The overall goal of this core is to support the specific aims of the 4 projects with existing small animal imaging technology and to advance this technology to enhance future utility in cancer research. Small animal imaging has gained considerable importance in recent years as more and more animal models for human cancers have become available. Imaging of tumor development and effects of treatments has many scientific and economical advantages, as sacrificing animals at various disease stages and performing necropsy and histopathological studies can be sharply reduced. Optical techniques have proven to be especially valuable when applied to small animal imaging because of an abundance of optical markers (endogenous and exogenous) that can target and visualize various cancer related processes on the cellular and molecular level with comparatively high sensitivities. However, to date most optical imaging studies have only explored whole animal surface imaging without 3-dimensional reconstructions. This limits accurate localization and quantification of observed effects inside the animal. This core focuses on various optical imaging methods that can provide 3-dimensional functional information at high temporal resolution about blood-dependent parameters such as oxy, deoxy, and total hemoglobin, fluorescent markers such as GFP, and bioluminescent probes such as luciferase. Imaging system that will be made available include a two-photon microscope for high-spatial-resolution (<0.1 mu m up to depth of 600 mu m) imaging of hemodynamic effects and fluorescent probes in situ;two dynamic optical tomography devices and one frequency-domain optical tomography system for non-invasive whole-animal absorption imaging;and a Xenogen IVIS 200 system for whole-animal fluorescence and bioluminescence imaging. Together with a 9.4 T magnetic resonance imaging system, which delivers high-resolution anatomical images of small animals, the core will enable researcher to study effects of hypoxia on tumor development, migration of activated myofibroblasts, bone marrow recruitment, and tumor growth and regression. Going beyond applying existing optical technologies, the core will also advance imaging science in itself. First, we will develop novel, highly accurate, three-dimensional image reconstruction capabilities for the existing Xenogen IVIS 200 bioluminescence imager. Second, we will adapt and optimize laminar optical tomography (LOT) for applications in digestive cancer research. LOT promises to be a viable optical imaging modality that can provide absorption and fluorescence imaging of tissues to depths of 2-3mm with 100 to 200 mu m resolution. If successfully applied to cancer imaging, this modality would fill an important niche between the high-resolution two-photon microscope systems and the whole-animal optical imaging devices.
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