We propose to purchase a commercial small animal ultrasound (US) imaging system, specifically, the VisualSonics Vevo 770(R) high-resolution in vivo imaging system. It will primarily serve five NIH-funded research teams to undertake biomedical research. In addition, through a Small Animal Imaging Research Program (U24- SAIRP) it will support 10 other current research investigations and serve as a catalyst for new research. It is widely recognized that imaging enhances biomedical research, particularly in oncology. Tumors exhibit substantial heterogeneity, and thus, it is advantageous for each tumor to serve as its own control. Longitudinal studies in individual tumors enjoy three primary benefits: i) the need for fewer animals, ii) as a corollary, the need for less reagent (therefore, rare and costly drugs and antibodies can be screened more efficiently), iii) more robust statistics. Ultrasound imaging can be particularly effective for monitoring tumor growth in rodents without the need for transfection with reporter genes. This is vital to several investigators since they intend to evaluate primary tumors for comparison with patient therapeutic outcome. Any transfection and clonal selection inevitably deviates from the characteristics of a primary tumor. In addition, the Vevo 770(R) will allow assessment of vascular development and response to vascular disrupting therapies. Each of these goals could also be achieved by MRI, but ultrasound is a much cheaper modality and can facilitate higher throughput of animals. Moreover, UT Southwestern only provides MRI outside the specific pathogen free (SPF) vivarium, which potentially compromises health of animals during longitudinal studies. Several investigators use orthotopic tumor models which currently require invasive procedures for implantation. Image guidance using the Vevo 770(R) promises more effective needle insertion and less invasive tumor implantation. All investigators use mouse models, but several also use rats. An additional goal is the development of ultrasound guided therapeutics including microbubbles. In demonstrations, the Vevo 770(R) is a particularly elegant and well designed instrument including secondary capabilities such as three dimensional volume measurements and rendering. While the Vevo 770(R) is relatively cheap, it is beyond the scope of individual investigators, and this shared instrument will facilitate new experiments, while being efficiently used. Ultrasound use and image interpretation can be complex, but the centralized infrastructure provided by the SAIRP will ensure efficient application, oversight, and continuity.
Ultrasound offers unique capabilities for investigating tumor development in terms of anatomy and perfusion. The new instrument will accelerate development of new therapies in our institution, which will be directly translatable to the clinic, and thus, provide more effective future therapy for patients. It will serve multiple research groups in the preclinical setting, but we believe the results achieved should provide insight into optimizing therapy protocols for patients.
