Ultrasound in Medicine and Biology
Volume 33, Issue 2 , Pages 235-245, February 2007

Quantitative contrast enhanced ultrasound and ct assessment of tumor response to antiangiogenic therapy in rats

  • Rachel E. Pollard

      Affiliations

    • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis CA, USA
    • Corresponding Author InformationAddress correspondence to: Rachel E. Pollard, DVM, PhD, Department of Surgical and Radiological Sciences, University of California, Davis, School of Veterinary Medicine, Davis, CA 95616 USA.
    • ,
  • Amy R. Broumas

      Affiliations

    • Department of Biomedical Engineering, University of California, Davis, CA, USA
    • ,
  • Erik R. Wisner

      Affiliations

    • Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis CA, USA
    • ,
  • Sylvia V. Vekich

      Affiliations

    • Pfizer Global Research and Development, La Jolla, CA, USA
    • ,
  • Katherine W. Ferrara

      Affiliations

    • Department of Biomedical Engineering, University of California, Davis, CA, USA

Received 2 May 2006; received in revised form 17 July 2006; accepted 27 July 2006. published online 16 December 2006.

Abstract 

Contrast-enhanced computed tomography (CECT) and contrast-enhanced destruction-replenishment subharmonic ultrasound (CEDRSU) were used to quantify blood flow and tumor viability during antiangiogenic therapy. SU11657 or placebo was administered to R3230AC tumor-baring rats over a two-week period. CEDRSU vascular volume (ASI) and volume flow (VF) and CECT perfusion (PR) and permeability (PM) measurements were made on day 0, 7 and 14. The percent change in imaging parameters was calculated between day 0 and 7 and 14. Serum drug level (SDL) was compared with imaging parameters. Imaging estimates of tumor viability were compared with histology images on day 14. The percent change in imaging measures for control and treated groups were significantly different on day 7(ASI, p = 0.02; VF, p = 0.008, PR, p = 0.0007; PM, p = 0.003) and 14 (ASI, p = 0.0004; VF, p = 0.002, PR, p = 0.003; PM, p = 0.005). Imaging identified animals with lower SDLs as having higher tumor vascularity and flow. Spatial estimates of tumor viability correlated with histology (CEDRSU, r2 = 0.92, p ≪ 0.001; CT, r2 = 0.86, p ≪ 0.001). CEDRSU and CECT provide measures of blood flow and viability in tumors during antiangiogenic therapy. Tumors with higher flow were identified in animals with lower SDL. SU11657 treatment results in decreased tumor flow and viability. (E-mail: repollard@ucdavis.edu)

Key Words: Contrast ultrasound, Contrast CT, Antiangiogenic therapy, Quantitative imaging

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PII: S0301-5629(06)01778-9

doi:10.1016/j.ultrasmedbio.2006.07.036

Ultrasound in Medicine and Biology
Volume 33, Issue 2 , Pages 235-245, February 2007

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