7. Project Summary. We seek funds to replace a workhorse instrument—a high-frequency ultrasound and photoacoustic imaging system that is vital to sustaining exceptional productivity of a large and diverse portfolio of biomedical research at UC San Diego. Photoacoustic imaging is an optical technique that converts incident excitation light into acoustic waves; it melds the contrast and spectral behavior of optics with the spatial/temporal resolution and penetration depth of ultrasound. The only photoacoustic scanner in San Diego is at UCSD and was purchased in 2016 under an S10 grant. This existing scanner has yielded extraordinary value: three-fold more publications per year than any other S10-supported photoacoustic instrumentation over the last ten years. However, the scanner is now at the end of its five-year lifespan and has developed devastating reliability issues and will soon no longer be supported by the manufacturer. Therefore, we have an urgent need to replace this scanner and thus maintain and expand the research productivity of our user group. We propose to replace our nearly defunct VisualSonics 2100 + LAZR with a VisualSonics 3100 + LAZR-X Imaging System for dedicated small animal imaging. VisualSonics is the only option for high frequency (>40 MHz) imaging, which is critical for our users who study cardiovascular disease, cancer, and other diseases in rodent models (small animals = small organs = small feature sizes = need for better spatial resolution = need for high frequency). This same scanner will provide a suite of cardiac and vascular imaging tools (e.g., strain, ejection fraction, myocardial velocity) in addition to photoacoustic imaging. Thus, this is two scanners in one, which allows us to double our user base at no additional cost. Our user group includes researchers studying cardiovascular, pulmonary, and vascular disease (Christman, Contijoch, Dillmann, Makino, Pilz, Shyy, Villarreal, Webster, Yuan); cancer biology, detection, and treatment (Engler, Jokerst, Steinmetz, Wang, Webster); and researchers developing new materials for biomedical applications (Christman, Engler, Jokerst, Kwon, Steinmetz, Zhang). This scanner is a good investment for NIH for several reasons: 1) our well-documented record of productivity with prior S10 funds and other federal grants; 2) the technical expertise of the PI and main users who collectively published 80+ papers in photoacoustics and cardiovascular ultrasound; 3) our large and robust user group (15 PIs; 33 grants; 18 R01s); and 4) UC San Diego’s strong commitment to commissioning and operating the scanner throughout its lifetime as exemplified by $110,000 in matching funds and dedicated space with technician. This equipment will empower and accelerate our NIH-funded active research as well as enable a vast array of new studies in cancer, cardiology, inflammation, and neurology.