IMAGING STRUCTURE AND FUNCTION IN SMALL ANIMALS

描述(逐字摘自申请者摘要)：这项生物工程研究 合作伙伴将开发一种用于高分辨率的双模式CT/SPECT系统 转基因和基因敲除小鼠的放射性核素成像 广泛用于模拟人类的发病机制、诊断和治疗 疾病。这项研究将集中在开发技术，以 相关的结构和功能，并可以执行非侵入性和 组织代谢和器官生理学的定量准确测量 在使用放射性标记示踪剂的小动物身上。在此背景下，这项研究 该计划包括5个具体目标。(1)开发针孔SPECT系统 使用像素化的硅像素阵列和掺铊的碘化铯 (CsI(Tl))小动物放射性核素成像闪烁体。二 将开发可互换的探测器阵列，其中一种用于低能量成像 放射性核素，如‘25I(27.5keV)，另一种用于99mTc(140)成像 Kev)和其他具有较高光子能量的放射性核素。(2)针孔 来自特定目标1的SPECT系统将与计算的锥束集成在一起 断层扫描系统体积，允许连续采集CT和SPECT 在不移动动物的情况下拍摄图像。(3)锥束层析算法将是 用于重建放射性核素和x射线断层扫描数据 来自小动物成像器。将开发的技术将使用 重建CT和SPECT数据以量化区域分布 适用于小鼠的空间分辨率的放射性核素浓度。(4) 将使用双模式成像系统进行活体测量 在转基因小鼠心血管生理学研究中的作用 心脏疾病的交感神经支配。这些测量将测试 交感神经异质性增加的假说与 与充血性心力衰竭的发展有关。(5)双通道成像 系统将用于测量人源化肿瘤和器官的分布 抗HER2单抗在转基因小鼠乳腺转移模型中的应用 癌症。这个项目的总体目标是开发一种高分辨率成像 结合CT和SPECT以关联结构和功能的系统。这个 该系统还将被设计用于在小鼠身上进行非侵入性系列研究，以及 以取代有创的直接组织取样和放射自显影 利用放射性标记示踪剂进行生物分布研究和功能评估 在转基因小鼠身上。

DESCRIPTION (Verbatim from Applicant's Abstract): This bioengineering research partnership will develop a dual-modality CT/SPECT system for high-resolution imaging of radionuclides in transgenic and knockout mice that now are in widespread use to model the mechanism, diagnosis, and treatment of human diseases. This research will be focused on the development of techniques that correlate structure and function, and that can perform noninvasive and quantitatively accurate measurement of tissue metabolism and organ physiology in small animals using radiolabeled tracers. Within this context, the research program includes 5 specific aims. (1) A pinhole SPECT system will be developed using a pixellated silicon pixel array and thallium-doped cesium iodide (CsI(Tl)) scintillator for radionuclide imaging of small animals. Two interchangeable detector arrays will be developed, one for imaging low-energy radionuclides such as '25I (27.5 keV), and the other for imaging 99mTc (140 keV) and other radionuclides having higher photon energies. (2) The pinhole SPECT system from Specific Aim 1 will be integrated with a cone-beam computed tomography system volume to allow sequential acquisitions of CT and SPECT images without moving the animal. (3) Cone-beam tomographic algorithms will be implemented for reconstruction of the radionuclide and x-ray tomographic data from the small animal imager. Techniques will be developed that use the reconstructed CT and SPECT data to quantify regional distribution of radionuclide concentration at spatial resolutions suitable for mice. (4) The dual-modality imaging system will be used for in vivo measurement of cardiovascular physiology in transgenic mice to investigate the role of the sympathetic innervation in heart disease. These measurements will test the hypothesis that increased heterogeneity of sympathetic innervation is related to the development of congestive heart failure. (5) The dual-modality imaging system will be used to measure the tumor and organ distribution of humanized anti-HER2 monoclonal antibody in a transgenic mouse model of metastatic breast cancer. The overall goal of this project wil1 develop a high-resolution imaging system that combines CT and SPECT to correlating structure and function. The system also will be designed to perform noninvasive serial studies in mice, and to replace invasive direct tissue sampling and autoradiography for biodistribution studies and functional assessments using radiolabeled tracers in transgenic mice.