High resolution ultrasonic vessel imaging and repeatability of blood flow modeling using an ultrasound contrast agent

Abstract

Cancer is a complex and adaptable disease, and knowledge of the mechanisms that cause its progression is vital to creating and monitoring anti-cancer therapies. As a tumor grows beyond a few mm3, blood vessels are recruited to provide additional nutrients in a process called angiogenesis. Some novel drug therapies specifically target this process, and the efficacy of these drugs can in principle be monitored by a technique called angiography. 3D angiography, a method of imaging the vasculature, can be performed by several imaging modalities typically with the use of a contrast agent. A technique is introduced which uses high resolution ultrasound in conjunction with an ultrasound contrast agent to produce 3D images of the vasculature. This method offers a faster, more accessible, and cheaper alternative to assess the efficacy of anti-angiogenic drugs in preclinical cancer models. In addition to vessel imaging, modeling the kinetic behavior of the contrast agent in the vasculature can elucidate parameters such as blood flow, which can also serve as an indicator of drug treatment efficacy. The repeatability of a commonly used mono-exponential model is assessed in order to determine thresholds for inter/intra-subject error. The 3D vessel imaging technique presented in this thesis correlated with other measures of blood flow (r = 0.55 ± 0.04, p < 0.01) and shows an increased sensitivity to microvasculature within tumors. Also, preliminary repeatability analysis (n = 6) on the modeling parameter which is proportional to contrast agent velocity shows a mean difference of 0.061 ± 0.298 between independent measurements, and the limits of agreement range from -0.536 and 0.656. The developments exhibited provide additional methods for monitoring longitudinal anti-angiogenic cancer treatments in preclinical models.