title: Cluster analysis of quantitative parametric maps from DCE-MRI: application in evaluating heterogeneity of tumor response to antiangiogenic treatment.
abstract: OBJECTIVE
  The objective of this study was to compare a clustering approach to conventional analysis methods for assessing changes in pharmacokinetic parameters obtained from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) during antiangiogenic treatment in a breast cancer model.
  
  
  METHODS
  BALB/c mice bearing established transplantable her2+ tumors were treated with a DNA-based antiangiogenic vaccine or with an empty plasmid (untreated group). DCE-MRI was carried out by administering a dose of 0.05 mmol/kg of Gadocoletic acid trisodium salt, a Gd-based blood pool contrast agent (CA) at 1T. Changes in pharmacokinetic estimates (K(trans) and vp) in a nine-day interval were compared between treated and untreated groups on a voxel-by-voxel analysis. The tumor response to therapy was assessed by a clustering approach and compared with conventional summary statistics, with sub-regions analysis and with histogram analysis.
  
  
  RESULTS
  Both the K(trans) and vp estimates, following blood-pool CA injection, showed marked and spatial heterogeneous changes with antiangiogenic treatment. Averaged values for the whole tumor region, as well as from the rim/core sub-regions analysis were unable to assess the antiangiogenic response. Histogram analysis resulted in significant changes only in the vp estimates (p<0.05). The proposed clustering approach depicted marked changes in both the K(trans) and vp estimates, with significant spatial heterogeneity in vp maps in response to treatment (p<0.05), provided that DCE-MRI data are properly clustered in three or four sub-regions.
  
  
  CONCLUSIONS
  This study demonstrated the value of cluster analysis applied to pharmacokinetic DCE-MRI parametric maps for assessing tumor response to antiangiogenic therapy.
authors.affiliation: Institute of Biostructure and Bioimaging (CNR) c/o Molecular Biotechnologies Center, Via Nizza 52, 10126, Torino, Italy; Molecular Imaging Center, University of Torino, Via Nizza 52, 10126 Torino, Italy.
authors.forename: Dario Livio
authors.initials: DL
authors.lastname: Longo
authors.affiliation: Molecular Imaging Center, University of Torino, Via Nizza 52, 10126 Torino, Italy; Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126 Torino, Italy.
authors.forename: Walter
authors.initials: W
authors.lastname: Dastrù
authors.affiliation: Molecular Imaging Center, University of Torino, Via Nizza 52, 10126 Torino, Italy; Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126 Torino, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Consolino
authors.affiliation: Dept. of Computer Science, University College London, Gower Street, London WC1E 6BT, United Kingdom.
authors.forename: Miklos
authors.initials: M
authors.lastname: Espak
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126 Torino, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Arigoni
authors.affiliation: Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126 Torino, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Cavallo
authors.affiliation: Molecular Imaging Center, University of Torino, Via Nizza 52, 10126 Torino, Italy; Department of Molecular Biotechnology and Health Sciences, University of Torino, Via Nizza 52, 10126 Torino, Italy. Electronic address: silvio.aime@unito.it.
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy*; D016000:Cluster Analysis; D003287:Contrast Media / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D005682:Gadolinium / Q000493:pharmacokinetics; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D005682:Gadolinium
keywords: Antiangiogenic; Clustering; DCE-MRI; Gd-complexes; Pharmacokinetic modeling; Tumor heterogeneity