Acoustic Angiography: A New Imaging Platform for High Resolution Mapping of Microvasculature and Tumor Assessment

Abstract

Statistically, one in four Americans will die from cancer. Many new tumor detection and therapeutic approaches have improved patient outcomes, but cancer continues to run rampant in our country; it claimed the lives of 1.6 million Americans in 2012. To put this number of annual deaths in perspective, it is over 500 times the number of people who died in the horrific attacks on September 11, 2001. This dissertation does not offer either an antidote to the disease, nor a detection mechanism appropriate for all tumor types. It does, however, present the description and characterization of a novel dual-frequency ultrasound imaging transducer, capable of operating in a new imaging mode we call `acoustic angiography.' These images offer high resolution and high contrast 3D depictions of the microvasculature; herein we demonstrate its cancer assessment utility by way of multiple imaging studies. Throughout this dissertation, image data from both healthy and diseased tissues are presented. Additionally, acoustic assessments of vasculature within an ex vivo biomatrix scaffold model (a platform for creating of artificial organs) are presented. A vessel mapping algorithm, originally developed for human magnetic resonance angiography images, has been implemented in both in vivo and ex vivo tissue volumes. A novel microvessel phantom generation technique is presented, which allows ground-truth coordinates for vascular networks to be defined and imaged. Finally, the ultrasound pulsing technique, radiation force, was used as a method to improve the diagnostic sensitivity of ultrasound to malignant tumors. Together, the results of these studies suggest that the imaging approach, acoustic angiography, enabled by our new dual-frequency ultrasound transducer, could eventually be used to detect and monitor tumors in a clinical imaging context. This dissertation supports the following three hypotheses: 1) A prototype dual-frequency ultrasound transducer can be used to depict in vivo microvasculature, 2) These microvascular images can be quantitatively assessed as a means to characterize the presence of a tumor, and evaluate tumor response to therapy, and 3) Radiation force can be used as a method to improve ultrasonic diagnostic sensitivity to the presence of a tumor.Doctor of Philosoph

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