The overall goal of this core is to support the specific aims of the 4 projects with existing small animalimaging technology and to advance this technology to enhance future utility in cancer research. Small animalimaging has gained considerable importance in recent years as more and more animal models for humancancers have become available. Imaging of tumor development and effects of treatments has many scientificand economical advantages, as sacrificing animals at various disease stages and performing necropsy andhistopathological studies can be sharply reduced. Optical techniques have proven to be especially valuablewhen applied to small animal imaging because of an abundance of optical markers (endogenous andexogenous) that can target and visualize various cancer related processes on the cellular and molecularlevel with comparatively high sensitivities. However, to date most optical imaging studies have only exploredwhole animal surface imaging without 3-dimensional reconstructions. This limits accurate localization andquantification of observed effects inside the animal.This core focuses on various optical imaging methods that can provide 3-dimensional functionalinformation at high temporal resolution about blood-dependent parameters such as oxy, deoxy, and totalhemoglobin, fluorescent markers such as GFP, and bioluminescent probes such as luciferase. Imagingsystem that will be made available include a two-photon microscope for high-spatial-resolution (<0.1 mu m upto depth of 600 mu m) imaging of hemodynamic effects and fluorescent probes in situ; two dynamic opticaltomography devices and one frequency-domain optical tomography system for non-invasive whole-animalabsorption imaging; and a Xenogen IVIS 200 system for whole-animal fluorescence and bioluminescenceimaging. Together with a 9.4 T magnetic resonance imaging system, which delivers high-resolution anatomicalimages 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 initself. First, we will develop novel, highly accurate, three-dimensional image reconstruction capabilities forthe existing Xenogen IVIS 200 bioluminescence imager. Second, we will adapt and optimize laminar opticaltomography (LOT) for applications in digestive cancer research. LOT promises to be a viable optical imagingmodality that can provide absorption and fluorescence imaging of tissues to depths of 2-3mm with 100 to200 mu m resolution. If successfully applied to cancer imaging, this modality would fill an important nichebetween the high-resolution two-photon microscope systems and the whole-animal optical imaging devices.
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