Imaging Cancer Angiogenesis with Acoustic Angiography Ultrasound

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ABSTRACT Early detection is a critical component of the fight against cancer, and it results in better chances of survival than when tumors are diagnosed at advanced stages. However, as physicians aim to detect increasingly smaller tumors, the resolution and sensitivity of modern imaging modalities become problematic. Therefore, in this project, I hypothesize that tumors can be detected by visualizing the structure of the underlying blood vessels using a novel ultrasound technique called acoustic angiography which was developed in Dr. Paul Dayton’s laboratory. Angiogenesis, the growth of new blood vessels from existing ones, is stimulated by growing tumors as they require new vasculature to supply their rapid growth. However, the new vessels that form do not become mature, healthy vasculature. Instead, tumor vessels are leaky, disorganized, and often shaped into bent and twisted forms. Acoustic angiography allows us to use microbubble contrast agents and novel ultrasound technology to visualize vasculature at least 100 μm in diameter and assess the degree of tortuosity of individual blood vessels. In this project, I will characterize the tortuosity of developing tumors in a model of triple-negative breast cancer and compare it to that of normal blood vessels. Tumors are expected to have higher vascular density and tortuosity than healthy tissue because of the rampant, abnormal angiogenesis induced by tumor growth. Additionally, I will evaluate the minimum limit of tumor detection based on acoustic angiography images using a radiology reader study and a quantitative tumor detection model to evaluate the accuracy of image classification (as tumor or healthy) for tumors of different sizes. We will also determine if the distribution of molecular markers of angiogenesis is correlated to visible tortuosity using molecular acoustic angiography. Finally, we will evaluate the clinical feasibility of using acoustic angiography for imaging suspicious breast lesions by imaging patients with BI-RADS 4 and 5 lesions prior to biopsy and performing a reader study to determine if acoustic angiography has superior diagnostic utility than traditional ultrasound, with the goal of eventually avoiding unnecessary biopsies. The final results of my dissertation research will determine whether vascular tortuosity revealed by acoustic angiography ultrasound images can be used to detect tumors, and will establish the minimum detectable tumor size. Furthermore, it will also correlate molecular imaging of angiogenesis to vascular tortuosity. Future research directions include deepening my understanding of the cellular and molecular mechanisms of angiogenesis and training in a complementary imaging modality.