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，旨在开发用于生物医学和制药研究界的多光谱光学断层扫描小动物成像系统。它将把CRI在多光谱、平面小动物成像（通过开发Maestro（tm）系统）方面获得的经验与新颖的高光谱光学层析成像算法结合起来，并将采用独特的光学设计来实现。本提案的主要目的是改进小动物体内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定量的、深度分辨的成像至关重要。该项目的合作伙伴包括光学设计、算法开发、染料化学、先进小动物疾病模型的领导者以及动物成像设施的负责人。关键特性包括：1)在存在显著的自身荧光的情况下，使用具有无与伦比灵活性的光谱可调滤波器进行多路荧光团信号检测；2)一种新颖的光学，可以实现多视图检测；3)定制化多光谱荧光标签策略；4)不要求相机或主体移动，在玻璃板之间压缩主体，或将主体浸入指数和散射匹配的流体中。第一阶段将完成：使用现成的光学元件构建第一代仪器；辐射特性;并通过模拟确认仪器将以2毫米或更好的分辨率完成3D重建。第二阶段将致力于构建第二代仪器，配备定制的高效光学器件，并将增加各种重要的算法、计算和试剂组件，以获得最佳性能，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、肺病、心脏病和血管疾病，并将Maestro-3D的性能与竞争性光学和非光学成像方式进行比较。此外，CRI将研究加快耗时的层析重建的方法。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.