A major component of basic and translational research involves elucidating the mechanisms underlying tissue regeneration, repair and remodeling during growth and development, for gaining insights into how these processes go awry in pathologic disorders, including inflammation, diabetes and cancer, and for and expediting development of new diagnostics and treatments. Optical imaging in vivo is now recognized as a critical strategy for achieving these goals and for evaluating developmental and disease models. In vivo optical imaging can be broadly classified into bioluminescence imaging and fluorescence imaging. Bioluminescence imaging requires transgenic animals or cells that are genetically engineered to express a luminescent reporter gene such as firefly luciferase that spontaneously generates an optical signal and reports specific gene expression in live animals. Fluorescence imaging requires an external light source for excitation and appropriate emission filters to capture fluorescent emission signals from transgenic animals or cells or from an optical probe that can be injected into the animal. Optical imaging is easy to use with fast acquisitions, straight forward imaging reconstructions and analysis;and it can be operated under high throughput settings. In this proposal, we seek funding to purchase a state-of-the-art Caliper Life Sciences/Xenogen Spectrum Imaging System, which is a multifaceted bioluminescence and fluorescence imaging instrument for noninvasive live small animal imaging, with versatile capabilities to assist investigators to advance biomedical research on the Parnassus Heights Campus of the University of California, San Francisco. This system that is readily used by basic users and has sophisticated and advanced capabilities beneficial to more experienced imaging users. This imaging system incorporates all the requirements for bioluminescence and fluorescence imaging, epi, and trans-illuminations, spectral unmixing and three-dimensional reconstruction of both bioluminescent and fluorescent signals. This instrument offers unique capabilities to remove autofluorescence, improve signal-to-background ratio and allow for simultaneous imaging of multiple fluorophores in a single animal that help researchers to quantify in vivo optical signals, and investigate multiple molecular pathways in a given disease. The advanced technology of this instrument will provide the investigators with the ability to image tissue regeneration and repair events or tumor growth and to visualize trafficking of immune cells, growth and metastasis of small tumors and regenerating pancreatic islets in live animals. The ability to image these events in small animals, and to use imaging data will streamline preclinical therapeutic studies, which have direct translatability to patients. Public Health Relevance: Developing mouse models for diabetes, immune disorders and common cancers are essential to better understand the biology of these diseases and to establish effective preclinical therapies that can be translated to people with comparable disorders. The translational potential of this work will be greatly enhanced by the acquisition of a imaging system. The ability to image tissue repair events, regenerating pancreatic islets or tumor growth noninvasively in small animals will streamline preclinical therapeutic studies, which have direct translatability to patients.
