title: Three-dimensional Dynamic Contrast-enhanced US Imaging for Early Antiangiogenic Treatment Assessment in a Mouse Colon Cancer Model.
abstract: OBJECTIVE
  To evaluate feasibility and reproducibility of three-dimensional (3D) dynamic contrast material-enhanced (DCE) ultrasonographic (US) imaging by using a clinical matrix array transducer to assess early antiangiogenic treatment effects in human colon cancer xenografts in mice.
  
  
  METHODS
  Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care at Stanford University. Three-dimensional DCE US imaging with two techniques (bolus and destruction-replenishment) was performed in human colon cancer xenografts (n = 38) by using a clinical US system and transducer. Twenty-one mice were imaged twice to assess reproducibility. Seventeen mice were scanned before and 24 hours after either antiangiogenic (n = 9) or saline-only (n = 8) treatment. Data sets of 3D DCE US examinations were retrospectively segmented into consecutive 1-mm imaging planes to simulate two-dimensional (2D) DCE US imaging. Six perfusion parameters (peak enhancement [PE], area under the time-intensity curve [AUC], time to peak [TTP], relative blood volume [rBV], relative blood flow [rBF], and blood flow velocity) were measured on both 3D and 2D data sets. Percent area of blood vessels was quantified ex vivo with immunofluorescence. Statistical analyses were performed with the Wilcoxon rank test by calculating intraclass correlation coefficients and by using Pearson correlation analysis.
  
  
  RESULTS
  Reproducibility of both 3D DCE US imaging techniques was good to excellent (intraclass correlation coefficient, 0.73-0.86). PE, AUC, rBV, and rBF significantly decreased (P ≤ .04) in antiangiogenic versus saline-treated tumors. rBV (r = 0.74; P = .06) and rBF (r = 0.85; P = .02) correlated with ex vivo percent area of blood vessels, although the statistical significance of rBV was not reached, likely because of small sample size. Overall, 2D DCE-US overestimated and underestimated treatment effects from up to 125-fold to170-fold compared with 3D DCE US imaging. If the central tumor plane was assessed, treatment response was underestimated up to threefold or overestimated up to 57-fold on 2D versus 3D DCE US images.
  
  
  CONCLUSIONS
  Three-dimensional DCE US imaging with a clinical matrix array transducer is feasible and reproducible to assess tumor perfusion in human colon cancer xenografts in mice and allows for assessment of early treatment response after antiangiogenic therapy.
authors.affiliation: From the Department of Radiology, Molecular Imaging Program at Stanford (H.W., J.Q., J.K.W.), Department of Radiation Oncology (D.H.), and Department of Health, Research & Policy (L.T.), Stanford University School of Medicine, 300 Pasteur Dr, Room H1307, Stanford, CA 94305-5621.
authors.forename: Huaijun
authors.initials: H
authors.lastname: Wang
authors.affiliation: From the Department of Radiology, Molecular Imaging Program at Stanford (H.W., J.Q., J.K.W.), Department of Radiation Oncology (D.H.), and Department of Health, Research & Policy (L.T.), Stanford University School of Medicine, 300 Pasteur Dr, Room H1307, Stanford, CA 94305-5621.
authors.forename: Dimitre
authors.initials: D
authors.lastname: Hristov
authors.affiliation: From the Department of Radiology, Molecular Imaging Program at Stanford (H.W., J.Q., J.K.W.), Department of Radiation Oncology (D.H.), and Department of Health, Research & Policy (L.T.), Stanford University School of Medicine, 300 Pasteur Dr, Room H1307, Stanford, CA 94305-5621.
authors.forename: Jiale
authors.initials: J
authors.lastname: Qin
authors.affiliation: From the Department of Radiology, Molecular Imaging Program at Stanford (H.W., J.Q., J.K.W.), Department of Radiation Oncology (D.H.), and Department of Health, Research & Policy (L.T.), Stanford University School of Medicine, 300 Pasteur Dr, Room H1307, Stanford, CA 94305-5621.
authors.forename: Lu
authors.initials: L
authors.lastname: Tian
authors.affiliation: From the Department of Radiology, Molecular Imaging Program at Stanford (H.W., J.Q., J.K.W.), Department of Radiation Oncology (D.H.), and Department of Health, Research & Policy (L.T.), Stanford University School of Medicine, 300 Pasteur Dr, Room H1307, Stanford, CA 94305-5621.
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Willmann
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000068258:Bevacizumab / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D003287:Contrast Media; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D051379:Mice; D008819:Mice, Nude; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014463:Ultrasonography
chemical_list: D020533:Angiogenesis Inhibitors; D003287:Contrast Media; D000068258:Bevacizumab