The Jefferson High Frequency Ultrasound Core Facility provides preclinical imaging services to investigators across Thomas Jefferson University (TJU). A Vevo 2100 ultrasound system (FujiFilm VisualSonics Toronto, Ontario, Canada), which was acquired in 2011 under an S10 awarded to Dr Flemming Forsberg (the PI of this application) enables noninvasive high-resolution imaging as well as opto-acoustic quantification of the tissue microenvironment. Frequently used applications include analysis of multiple cardiac functional parameters including ejection fraction, fractional shortening, dimensions, volumes, wall thickness, etc., orthotopic tumor and organ volume quantification, vascularity monitoring, nonlinear contrast imaging, ultrasound-triggered drug delivery work, contrast-enhanced photoacoustic imaging, and quantification of tissue oxygenation levels. Animal models we have imaged range from fruit fly larvae to rabbits, but primarily consist of mice and rats. Over the last decade, the system has been used by more than 20 Jefferson faculty members. These have resulted in a countless publications and ongoing research collaborations. At the current time, the system is utilized by 14 NIH funded investigators and its operation is crucial to the progress of these grants. These investigators span multiple TJU departments including Radiology, Medicine, Orthopedic Surgery, and Pathology. However, VisualSonics has announced that it will no longer provide service on the 2100 model line. Hence, this application requests funding to purchase the newer Vevo 3100 LAZR-X system, which will provide reliable small animal scanning capabilities for the foreseeable future, while also offering significant technological upgrades in multiple areas over the 2100 model. Moreover, we will acquire a pressure-volume loop recording system from Data Sciences International, which uses different implanted monitors to detect in vivo real-physiological parameters, and, most importantly, can be directly linked together with the Vevo 3100 system. All the selected major users of this system have ongoing and well-funded federal research programs that have the current and future needs of in vivo imaging of animal models for translational applications in cancer biology, cardiovascular disease and emerging molecular therapies. The Vevo 3100 ultrasound scanner together with the pressure-volume loop recording system is truly the state-of-the-art in vivo imaging and measurement system dedicated to, and without equal for, small animals. Consequently, these systems will be a major boost to the extensive, federally supported, small animal research efforts at TJU.