Development and Integration of Bioluminescent CT

描述(由申请人提供)： 小动物，特别是基因工程小鼠，对于理解病理性疾病表现的生物学基础越来越重要。正在作出重大努力，在形式和功能上将基因组与表型表达联系起来(“生理组”)。小动物成像提供了在非常压缩的时间范围内评估病理进展的机会，并且分辨率大大提高。在这份R21/R33提案中，我们计划开发和集成第一台用于基因表达成像的生物发光CT(BLCT)设备和一台最先进的微型CT扫描仪，用于活体小鼠模型的肺研究。我们的长期目标是推动分子和显微成像技术的发展，并使所提出的集成系统成为生物医学应用的体内工具，特别是小动物断层扫描。R21阶段的具体目标是：(1)开发用于小鼠肺的生物发光成像的数据采集模块；(2)基于从CT体积得出的小鼠的光学特性建立生物发光的正演模型；(3)在数值模拟和体模实验中论证生物发光层析成像的可行性。R33阶段的具体目标是：(1)用I0 CCD相机制作生物发光CT设备的原型，并开发空间分辨率在1ram数量级的迭代算法；(2)建立具有双成像功能的多分辨率Micro-CT扫描仪，并开发高质量重建的解析算法，包括体内模式，空间分辨率约为20微米，时间分辨率约为20秒，最大空间分辨率约为5微米；(3)整合两种尖端CT模式(光学和X射线)，并展示集成系统在小动物研究中的可行性和实用性。在R21/33项目完成后，将开发出具有分子、多分辨率、多能量、动态和生物发光成像能力的独特微层析成像系统。我们将通过实例项目演示该系统在生成关键的肺部生理和病理信息方面的效用。

DESCRIPTION (provided by applicant): Small animals, particularly genetically engineered mice, are of increasing importance to understand the biologic basis for pathologic disease manifestations. Major efforts are being made to link the genome to the phenotypic expression in both form and function ("Physiome"). Small animal imaging offers the opportunity to evaluate pathologic progression in a much-compressed time frame and with a much-improved resolution. In this R21/R33 proposal, we plan to develop and integrate the first bioluminescent CT (BLCT) device for imaging gene expression and a state-of-the-art micro-CT scanner for studies of the lung in the living mouse model. Our long term goal is to advance molecular and micro imaging technology, and make the proposed integrated system an in vivo tool in biomedical applications, especially for small animal tomography. The specific aims of the R21 Phase are to (1) develop a data acquisition module for bioluminescent imaging of the mouse lung; (2) establish the forward model for bioluminescence based on the optical properties of the mouse as derived from its CT volume; (3) demonstrate the feasibility of bioluminescent tomography in numerical simulation and phantom experiments. The specific aims of the R33 Phase are to (1) prototype a bioluminescent CT device with I0 CCD cameras, and develop an iterative algorithm for a spatial resolution on the order of 1 ram; (2) build a multi-resolution micro-CT scanner with dual imaging, and develop analytic algorithms for high quality reconstructions, including the in vivo mode with about 20 micron spatial resolution and 20 second temporal resolution and a maximal spatial resolution on the order of 5 microns; (3) integrate the two cutting-edge CT modalities (optical and X-ray), and demonstrate the feasibility and utility of the integrated system in small animal studies. Upon completion of the R21/33 project, a unique micro-tomography system will have been developed with molecular, multi-resolution, multi-energy, dynamic and bioluminescent imaging capabilities. We will demonstrate, through example projects, the utility of the system in generating critical physiological and pathological information of the lung.