The project is a ShEEP request for a Perkin-Elmer IVIS SpectrumCT in vivo Imaging System, which will bring a new capability for performing whole animal imaging studies to the research core laboratories at the Baltimore VA Medical Center. The IVIS SpectrumCT in vivo Imaging System has integrated 2D and 3D optical imaging and microCT modalities; which allow simultaneous molecular and anatomical longitudinal studies, providing researchers with essential insights into complex biological systems in small animal models. The instrument will facilitate individual VA investigators with widely varying projects to perform a variety of whole animal imaging studies. The requested instrument will support the work of the entire Baltimore VA Medical Center Research Service, including six major VA Merit funded users (Drs. Hornyak, Antalis, Hasday, Hu Martin, and Xie, and one minor user (Dr. Raufman). Thomas J. Hornyak, M.D., Ph.D., Associate Chief of Staff (ACOS) for Research and Development (R&D) at the VA Medical Health Center System (VAMHCS) is the Principal Investigator (PI) for this proposal. He is also PI on the Merit Review project,?Melanocyte Stem Cells in Regenerative Medicine?. He and his laboratory will use the IVIS Spectrum CT to track in vivo the survival, localization, and migration of labeled stem cells introduced for regenerative purposes. Thereby, maximizing the amount of information obtained with each individual experiment and thus contributing to more rapid progress. Toni Antalis, Ph.D. is a VA funded investigator whose research seeks to better understand the molecular and cellular processes that regulate thrombus resolution, so that specific therapies to accelerate the resolution process can be developed. Her group will use fluorescent reporter markers to perform 2D and 3D in vivo imaging of animals for this study, allowing for molecular and anatomical non-invasive imaging in mouse models of deep vein thrombosis. Jeffrey Hasday, MD., is a VA Merit funded investigator whose VA Merit project focuses on screening existing small molecules selected to bind to a pocket within the substrate binding groove of p38alpha as a novel therapeutic for acute lung disease. His experimental plan includes testing in a mouse model of acute lung injury induced by intratracheal instillation of endotoxin. The IVIS SpectrumCT system will allow his laboratory to follow mice with sequential measurements of lung permeability using the near-IR probe Angiosense 680 EX. Bingren Hu?s VA Merit research studies novel mechanisms underlying brain ischemia- reperfusion (IR) injury. His laboratory will utilize the IVIS SpectrumCT to study gliosis using glial fibrillary acidic protein (GFAP) luciferase transgenic mice, and brain inflammation using CX3CR1-GFP mice after brain ischemia. They will also use it to study migration and infiltration of inflammatory and immune cells from peripheral organs to the brain in a mouse model of brain ischemia and reperfusion. Stuart Martin, Ph.D.?s funded VA research project uses a novel microfluidic device to rapidly image free-floating breast tumor cells and define phenotypes that are predictive of metastatic potential. These phenotypes are then related to metastatic potential and drug response using clinically-relevant patient-derived xenograft transplants in mice. The requested instrument will be used to quantitatively measure metastatic tumor burden to specific organs in these mice. MDs Guofeng Xie and Jean-Pierre Raufman?s individual work focus on molecular mechanisms behind colon cancer progression. Dr. Xie will use the IVIS SpectrumCT to quantitatively measure tumor progression in live animals using the mouse model of colon cancer metastasis, and to determine if anti-matrix metallo-proteinase 7 (MMP7) antibodies inhibit colon cancer progression. Dr. Raufman will use the requested system for in vivo luciferase bioluminescence luciferase imaging of colon tumor formation and metastasis in his animal model. Using the requested imaging system for longitudinal studies, he can avoid euthanizing mice before a meaningful number of metastases develop. He will also be able to detect lesions too small or deep to be seen by gross post-mortem sectioning ? enhancing his ability to measure a critical endpoint.
The broad, long-term objective of this application is to provide a specialized research instrument to a group of VA research investigators who are conducting VA-funded studies on problems that are relevant to Veteran health. The Perkin-Elmer IVIS SpectrumCT in vivo Imaging System is a user-friendly instrument that will be housed within the laboratory space of the Baltimore VA Medical Center; and will be available for use by VA investigators pursuing projects in many areas including: cancer research, inflammation and lung fibrosis, and acute brain injury. The IVIS SpectrumCT System allows scanning of up to five mice at a time and complete 2D and 3D fluorescence imaging tools allow the user to pinpoint and quantitate specific fluorochromes deep within an animal. Integrated optical imaging and microCT modalites allow simultaneous molecular and anatomical longitudinal studies, providing researchers with essential insights into complex biological systems in small animal models.
