title: Intratumor heterogeneity in blood perfusion in orthotopic human melanoma xenografts assessed by dynamic contrast-enhanced magnetic resonance imaging.
abstract: OBJECTIVE
  To determine the intratumor heterogeneity in blood perfusion of orthotopic human melanoma xenografts by use of gadopentetate dimeglumine (Gd-DTPA)-based dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).
  
  
  METHODS
  Orthotopic xenografts of an amelanotic human melanoma cell line (A-07) were scanned sagittally, coronally, and axially in three subsequent DCE-MRI sessions, using spoiled gradient recalled sequences, a voxel size of 0.31x0.62x2.0 mm3, and an interleaving acquisition method to avoid slice gaps. Tumor images of E . F (E is initial extraction fraction and F is perfusion) were produced by subjecting the DCE-MRI data to Kety analysis. E . F was used as a parameter for tumor blood perfusion, since E for Gd-DTPA is close to unity in A-07 tumors.
  
  
  RESULTS
  All A-07 tumors subjected to investigation showed anisotropic radial heterogeneity in blood perfusion. The blood perfusion was low in the center of the tumors and increased toward the tumor periphery in the cranial, dorsal, caudal, and ventral directions, but not in the lateral and medial directions. In addition, 9 of 10 tumors showed blood perfusion hot spots in central or nonperipheral regions. The hot spots differed significantly between tumors in size, shape, location, and intensity, and appeared to be governed by stochastic processes. This heterogeneity superimposed the radial heterogeneity, but did not overshadow it in any tumor.
  
  
  CONCLUSIONS
  Orthotopic human melanoma xenografts show significant intratumor heterogeneity in blood perfusion. This heterogeneity is made up of two distinctly different components, one stochastic and one nonstochastic radial component. The radial component is anisotropic and dominant and is superimposed by the stochastic component.
authors.affiliation: Group of Radiation Biology and Tumor Physiology, Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway.
authors.forename: Jon-Vidar
authors.initials: JV
authors.lastname: Gaustad
authors.forename: Ilana C
authors.initials: IC
authors.lastname: Benjaminsen
authors.forename: Bjørn A
authors.initials: BA
authors.lastname: Graff
authors.forename: Kjetil G
authors.initials: KG
authors.lastname: Brurberg
authors.forename: Else-Beate M
authors.initials: EB
authors.lastname: Ruud
authors.forename: Einar K
authors.initials: EK
authors.lastname: Rofstad
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008546:Melanoma, Experimental / Q000098:blood supply*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA