Contrast-Enhanced Ultrasound for the Assessment of Response to Therapy

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  • March 22, 2019
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  • Rojas, Juan
    • Affiliation: School of Medicine, UNC/NCSU Joint Department of Biomedical Engineering
Abstract
  • Accurate assessment of cancer response to therapy is important for effective treatment outcome and limiting unnecessary therapeutics. The clinical gold standard for evaluating response to therapy consists of tracking changes in volume, which works well for cytotoxic treatments such and radio or chemo therapies, which directly induce cancer cell death. However, tumor volume is ineffective for tracking response to treatments such as antiangiogenic therapies, which target the formation of new blood vessels, and often lags behind the real effect of the drugs. Studies have shown that techniques such as dynamic contrast-enhanced magnetic resonance imaging, computed tomography, and positron emission tomography perform better at predicting and assessing response to therapy than changes in volume. However, these imaging modalities are expensive, cumbersome, expose patients to ionizing radiation, and use contrast agents that can often be harmful to patients. Contrast-enhanced ultrasound (CEUS) is an imaging modality that is inexpensive, real-time, and uses microbubble contrast agents that are safe and can be used to obtain quantitative measurements of blood perfusion and levels of endothelial biomarker expression. Moreover, CEUS has been shown to assess response to therapy more accurately than tumor volume in rodent tumor models. The first hypothesis of this dissertation is that that CEUS can evaluate and track response to therapies more accurately than changes in tumor volume. The results show that CEUS can assess response to therapies that are disruptive to tumor vessel formation earlier than tumor volume. Specifically, the techniques discussed here include perfusion imaging, ultrasound molecular imaging of angiogenesis biomarkers, and acoustic angiography, which can provide metrics about microvessel morphology and density. The second hypothesis is that CEUS can be performed using phase-change contrast agents (PCCAs). PCCAs have better circulation times than conventional microbubbles and can be small enough to escape the vasculature for extravascular diagnostic imaging, and thus, may provide multiple advantages for the assessment of response to therapy. The development of techniques to perform perfusion and molecular imaging using PCCAs is described. The results show that PCCAs can be used for intravascular molecular imaging, but major modifications to the formulation are required to obtain meaningful measurements of perfusion.
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Advisor
  • Rathmell, W. Kimryn
  • Lee, Yueh
  • Dayton, Paul
  • Pinton, Gianmarco
  • Goldberg, Richard
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2018
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