Spectrally resolved tomographic small-animal fluorescence imager

描述（由申请人提供）：这是一个快速通道提案，旨在开发一种多光谱光学断层扫描小动物成像系统，供生物医学和制药研究界使用。它将结合联合收割机的经验，中国国际研究所已获得的多光谱，平面小动物成像（通过其开发的Maestro（tm）系统）与新的高光谱光学层析成像算法，并将实现使用一个独特的光学设计。该提议的主要目的是改进小动物内的点和扩展荧光源的三维（3D）定位。层析成像方法对于实现真正的定量、深度分辨成像是必不可少的。该项目的合作伙伴包括光学设计，算法开发，染料化学，先进的小动物疾病模型以及动物成像设施的主管。主要特性包括：1）在存在显著的自体荧光的情况下，使用具有无与伦比的灵活性的光谱可调谐滤波器用于多路复用荧光团信号检测; 2）能够进行多视图检测的新型光学器件; 3）定制的多光谱荧光标记策略;以及4）不需要照相机或对象移动，对象在玻璃板之间的压缩，或者将对象浸没在折射率和散射匹配的流体中。第一阶段将实现：第一代仪器与现成的光学构造;辐射特性;表面轮廓测量，并通过模拟确认该仪器将完成3D重建与2毫米或更好的分辨率。第二阶段将致力于构建具有定制高效光学器件的第二代仪器版本，并将添加各种重要的算法，计算和试剂组件以实现最佳性能，重点是定量验证。该系统将部署在几个动物成像设施。将研究各种疾病的动物模型，包括转移性乳腺癌、肺、心脏和血管疾病，并将Maestro-3D的性能与竞争性光学和非光学成像模式进行比较。此外，CRI将致力于加快耗时的断层重建的方法。最后，将开发易于使用的控制、显示、定量和集成到实验室信息系统的软件。

DESCRIPTION (provided by applicant): This is a Fast-Track proposal to develop a multispectral optical tomography small-animal imaging system for use by the biomedical and pharmaceutical research communities. It will combine the experience CRI has acquired in multispectral, planar small-animal imaging (through its development of the Maestro(tm) system) with novel hyperspectral optical tomography algorithms and will be realized using a unique optical design. The primary aim of this proposal is to refine 3-dimensional (3D) localization of point and extended fluorescent sources within small animals. Tomographic approaches are essential for achieving truly quantitative, depth- resolved imaging. Partners in this project include leaders in optical design, algorithmic development, dye chemistry, advanced small-animal models of disease, and directors of animal imaging facilities. Key properties include: 1) the use of a spectrally tunable filter with unmatched flexibility for multiplexed fluorophore signal detection in the presence of significant autofluorescence; 2) a novel optic that enables multi- view detection; 3) a customized multispectral fluorescent label strategy; and 4) no requirement for camera or subject movement, compression of the subject between glass plates, or submersion of the subject in index- and scatter-matching fluids. Phase I will accomplish: construction of a first-generation instrument with off-the-shelf optics; radiometric characterization; surface profilometry, and confirmation via simulation that the instrument will accomplish 3D reconstructions with a resolution of 2 millimeters or better. Phase II will be dedicated to building a second- generation version of the instrument with custom, high-efficiency optics, and will add a variety of important algorithmic, computational and reagent components for optimal performance, with an emphasis on quantitative validation. The system will be deployed at several animal imaging facilities. A variety of animal models of disease, including metastatic breast cancer, pulmonary, cardiac and vascular disease will be studied and the performance of the Maestro-3D compared to competing optical and non-optical imaging modalities. In addition, CRI will work on methods to accelerate time consuming tomographic reconstructions. Finally, easy-to-use software for control, display, quantitation and integration into laboratory information systems will be developed.