Mouse studies offer tremendous insight into the development of normal tissues and of diseased tissues including cancer. The ability to image mice repeatedly and non-invasively is necessary for understanding the course of therapeutic interventions and to minimize the use of mice in experimentation. Ultrasound imaging is the accepted standard for high resolution imaging, offering the ability for repeated, inexpensive, investigator-operated, real-time monitoring of mice. The many NIH-funded investigators using mice at the University of California San Francisco Parnassus have relied on a Vevo 770 ultrasound small animal imager that will be moved to the newly opened research campus at Mission Bay. This planned move will leave the investigators without the ability for noninvasive imaging. Because the mice are behind a barrier, longitudinal studies by other imaging modalities such as MRI, CT or PET scanning are not possible due to their locations outside the barrier facility. Thus, these investigators have joined to apply for a new ultrasound and, in the process, have decided to take advantage of the higher resolution, greater depth of field and capabilities for vascular analysis of the new Vevo 2100. The multiple major users on this application are diverse, but are united by the desire to carry out longitudinal, non-invasive studies in mice. The high resolution imaging will enhance the ability of researchers to diagnose tumor development de novo, localize tissues for accurate injection, and confirm early implantation and monitor embryonic development in models of lung development. The increased depth of focus will enable visualization of organs throughout the abdomen, needed for detecting and monitoring pancreatic tumors and mesothelioma. The Doppler components (pulsed wave and power) will permit visualization of the vasculature of a tissue and its change over time. The 3D capability will rapidly and accurately measure the volume of a defined structure, such as a tumor, and will display the heterogeneity of tissues so that different regions can be analyzed separately. Finally, the contrast enhancement features expand the capabilities of the ultrasound: with non-targeted synthetic bubbles, the Vevo 2100 can quantify relative blood flow to an organ;with synthetic bubbles targeted to various endothelial targets such as VEGF receptor, the Vevo 2100 can identify relative expression of the targets characteristic of tumor angiogenesis. A Vevo 2100 Small Animal Imager would immediately address the needs of the NIH- funded investigators included here as major users and would enhance opportunities for all mouse users of the barrier facility. With the added support of the Simmons Mesothelioma Foundation to provide long-term maintenance, this state-of-the-art small animal imager will enhance research for the diverse community of those studying mice at UCSF. Relevance to Public Health: Mouse models of human disease are essential for understanding the underlying biology of disease and for developing effective therapies. The translational value of studies will be greatly enhanced by the ability to image living mice non-invasively and repetitively over time. A small animal ultrasound imaging system will allow investigators to monitor mice used in their research for the development of conditions and the response to therapy, thereby increasing efficiency, reducing the number of mice needed, and speeding the development of potential treatments for patients.
