title: Quantitative assessment of tumor angiogenesis using real-time motion-compensated contrast-enhanced ultrasound imaging.
abstract: OBJECTIVE
  To develop and test a real-time motion compensation algorithm for contrast-enhanced ultrasound imaging of tumor angiogenesis on a clinical ultrasound system.
  
  
  METHODS
  The Administrative Institutional Panel on Laboratory Animal Care approved all experiments. A new motion correction algorithm measuring the sum of absolute differences in pixel displacements within a designated tracking box was implemented in a clinical ultrasound machine. In vivo angiogenesis measurements (expressed as percent contrast area) with and without motion compensated maximum intensity persistence (MIP) ultrasound imaging were analyzed in human colon cancer xenografts (n = 64) in mice. Differences in MIP ultrasound imaging signal with and without motion compensation were compared and correlated with displacements in x- and y-directions. The algorithm was tested in an additional twelve colon cancer xenograft-bearing mice with (n = 6) and without (n = 6) anti-vascular therapy (ASA-404). In vivo MIP percent contrast area measurements were quantitatively correlated with ex vivo microvessel density (MVD) analysis.
  
  
  RESULTS
  MIP percent contrast area was significantly different (P < 0.001) with and without motion compensation. Differences in percent contrast area correlated significantly (P < 0.001) with x- and y-displacements. MIP percent contrast area measurements were more reproducible with motion compensation (ICC = 0.69) than without (ICC = 0.51) on two consecutive ultrasound scans. Following anti-vascular therapy, motion-compensated MIP percent contrast area significantly (P = 0.03) decreased by 39.4 ± 14.6 % compared to non-treated mice and correlated well with ex vivo MVD analysis (Rho = 0.70; P = 0.05).
  
  
  CONCLUSIONS
  Real-time motion-compensated MIP ultrasound imaging allows reliable and accurate quantification and monitoring of angiogenesis in tumors exposed to breathing-induced motion artifacts.
authors.affiliation: Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, 300 Pasteur Drive, Room H1307, Stanford, CA, USA.
authors.forename: Marybeth A
authors.initials: MA
authors.lastname: Pysz
authors.forename: Ismayil
authors.initials: I
authors.lastname: Guracar
authors.forename: Kira
authors.initials: K
authors.lastname: Foygel
authors.forename: Lu
authors.initials: L
authors.lastname: Tian
authors.forename: Jürgen K
authors.initials: JK
authors.lastname: Willmann
mesh_terms: D000465:Algorithms; D000818:Animals; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D014183:Transplantation, Heterologous; D014465:Ultrasonics; D014463:Ultrasonography