Improved Molecular Imaging with SPECT

描述(申请人提供)：小型实验动物的分子成像，如小鼠和大鼠，是研究疾病的重要工具。人类疾病的小鼠模型，如癌症、帕金森氏病和阿尔茨海默病，正在为这些疾病和许多其他疾病的病因、诊断和治疗提供重要线索。超高分辨率PET和SPECT使小动物体内的生化过程可视化成为可能。尽管针孔SPECT获得了重要的结果，但很明显，SPECT系统的灵敏度是次优的。可以通过增加针孔直径(导致分辨率降低)或增加注射剂量(这可能会导致受试者受到辐射损伤)来恢复某些敏感性。该项目将开发新的、广泛适用的、非侵入性的小动物SPECT方法，使用多针孔技术来改善图像统计，同时保持空间分辨率，并潜在地减少对动物的辐射剂量。将研究各种多针孔配置，包括重叠(其中投影图像与探测器表面重叠)和非重叠(其中针孔的几何布置被设计为在探测器上产生单独的图像)。蒙特卡罗计算机模拟将用于优化针孔布置，提供高分辨率图像，而不会影响信噪比或引入图像伪影。最优设计将依赖于应用，并使用定量技术和霍特林观察者研究来确定。其他图像重建方面的改进，例如对晶体中相互作用深度的校正，以及针孔间隔边缘穿透，将使用蒙特卡罗模拟进行研究。将开发基于模型的迭代重建技术来解构来自多针孔系统的数据，并结合针孔边缘穿透和相互作用深度的校正。将构建优化的多针孔系统，并在体模和动物研究中与单针孔装置进行比较，以验证多针孔方法，并测试重建算法。本申请中提出的成像技术的改进将导致灵敏度的提高，并由于所需成像时间的减少而提高小动物分子成像的吞吐量。它还利用了对现有临床SPECT机器的改造，而不是开发专门的小动物成像系统，这使得它的成本更低，应用范围更广。

DESCRIPTION (provided by applicant): Molecular imaging of small laboratory animals, such as mice and rats, is a vital tool in the study of disease. Mouse models of human diseases, such as cancer, Parkinson's disease, and Alzheimer's disease, are providing important clues to the causes, diagnosis and treatment of these, and many other, disorders. Ultra-high resolution PET and SPECT have enabled the visualization of biochemical processes in vivo in small animals. Despite the important results obtained using pinhole SPECT, it is clear that the sensitivity of SPECT systems is sub-optimal. Some sensitivity can be recovered by either increasing the pinhole diameter, resulting in a loss of resolution, or increasing the injected dose, which may lead to radiation damage in the subject. This project will develop novel, widely applicable, non-invasive methods for small animal SPECT, using multiple-pinhole techniques to improve the image statistics, while maintaining the spatial resolution, and potentially reducing the radiation dose to the animal. Various multiple-pinhole configurations will be investigated, including both overlapping (in which the projection images overlap on the detector face), and non-overlapping (in which the geometric arrangement of pinholes is designed to produce separate images on the detector). Monte Carlo computer simulations will be used to optimize the pinhole arrangement, providing high-resolution images, without compromising the signal-to-noise ratio or introducing image artifacts. The optimum design will be application-dependent, and determined using quantitative techniques and Hotelling observer studies. Additional image reconstruction improvements, such as correction for depth-of-interaction in the crystal, and pinhole septal edge penetration, will be investigated using Monte Carlo simulations. Model-based iterative reconstruction techniques will be developed to deconstruct the data from the multiple-pinhole systems, and to incorporate the corrections for pinhole edge penetration and depth of- interaction. The optimized multiple-pinhole system will be constructed and compared against the single pinhole device in both phantom and animal studies, to validate the multiple-pinhole approach, and to test the reconstruction algorithm. The improvements in the imaging technology proposed in this application will lead to enhanced sensitivity, and improvements in the throughput of small animal molecular imaging due to the decreased imaging time required. It also takes advantage of adapting existing clinical SPECT machines, rather than developing a dedicated small animal imaging system, which makes it much less expensive and more widely available.