Imaging Core

这一核心的总体目标是用现有的小动物支持4个项目的具体目标 成像技术，并推进这项技术，以增强未来在癌症研究中的实用价值。小动物 近年来，随着越来越多的人类动物模型的出现，成像变得相当重要 癌症已经成为可能。影像对肿瘤的发展和治疗效果有许多科学依据 和经济优势，如在不同疾病阶段牺牲动物和进行身体解剖和 组织病理学研究可以大幅减少。光学技术已被证明特别有价值 当应用于小动物成像时，因为大量的光学标记(内源和 外源性)，可以在细胞和分子上靶向和可视化各种与癌症相关的过程 具有相对较高灵敏度的水平。然而，到目前为止，大多数光学成像研究只是探索 不需要三维重建的整个动物表面成像。这限制了准确的定位和 量化观察到的动物体内的影响。 这个核心集中在各种光学成像方法上，这些方法可以提供三维功能 关于血液依赖参数的高时间分辨率信息，如血氧、脱氧和总 血红蛋白、绿色荧光蛋白等荧光标记物，以及荧光素酶等生物发光探针。成象 将提供包括用于高空间分辨率(0.1微米以上)的双光子显微镜的系统 到600微米深度)血流动力学效应成像和原位荧光探针；两个动态光学 一种无创全动物层析成像装置及频域光学层析成像系统 吸收成像；Xenogen IVIS 200全动物荧光和生物发光系统 成像。加上9.4T磁共振成像系统，提供高分辨率的解剖 小动物的图像，核心将使研究人员能够研究缺氧对肿瘤发展的影响， 激活的肌成纤维细胞的迁移，骨髓募集，以及肿瘤的生长和消退。 除了应用现有的光学技术，核心还将推动成像科学在 它本身。首先，我们将开发新颖的、高精度的三维图像重建能力 现有的Xenogen IVIS 200生物发光成像仪。第二，我们将调整和优化层流光学 体层摄影术(LOT)在消化系癌症研究中的应用。LOT有望成为一种可行的光学成像 可提供对组织深度为2-3毫米的吸收和荧光成像的模式 200微米分辨率。如果成功地应用于癌症成像，这种模式将填补一个重要的利基市场 在高分辨率双光子显微镜系统和全动物光学成像设备之间。

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.