High-Resolution SPECT for Molecular Imaging

描述(由申请人提供)： 该项目的长期目标是开发先进的Mu/SPECT/CT分子成像技术，包括最先进的创新Mu/SPECT系统和精确的定量针孔和多针孔SPECT成像技术，提供低至约0.5 mm的超高分辨率和约2cps/mU/Ci的检测效率。为了评估新的fSPECT/CT技术，我们建议进行模拟以及实验模型和小动物成像研究。针对评论者认为先前的建议过于分散的主要问题，我们重新设计了MU/SPECT系统的配置，使用固定角度的探测器组件而不需要经过原型阶段，利用最新的高性能但坚固的探测器技术构建了独特的“角度探测器模块组件”，取消了使用标准伽马相机系统的平面多针孔成像进行纵向断层扫描的研究，删除了两项小型动物成像研究以专注于研究最重要的应用于小鼠斑块的成像，并改用具有稳定和不稳定斑块的更简单的转基因小鼠模型。此外，来自多针孔图像重建、针孔SPECT数据的蒙特卡罗模拟以及使用99mTC Hynic-Annexin V的转基因小鼠斑块成像的额外初步数据也加强了这项提议。研究团队由2组研究人员和3名具有相关专业领域的关键顾问组成。修订的具体目标是：(1)开发用于AIM#5中的MU/SPECT/CT系统的最先进的角度探测器模块和单针孔和多针孔准直以及X射线成像设备，(2)开发3D SPECT成像模拟软件，其模拟闪烁相机模块的性能特征、单针孔和多针孔准直器的设计参数以及SPECT系统的几何和配置，(3)开发用于单针孔和多针孔SPECT的3D定量SPECT图像重建方法，具有衰减、散射和准直器响应的校正，用于准确地对活体中的放射性进行绝对定量，(4)开发简单、准确和稳健的单针孔和多针孔SPECT系统校准方法；(5)开发包括在AIM#1中开发的两个角度探测器组件和将安装在商业级CT支架上的现有MU/CT系统的原型MU/SPECT/CT系统；(6)评估针孔SPECT成像技术和MU/SPECT/CT系统在使用99mTc标记的Annexin-V标记的转基因小鼠模型中成像稳定和易损斑块的能力。

DESCRIPTION (provided by applicant): The long-term goal of this project is to develop an advanced mu/SPECT/CT molecular imaging technology including a state-of-the-art innovative mu/SPECT system and accurate quantitative pinhole and multi-pinhole SPECT imaging techniques that provide ultra-high-resolution down to approximately 0.5 mm and detection efficiency on the order of 2 cps/mu/Ci. To evaluate the novel fSPECT/CT technology, we propose to perform simulations as well as experimental phantom and small animal imaging studies. To respond to the main concern of the reviewers that the previous proposal was too diffuse, we have refocused the research by redesigning the mu/SPECT system configuration with a fixed-angled detector assembly without going through the prototype stage, constructing the unique 'angled detector module assembly' with the latest high performance but robust detector technologies, eliminating the longitudinal tomography study using planar multi-pinhole imaging with standard gamma camera system, deleting two small animal imaging studies to focus on the most important application to imaging of plaques in mice, and switching to a simpler transgenic mouse model with stable and unstable plaques. Also, the proposal is strengthened by additional preliminary data from multi-pinhole image reconstruction, Monte Carlo simulation of pinhole SPECT data, and plaque imaging in transgenic mice using 99mTc Hynic-Annexin V. The team of investigators is streamlined with 2 groups of investigators and 3 key consultants with relevant areas of expertise. The revised specific aims are: (1) to develop a state-of-the-art 'angled' detector module and single and multiple pinhole collimation and an x-ray imaging device for use in the mu/SPECT/CT systems in Aim #5, (2) to develop simulation software for 3D SPECT imaging that models performance characteristics of the scintillation camera modules, design parameters of single and multiple pinhole collimator, and the SPECT system geometry and configuration, (3) to develop 3D quantitative SPECT image reconstruction methods for single and multiple pinhole SPECT with correction of attenuation, scatter and collimator response for accurate absolute quantitation of radioactivity in vivo, (4) to develop simple, accurate and robust calibration methods for single and multi-pinhole SPECT systems, (5) to develop a prototype mu/SPECT/CT system that includes two angled detector assemblies developed in Aim #1 and an existing mu/CT system that will be mounted on a commercial grade CT gantry, and (6) to evaluate the pinhole SPECT imaging techniques and the mu/SPECT/CT system in imaging stable and vulnerable plaques in a transgenic mouse model using 99mTc labeled Annexin-V.