Recent advances in the instrumentation for medical imaging have produced miniaturized versions of x-ray, radionuclear and magnetic resonance scanners for studies in small laboratory animals. This, coupled with increasingly sophisticated transgenic mouse models, is driving a revolution in the investigation of disease and developmental processes in vivo at the whole-animal level. This proposal requests funding for a high-resolution ultrasound device to facilitate and improve interdisciplinary research in small animals in the areas of cancer and cardiac disease. High-frequency ultrasound is a newly emerging modality with great potential for use in small animal models. By increasing transducer frequencies, engineers have been able to achieve resolution-to-subject size ratios similar to those of clinical ultrasound imaging. As a result, anatomical and physiological (e.g., blood velocity) visualization and measurement capabilities are now fully available for use in small animals. Furthermore, recent development of microbubble technology has provided a very effective means of intravascular contrast enhancement and is being extended to molecular targeting, which could have a major impact on therapeutic delivery. During the last several years, a Molecular Imaging Center has been established at USC with support from an NIH/NCI P20 planning grant. The requested ultrasound scanner will be housed and operated in the Center's Molecular Imaging Laboratory, where it will complement other shared-use devices purchased with previous awards from the NCRR, including small-animal PET, CT and optical imaging systems. . Ultrasound would supplement our existing small-animal imaging capabilities with a non-ionizing radiation modality that would give us real-time, non-invasive anatomic imaging. High- frequency ultrasound imaging would greatly facilitate our use of orthotopic tumor models by allowing image-guided implantation in deep-lying organs and tissues. Other applications in small animal research will include: serial monitoring of tumor growth and tumor response to treatment; image-guided serial biopsy of tumors and implanted organs for ex vivo histopathology and molecular assay; serial assessment of tumor and organ blood supply, as well as evaluation of cardiac function, including left ventricular ejection fraction The requested ultrasound scanner will be used by investigators in the fields of radiology/nuclear medicine, surgery, pathology, biochemistry/molecular biology, pharmaceutical sciences, and biomedical engineering. Addition of the requested instrument will increase the productivity of assembled PHS-funded investigators who are working in various areas of medicine. The discoveries and advancements made by these investigators will ultimately have a direct positive impact on public health. ? ? ?