Ultrasound imaging of angiogenesis

Among the early changes that differentiate normal from cancerous tissues is the process by which the tumor develops its blood supply, tumor angiogenesis. The development of anti-angiogenesis agents and the clinical evaluation of such therapy have stimulated interest in non-invasive imaging methods to monitor response. Ultrasound has great potential in providing clinically relevant information related to angiogenesis by measuring tumor flow and vascular volume. In this presentation the fundamentals of angiogenesis and the implications for ultrasound imaging is described with an emphasis on the use of ultrasound contrast agents. We show that power Doppler and pulse inversion harmonic imaging correlates with Cyclooxygenase-2 (COX-2), an immunohistochemical predictor of angiogenesis, in a murine melanoma xenograft model (p<0.05). Preliminary results from a human trial of Angiostatin (Entremed, Rockville, NID) are also presented. In conclusion, contrast enhanced ultrasound imaging of tumor neovascularity may provide noninvasive markers of angiogenesis.