The recent explosion in the availability of defined genetic rodent models, mostly murine but also rat, has led to considerable advances in molecular physiology. The challenge with rodent physiology models is one of scale - how to perform precise in vivo measurements that yield quantitative and meaningful data. This proposal requests funding for a state-of-the-art Small Animal Ultrasound Micro-lmager - the VisualSonics Vevo 770. The instrument will be managed and operated by the Small Animal Hemodynamic Core Facility within the Division of Cardiology at UCHSC. The instrument will be used by an interdisciplinary group of NIH-funded investigators within the University of Colorado campuses. Eleven major users of the instrument are located on the Health Sciences Center campus and one investigator is located on the Boulder campus. Several minor users of the instrument are also located on these campuses. This group of investigators has an extensive history of productive collaborations. Research projects benefiting from the acquisition of this instrument can be broadly defined as follows: (1) rodent models of heart failure; (2) pulmonary hypertension and right ventricular function; (3) renal regulation of hemodynamics; and (4) therapeutic applications of stem cells. Ultrasound images are currently being acquired with a 6-year-old VingMed clinical echocardiographic machine equipped with a 10 MHz linear array probe. The Vevo 770, which has a resolution of 30-70um, is an ultrasound instrument developed for use in small animals. Purchase of this instrument will greatly extend the ultrasound capabilities available to the Core users and ensure that future in vivo imaging needs will be met for years to come. Anticipated uses for the Vevo 770 include determination of cardiac wall motion abnormalities and calculation of ejection fraction in mice using 2-D imaging modalities; measurement of cardiac output in mice and rats using Pulse-Wave Doppler; quantitation of right ventricular function by M- mode and 2-D imaging modalities in mice and rats; image guided injection of stem cells into embryonic and adult mice; and renal blood flow in mice and rats. The use of transducers with specific focal lengths and axial resolution enhances the adaptability of this instrument to different research applications. We anticipate that the enthusiasm for use of this instrument will only increase over time as more investigators move to small animal model systems to further define molecular interactions in an in vivo setting. ? ?