Preclinical Optical Imaging System Scintillator and Pinhole Insert

描述(申请人提供)：临床前分子成像用于研究人类疾病的动物模型，评估新的治疗药物，以及开展基础生物学研究。光学成像技术，如生物发光成像和多光谱荧光成像，目前被广泛用于临床前功能成像，尽管它们在定量、分辨率和灵敏度方面存在深度相关的限制。核成像技术，SPECT和PET，更接近于平移。专用的临床前SPECT和PET系统提供了相当好的成像能力，但可能昂贵，困难(对于非专家)，并且使用缓慢。光学系统随处可得，价格相对低廉，易于操作，而且速度快(用于设置、成像和数据分析；即高通量)。对于一些成像任务，专用的SPECT系统将是必不可少的，但对于许多研究来说，高通量获取投影图像就足够了，从成本降低和速度中获得的收益可能是显著的。用针孔准直器和大面积CsI：Tl闪烁体改装小型动物光学成像系统(如IVIS光谱(Perkin-Elmer))，可获得高分辨率的伽马射线发射放射性示踪剂平面图像 形态新颖。辐射监测器件(RMD)的最新进展导致了CsI(Tl)的厚、透明、晶体微柱结构(CMS)闪烁探测器，它同时提供了高的伽马射线吸收效率、高的本征空间分辨率和明亮的光发射。使用现有的商业临床前光学成像系统快速获取一个或可能多个动物的具有良好空间分辨率的平面伽马图像的能力将是高通量筛选分子成像探针的新的有用工具。在许多现有的临床前光学成像系统上增加核成像能力是一个极具吸引力的机会，可以极大地扩大这种分子成像方式的使用范围。这项提议的目标是建造一个可放置在现有光学成像系统中的插件并对其进行表征，其中插件使用准直器和闪烁体，以使现有的灵敏CCD相机能够对伽马射线进行成像。使用的准直器将来自商业SPECT成像系统。在这个项目中，我们将：(1)制定生产大(直径15厘米)厚(可达4毫米)CMS CsI(Tl)薄膜的协议；(2)使用GATE软件包模拟准直器和探测器的配置；(3)生产用于光学系统插件的三个大型CMS探测器；(4)为各种准直器和闪烁体制造具有灵活几何形状的插件 (5)进行两项概念验证动物成像研究，以展示动态成像和小视场高分辨率成像的潜力。

DESCRIPTION (provided by applicant): Preclinical molecular imaging is used in studying animal models of human disease, evaluating new therapeutic drugs, and in carrying out research in basic biology. Optical imaging techniques, such as bioluminescence and multispectral fluorescence imaging, currently are widely used for preclinical functional imaging despite their depth dependent limitations on quantitation, resolution and sensitivity. Nuclear imaging techniques, SPECT and PET, are more closely translational. Dedicated preclinical SPECT and PET systems provide quite good imaging capability, but can be expensive, difficult (for non-experts), and slow to use. Optical systems are widely available, relatively affordable, easy to operate, and quick (for setup, imaging, and data analysis; i.e. high-throughput). For some imaging tasks a dedicated SPECT system would be essential, but for many studies a high-throughput acquisition of projection images would be sufficient and gains from cost reduction and speed could be significant. High resolution planar images of gamma-ray emitting radiotracers can be obtained by retrofitting a small animal optical imaging system (such as an IVIS Spectrum (Perkin-Elmer)) with a pinhole collimator and a large area CsI:Tl scintillator with a novel morphology. Recent progress at Radiation Monitoring Devices (RMD) has led to thick, transparent, crystalline microcolumnar structure (CMS) scintillator detectors of CsI(Tl) that simultaneously provide high gamma-ray absorption efficiency, high intrinsic spatial resolution, and bright light emission. The ability to use an existing commercial preclinical optical imaging system to rapidly acquire planar gamma ray images with good spatial resolution of one or possibly multiple animals would be a new and useful tool for high throughput screening of molecular imaging probes. Adding a nuclear imaging capability to the many existing preclinical optical imaging systems is an appealing opportunity for greatly expanded access to that modality of molecular imaging. The goal of this proposal is to build and characterize an insert which can be placed in an existing optical imaging system, where the insert uses a collimator and scintillator to enable gamma rays to be imaged by the existing sensitive CCD camera. The collimators used will be from a commercial SPECT imaging system. In this project we will: (1) develop protocols for production of large (15 cm diameter) thick (up to 4 mm) CMS CsI(Tl) films with improved light transmission; (2) simulate collimator and detector configurations using the GATE software package; (3) produce three large CMS detectors for use in an optical system insert; (4) fabricate an insert with flexible geometry for a variety of collimator and scintillator configurations, and perform phantom imaging studies to characterize the system; and (5) conduct two proof-of-concept animal imaging studies to demonstrate the potential for dynamic imaging and for high resolution imaging of a smaller field of view.