SUMMARY The Bioimaging Core (BIC) in the Columbia University Digestive and Liver Disease Research Center (CU- DLDRC) will make essential contributions for the understanding and treatment of digestive diseases. State-of- the-art imaging can resolve the complex interactions between cells, organs, metabolites and microbiota that regulate digestive health and disease. However, the cost and expertise of maintaining and operating complex imaging platforms are beyond the financial and technical means of most individual laboratories. The overall goal of the BIC is to provide CU-DLDRC members with state-of-the-art imaging platforms to study mechanisms of digestive health and disease in small animals and human biospecimens in vitro and in vivo, providing resolutions ranging from nanometers to centimeters. The BIC is organized into two units with high-end digestive-focused imaging capabilities backed by expert technical assistance, each led by a highly qualified director with longstanding experience in imaging and core administration. The Microscopy Unit, overseen by BIC Co-Director Liza Pon, provides access to a sophisticated suite of microscopes, including single, multiphoton and spinning disk confocal, super-resolution and total internal reflection fluorescence microscopy, which allow rapid and high- resolution imaging of living or fixed digestive tissue specimens. The Small Animal Imaging Unit, overseen by BIC director Ken Olive, provides access to high-end magnetic resonance imaging, ultrasound, X-ray computed tomography, and optical imaging instruments for imaging of digestive organs and their functions in small animals. In addition, the BIC will develop new digestive-focused imaging modalities, including (i) imaging mass spectrometry with CU-DLDRC member Brent Stockwell for high resolution imaging of metabolites in digestive tissue; and (ii) SCAPE imaging, a novel meso-scale optical platform based on endogenous tissue fluorescence, engineered by CU-DLDRC member Elizabeth Hillman. The Small Animal Imaging unit will also develop novel applications specific for the assessment of gastrointestinal motility, fibrosis, inflammation, tracking of engineered microbes, and in vivo measurement of metabolites. The BIC will contribute to the overall mission of the CU- DLDRC through the following interrelated Aims: To analyze cellular structures and processes that regulate epithelial health in digestive tissues via microscopy (Aim 1); to provide in vivo small animal imaging technologies for the study of digestive physiology and disease (Aim 2); and to provide hands-on training and education in advanced digestive imaging applications (Aim 3). BIC will be a highly utilized resource with 43 out of the 49 CU- DLDRC members (88%) planning to use its services. Via multicore workflows, BIC will closely link to the other CU-DLDRC biomedical cores, thus providing CU-DLDRC members with easy access to imaging clinical biospecimens and organoids, or combining their imaging wit...