High Sensitivity In Vivo Imaging System with Integrated Micro-Computed Tomography for Animal Phenotyping Core

项目摘要。 高灵敏度和微尺度分辨率仪器对于开创性的生物医学研究至关重要。在 活体成像技术对于测量活体动物中的复杂生物过程特别有价值， 跟踪它们随时间的变化，如癌症转移，新药的体积分布和茎的组织归巢 移植后的细胞特别是光学成像，随着技术的发展， 非常有效的荧光染料和纳米颗粒以及基于生物发光酶的工具。体内 通过开发转基因动物和工程化的细胞， 以诱导和条件方式表达荧光或生物发光报告基因， 光学成像在各种研究领域的前所未有的体内应用。这种共享的工具 建议购买光学IVIS SpectrumCT系统（PerkinElmer），该系统将在 波士顿大学医学院的代谢表型和IVIS核心（动物表型核心）。这 核心方案自2011年以来已成功运行，目前为该工具提供技术支持， 18名NIH资助的主要研究者。已经进行了各种开创性的研究项目， 多年来使用动物表型核心的IVIS，包括开发新的货物 用于药物递送的纳米颗粒，癌症进展和转移的分子靶点的发现， 用多能干细胞优化组织归巢和器官再生。新的SpectrumCT是一个 具有用于2D和3D集成微计算机断层扫描的高灵敏度光学成像平台 生物发光和荧光检测以及射线照相（CT）成像。这种最先进的仪器将 替换PerkinElmer不再支持的当前IVIS，同时提供增强的功能， 在多达10只活动物中纵向监测和量化生物过程。新一代IVIS 提供与低剂量CT相结合的快速多成像模式，实现配准和光谱解混 用于高级2D分析和3D重建。除了正在进行的项目，新的IVIS SpectrumCT将 由NIH资助的其他用户使用，以推进他们对骨骼发育的研究，肥胖的影响， 乳腺癌、新型抗生素疗法和其他突破性的研究项目。重要的是 这种体内仪器的可用性将补充离体成像和定量模式，例如 共聚焦显微镜和流式细胞仪，目前可在整个波士顿大学的核心设施 社区，扩大高端仪器工具集的成功至关重要的研究调查。

PROJECT SUMMARY. High-sensitivity and microscale resolution instruments are essential for groundbreaking biomedical research. In vivo imaging technologies are particularly valuable to measure complex biological processes in live animals and track them over time, such as cancer metastasis, volume distribution of novel drugs and tissue homing of stem cells after transplantation. Optical imaging, in particular, has become extremely sensitive with the development of very efficient fluorescent dyes and nanoparticles as well as luciferase-based bioluminescence tools. In vivo spatial targeting of optical signals through the development of transgenic animals and cells that are engineered to express fluorescent or bioluminescent reporters, in both inducible and conditional manners, have enabled unprecedented in vivo applications of optical imaging in a variety of research fields. This shared instrumentation proposal is to purchase the optical IVIS SpectrumCT system (PerkinElmer), which will operate within the Metabolic Phenotypic and IVIS Core (Animal Phenotyping Core) in the Boston University Medical Campus. This Core has been successfully operational since 2011 and currently offers technical support for this instrument to 18 NIH-funded principal investigators. A variety of groundbreaking research projects has been conducted with the use of the Animal Phenotyping Core’s IVIS over the years, including the development of novel cargo nanoparticles for drug delivery, the discovery of molecular targets of cancer progression and metastasis, the optimization of tissue homing and organ regeneration with pluripotent stem cells. The new SpectrumCT is a high-sensitivity optical imaging platform with integrated micro-computed tomography for 2D and 3D bioluminescence and fluorescence detection and radiographic (CT) imaging. This state-of-the-art instrument will replace our current IVIS, which is no longer supported by PerkinElmer, while providing enhanced capabilities for monitoring and quantifying biological processes longitudinally in up to 10 live animals. This new generation IVIS provides fast multi-imaging modality combined with low dose CT, enabling co-registration and spectral unmixing for advanced 2D analysis and 3D reconstructions. In addition to ongoing projects, the new IVIS SpectrumCT will be used by additional NIH-funded users to advance their research on bone development, the effect of obesity on breast cancer, novel antibiotic therapeutics and other groundbreaking research projects. Importantly, the availability of this in vivo instrumentation will complement ex vivo imaging and quantitative modalities, such as confocal microscopy and FACS, currently available in the core facilities across the entire Boston University community, expanding the high-end instrumentation toolset crucial for the success of research investigators.