High-resolution focusing optics for small animal radionuclide imaging

描述（由申请人提供）：小动物模型的非侵入性成像有可能使各种人类条件的生物医学研究的各个领域受益。高分辨率计算机断层扫描和磁共振成像提供了低至10微米尺度的信息，但主要用于可视化结构和解剖结构。小动物放射性核素成像技术，如生理功能和代谢过程的microSPECT和microPET成像，但从根本上限制了约1 mm的空间分辨率。为了克服这些限制，该项目将开发一种新的方法，以进行放射性核素成像的完整动物在空间分辨率约5- 10倍优于目前的方法。这种新方法依赖于掠入射反射镜，其反射和聚焦伽马射线以形成图像，而不使用损害当前技术的空间分辨率和检测灵敏度的吸收准直。因此，该项目将测试开发具有100微米空间分辨率的放射性核素成像系统的可行性，用于使用常用的标记有1-125或Tc-99 m的放射性药物来可视化小鼠的功能和生物分子过程。该项目的具体目标如下：（1）将进行射线跟踪研究，以开发优化几何效率的光学设计，用于对来自Tc-99 m或1-125的低能光子进行成像，目标是实现100微米的空间分辨率和1-2厘米的视场。(2)两个原型透镜，一个设计用于1-125，另一个设计用于Tc-99 m，将通过电铸复制工艺制造。(3)每个透镜将配置有耦合到电子倍增CCD检测器的Csl闪烁体磷光体以表征它们的光学性质（例如，空间分辨率和灵敏度）。(4)将进行平面体模研究，以确定图像重建的最佳方法，并证明其对小鼠的显微γ射线成像的潜力。该项目的长期目标是开发一种体内伽马射线显微镜系统，该系统具有100微米的空间分辨率，高灵敏度和宽视场（FOV），能够可视化小动物的生物分子过程。这种成像能力对于开发新疗法和了解心脏病和癌症等各种人类疾病的疾病进展至关重要。

DESCRIPTION (provided by applicant): Noninvasive imaging of small animal models has the potential to benefit every area of biomedical research for a diverse range of human conditions. High-resolution computed tomography and magnetic resonance imaging provides information down to size scales of 10 microns, but primarily are used to visualize structure and anatomy. Small animal radionuclide imaging techniques such as microSPECT and microPET imaging of physiological function and metabolic processes, but are fundamentally limited to spatial resolutions of approximately 1 mm. To overcome these limitations, this project will develop a new method to perform radionuclide imaging of intact animals at spatial resolutions approximately 5- to 10-fold better than current methods. This new approach relies on grazing incidence mirrors that reflect and focus gamma-rays to form an image without using absorptive collimation that compromises the spatial resolution and detection sensitivity of current techniques. The project therefore will test the feasibility of developing a radionuclide imaging system with 100 micron spatial resolution for visualizing function and biomolecular processes in mice using commonly available radiopharmaceuticals labeled with 1-125 or Tc-99m. The specific aims of the project are as follows: (1) Ray-tracing studies will be performed to develop optical designs that optimize the geometric efficiency for imaging the low-energy photons from Tc-99m or from 1-125, with the goal of achieving a spatial resolution of 100 microns and a 1-2 cm field of view. (2) Two prototype lenses, one designed for 1-125, another engineered for Tc-99m will be fabricated via an electroforming replication process. (3) Each lens will be configured with a Csl scintillator phosphor coupled to an electron multiplying CCD detector to characterize their optical properties (e.g., spatial resolution and sensitivity). (4) Planar phantom studies will be undertaken to determine the best methods for image reconstruction and to demonstrate its potential for microscopic gamma-ray imaging of mice. The long-term goal of this project is to develop an in vivo gamma-ray microscopy system that has 100 micron spatial resolution, high sensitivity and a wide field of view (FOV) capable of visualizing biomolecular processes in small animals. This imaging capability is crucial for the development of novel therapies and understanding the progression of disease for a wide range of human conditions like heart disease and cancer.