3-D microvessel-mimicking ultrasound phantoms produced with a scanning motion system

Ultrasound techniques are currently being developed that can assess the vascularization of tissue as a marker for therapeutic response. Some of these ultrasound imaging techniques seek to extract quantitative features about vessel networks, whereas high-frequency imaging also allows individual vessels to be resolved. The development of these new techniques, and subsequent imaging analysis strategies, necessitates an understanding of their sensitivities to vessel and vessel network structural abnormalities. Constructing in-vitro flow phantoms for this purpose can be prohibitively challenging, because simulating precise flow environments with nontrivial structures is often impossible using conventional methods of construction for flow phantoms. Presented in this manuscript is a method to create predefined structures with <10 microm precision using a three-axis motion system. The application of this technique is demonstrated for the creation of individual vessel and vessel networks, which can easily be made to simulate the development of structural abnormalities typical of diseased vasculature in vivo. In addition, beyond facilitating the creation of phantoms that would otherwise be very challenging to construct, the method presented herein enables one to precisely simulate very slow blood flow and respiration artifacts, and to measure imaging resolution.