Determination of breast cancer response to bevacizumab therapy using contrast-enhanced ultrasound and artificial neural networks

Kenneth Hoyt, Jason M. Warram, Heidi Umphrey, Lin Belt, Mark E. Lockhart, Michelle L. Robbin, Kurt R. Zinn

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Objective. The purpose of this study was to evaluate contrast-enhanced ultrasound and neural network data classification for determining the breast cancer response to bevacizumab therapy in a murine model. Methods. An ultrasound scanner operating in the harmonic mode was used to measure ultrasound contrast agent (UCA) time-intensity curves in vivo. Twenty-five nude athymic mice with orthotopic breast cancers received a 30-μL tail vein bolus of a perflutren microsphere UCA, and baseline tumor imaging was performed using microbubble destruction-replenishment techniques. Subsequently, 15 animals received a 0.2-mg injection of bevacizumab, whereas 10 control animals received an equivalent dose of saline. Animals were reimaged on days 1, 2, 3, and 6 before euthanasia. Histologic assessment of excised tumor sections was performed. Time-intensity curve analysis for a given region of interest was conducted using customized software. Tumor perfusion metrics on days 1, 2, 3, and 6 were modeled using neural network data classification schemes (60% learning and 40% testing) to predict the breast cancer response to therapy. Results. The breast cancer response to a single dose of bevacizumab in a murine model was immediate and transient. Permutations of input to the neural network data classification scheme revealed that tumor perfusion data within 3 days of bevacizumab dosing was sufficient to minimize the prediction error to 10%, whereas measurements of physical tumor size alone did not appear adequate to assess the therapeutic response. Conclusions. Contrast-enhanced ultrasound may be a useful tool for determining the response to bevacizumab therapy and monitoring the subsequent restoration of blood flow to breast cancer.

Original languageEnglish (US)
Pages (from-to)577-585
Number of pages9
JournalJournal of Ultrasound in Medicine
Issue number4
StatePublished - Apr 1 2010


  • Bevacizumab
  • Breast cancer
  • Contrast agent
  • Neural networks
  • Ultrasound

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging


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