliation: Department of Radiology (D.S.C.), University of San Francisco School of Medicine, San Francisco, California.
authors.forename: D S
authors.identifier: http://orcid.org/0000-0002-2359-7394
authors.initials: DS
authors.lastname: Chow
authors.affiliation: Neurological Surgery (H.R.M., S.G.B., B.J.A.G., T.H.U., Z.K.E., A.M.S., S.A.S., G.M.M., M.B.S., J.N.B.).|Gabriele Bartoli Brain Tumor Laboratory and the Irving Cancer Research Center (H.R.M., S.G.B., B.J.A.G., T.H.U., J.S., Z.K.E., A.M.S., J.N.B., P.C.), New York, New York.
authors.forename: B J A
authors.identifier: http://orcid.org/0000-0001-5584-6714
authors.initials: BJA
authors.lastname: Gill
authors.affiliation: Neurological Surgery (H.R.M., S.G.B., B.J.A.G., T.H.U., Z.K.E., A.M.S., S.A.S., G.M.M., M.B.S., J.N.B.).|Gabriele Bartoli Brain Tumor Laboratory and the Irving Cancer Research Center (H.R.M., S.G.B., B.J.A.G., T.H.U., J.S., Z.K.E., A.M.S., J.N.B., P.C.), New York, New York.
authors.forename: T H
authors.identifier: http://orcid.org/0000-0003-4243-5208
authors.initials: TH
authors.lastname: Ung
authors.affiliation: Gabriele Bartoli Brain Tumor Laboratory and the Irving Cancer Research Center (H.R.M., S.G.B., B.J.A.G., T.H.U., J.S., Z.K.E., A.M.S., J.N.B., P.C.), New York, New York.
authors.forename: J
authors.identifier: http://orcid.org/0000-0003-2436-7539
authors.initials: J
authors.lastname: Samanamud
authors.affiliation: Neurological Surgery (H.R.M., S.G.B., B.J.A.G., T.H.U., Z.K.E., A.M.S., S.A.S., G.M.M., M.B.S., J.N.B.).|Gabriele Bartoli Brain Tumor Laboratory and the Irving Cancer Research Center (H.R.M., S.G.B., B.J.A.G., T.H.U., J.S., Z.K.E., A.M.S., J.N.B., P.C.), New York, New York.
authors.forename: Z K
authors.identifier: http://orcid.org/0000-0001-8544-7490
authors.initials: ZK
authors.lastname: Englander
authors.affiliation: Neurological Surgery (H.R.M., S.G.B., B.J.A.G., T.H.U., Z.K.E., A.M.S., S.A.S., G.M.M., M.B.S., J.N.B.).|Gabriele Bartoli Brain Tumor Laboratory and the Irving Cancer Research Center (H.R.M., S.G.B., B.J.A.G., T.H.U., J.S., Z.K.E., A.M.S., J.N.B., P.C.), New York, New York.
authors.forename: A M
authors.identifier: http://orcid.org/0000-0002-0241-7120
authors.initials: AM
authors.lastname: Sonabend
authors.affiliation: Neurological Surgery (H.R.M., S.G.B., B.J.A.G., T.H.U., Z.K.E., A.M.S., S.A.S., G.M.M., M.B.S., J.N.B.).
authors.forename: S A
authors.identifier: http://orcid.org/0000-0001-8770-8965
authors.initials: SA
authors.lastname: Sheth
authors.affiliation: Neurological Surgery (H.R.M., S.G.B., B.J.A.G., T.H.U., Z.K.E., A.M.S., S.A.S., G.M.M., M.B.S., J.N.B.).
authors.forename: G M
authors.identifier: http://orcid.org/0000-0002-9695-3564
authors.initials: GM
authors.lastname: McKhann
authors.affiliation: Neurological Surgery (H.R.M., S.G.B., B.J.A.G., T.H.U., Z.K.E., A.M.S., S.A.S., G.M.M., M.B.S., J.N.B.).
authors.forename: M B
authors.identifier: http://orcid.org/0000-0002-3222-985X
authors.initials: MB
authors.lastname: Sisti
authors.affiliation: From the Departments of Radiology (P.D.C., L.H.S., A.L., J.G.).
authors.forename: L H
authors.identifier: http://orcid.org/0000-0002-4379-6729
authors.initials: LH
authors.lastname: Schwartz
authors.affiliation: From the Departments of Radiology (P.D.C., L.H.S., A.L., J.G.).
authors.forename: A
authors.identifier: http://orcid.org/0000-0003-2908-9179
authors.initials: A
authors.lastname: Lignelli
authors.affiliation: From the Departments of Radiology (P.D.C., L.H.S., A.L., J.G.).
authors.forename: J
authors.identifier: http://orcid.org/0000-0001-7658-6755
authors.initials: J
authors.lastname: Grinband
authors.affiliation: Neurological Surgery (H.R.M., S.G.B., B.J.A.G., T.H.U., Z.K.E., A.M.S., S.A.S., G.M.M., M.B.S., J.N.B.) pc561@cumc.columbia.edu jnb2@cumc.columbia.edu.|Gabriele Bartoli Brain Tumor Laboratory and the Irving Cancer Research Center (H.R.M., S.G.B., B.J.A.G., T.H.U., J.S., Z.K.E., A.M.S., J.N.B., P.C.), New York, New York.
authors.forename: J N
authors.identifier: http://orcid.org/0000-0002-6844-0286
authors.initials: JN
authors.lastname: Bruce
authors.affiliation: Pathology and Cell Biology (P.C.), College of Physicians and Surgeons at Columbia University, New York, New York pc561@cumc.columbia.edu jnb2@cumc.columbia.edu.|Gabriele Bartoli Brain Tumor Laboratory and the Irving Cancer Research Center (H.R.M., S.G.B., B.J.A.G., T.H.U., J.S., Z.K.E., A.M.S., J.N.B., P.C.), New York, New York.
authors.forename: P
authors.identifier: http://orcid.org/0000-0002-7001-0226
authors.initials: P
authors.lastname: Canoll
mesh_terms: D000328:Adult; D000465:Algorithms; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D002452:Cell Count; D005260:Female; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D047368:Tumor Burden