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层析成像小动物成像系统，供生物医学和制药研究社区使用。它将把CRI在多光谱、平面小动物成像方面(通过其Maestro(Tm)系统的开发)获得的经验与新的高光谱光学层析成像算法结合起来，并将使用独特的光学设计来实现。这项建议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的定量、深度分辨率成像是必不可少的。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负责人。主要特性包括：1)使用具有无与伦比的灵活性的光谱可调滤光片，用于在存在显著自发荧光的情况下检测多路传输的荧光团信号；2)能够进行多视角检测的新型光学元件；3)定制的多光谱荧光标签策略；以及4)不需要相机或对象移动，不需要在玻璃板之间压缩对象，也不需要将对象浸入折射率和散射匹配的流体中。第一阶段将完成：建造具有现成光学设备的第一代仪器；辐射特性；表面轮廓测量，并通过模拟确认该仪器将以2毫米或更高的分辨率完成3D重建。第二阶段将致力于建造第二代版本的仪器，带有定制的高效率光学元件，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中。将研究各种疾病的动物模型，包括转移性乳腺癌、肺部、心脏和血管疾病，并将Maestro-3D与竞争对手的光学和非光学成像方式进行比较。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、定量和与实验室信息系统集成的软件。

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.