Quantitative assessment of tumor angiogenesis using real-time motion-compensated contrast-enhanced ultrasound imaging
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ORIGINAL PAPER
Quantitative assessment of tumor angiogenesis using real-time motion-compensated contrast-enhanced ultrasound imaging Marybeth A. Pysz • Ismayil Guracar • Kira Foygel • Lu Tian • Ju¨rgen K. Willmann
Received: 8 November 2011 / Accepted: 2 April 2012 / Published online: 26 April 2012 Ó Springer Science+Business Media B.V. 2012
Abstract Purpose To develop and test a real-time motion compensation algorithm for contrast-enhanced ultrasound imaging of tumor angiogenesis on a clinical ultrasound system. Materials and 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 (ASAElectronic supplementary material The online version of this article (doi:10.1007/s10456-012-9271-3) contains supplementary material, which is available to authorized users. M. A. Pysz K. Foygel J. K. Willmann (&) Molecular Imaging Program at Stanford, Department of Radiology, Stanford University School of Medicine, 300 Pasteur Drive, Room H1307, Stanford, CA, USA e-mail: [email protected] I. Guracar Siemens Healthcare, Ultrasound Business Unit, Mountain View, CA, USA L. Tian Department of Health, Research and Policy, Stanford University, Stanford, CA, USA
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 antivascular 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). Conclusion Real-time motion-compensated MIP ultrasound imaging allows reliable and accurate quantification and monitoring of angiogenesis in tumors exposed to breathing-induced motion artifacts. Keywords Maximum intensity persistence MIP Cancer Ultrasound Microbubbles Vascular disrupting agent VDA
Introduction Contrast-enhanced ultrasound imaging with contrast microbubbles (gas-filled, lipid-shelled micr
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