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，对于了解病理性疾病表现的生物学基础越来越重要。目前正在努力将基因组与表型表达的形式和功能联系起来（“生理组”）。小动物成像提供了一个机会，以评估病理进展在一个非常压缩的时间框架，并与一个大大提高了分辨率。在这个R21/R33提案中，我们计划开发和整合第一个用于成像基因表达的生物发光CT（BLCT）设备和最先进的微型CT扫描仪，用于在活体小鼠模型中研究肺部。我们的长期目标是推进分子和显微成像技术，并使所提出的集成系统在生物医学应用中的体内工具，特别是小动物断层扫描。R21阶段的具体目标是：（1）开发用于小鼠肺部生物发光成像的数据采集模块;（2）基于小鼠CT体积的光学特性建立生物发光的正向模型;（3）在数值模拟和体模实验中证明生物发光断层成像的可行性。R33阶段的具体目标是（1）用10 CCD照相机制作生物发光CT设备的原型，并开发空间分辨率为1 mm量级的迭代算法;（2）建立具有双重成像的多分辨率微型CT扫描仪，并开发用于高质量重建的分析算法，包括具有约20微米空间分辨率和20秒时间分辨率以及5微米量级的最大空间分辨率的体内模式;（3）将两种最先进的CT模式（光学和X射线）集成在一起，并证明集成系统在小动物研究中的可行性和实用性。R21/33项目完成后，将开发出一种独特的微型层析成像系统，具有分子、多分辨率、多能量、动态和生物发光成像能力。我们将通过示例项目展示该系统在生成肺部关键生理和病理信息方面的实用性。

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.