SUMMARY ABSTRACT We request funds to purchase a new IVIS Spectrum-CT instrument equipped with a thermoelectrically-cooled CCD camera, integrated optical and micro-CT sources and detectors, and 3D diffuse tomographic reconstruction software. The system includes bioluminescent and fluorescent phantom mouse software and a rodent anesthesia system. This instrument will be installed in the Biomedical Imaging Shared Resource (BISR) facility at the Medical College of Wisconsin (MCW). Since its creation in 2004, the BISR has supported the biomedical research programs of a diverse group of NIH-funded investigators at MCW and its partner institutions in the Clinical and Translational Science Institute (CTSI) of Southeastern Wisconsin. Consistent with its record of major investments in medical and biomedical imaging instrumentation and facilities, MCW has committed substantial matching funds to purchase the maintenance contract and provide technical support for the instrument. The IVIS Spectrum-CT provides 2D and 3D quantitative bioluminescence and multispectral fluorescence with low dose computed tomography (CT), spectral unmixing, and Cerenkov imaging currently unavailable in the obsolete optical and micro-CT instruments existing at MCW. Access to the requested fully integrated optical and micro-CT imaging platform will markedly benefit the research projects of eight federally funded (NIH, DOD) Major User investigators and four Minor User investigators as described in this application. These projects will benefit from the requested instrumentation thanks to increased resolution and sensitivity; spatial co-registration across imaging modalities; and the repeatable, non-invasive and minimally-ionizing examination that enables longitudinal imaging to track disease pathogenesis and treatment responses in rodent models. When installed, this instrument will be the only multimodal 3D imaging instrument for in vivo small animal imaging in Milwaukee and southeastern Wisconsin. The BISR is already equipped with the infrastructure and manned by the support staff required for installation and expert operation of the IVIS Spectrum-CT. The new instrument will be maintained by personnel experienced in operating and maintaining in vivo rodent imaging instrumentation, small animal anesthesia, and managing a multi-user recharge facility. Instrument time will be allocated using the existing BISR scheduling system implemented in iLabs. A standing local advisory committee will provide oversight. BISR financial operations are managed by the senior business administrator in the MCW Cancer Center. Acquisition of the IVIS Spectrum-CT instrument requested in this application will have a profound impact on NIH-funded biomedical research programs at MCW and its partner CTSI institutions.