CT SYSTEM FOR THE STUDY OF BIOLOGICAL STRUCTURE

本研究的总体目标是响应（PAR-97-074）“创新 开发新技术的方法”，就是开发潜力， 小规模计算机断层扫描（CT）的横截面成像 小型啮齿动物模型。 实验室小鼠和大鼠是关键 参与医学研究的领域包括致癌作用， 药物开发，心血管疾病，艾滋病研究， 设备测试等。商用CT扫描仪的分辨率 人类成像是在500 μ m的量级上，并且该分辨率也是 由于小鼠或大鼠的体积小， 这些动物的体型。 因此，为了研究变化 在这些研究动物中，通常需要牺牲它们， 进行直接解剖可视化（例如厚切片显微镜检查）。 在许多研究中，动物队列受到一些研究 然后在不同的时间点， 并在死后研究它们的解剖结构。 长 这项技术开发提案的长期目标是开发一种 专门设计用于产生高分辨率（例如，50至 100 μ m像素）的适当约束的横截面图像， 麻醉的小型啮齿动物体内具体目标是：（1）设计 并搭建CT硬件;（2）设计、编写和测试所需的 软件控制旋转和数据采集，（3）使用 理论和计算机模拟方法，开发和优化CT 重建算法适合于特定的几何形状的小 扫描仪，最后（4）测量CT的成像性能 扫描仪 同步辐射源的注量率比x射线大得多 荧光镜系统，但它们并不广泛使用，而且也很普遍 为了这个目的是昂贵的。 拟设系统可 利用来自通用荧光透视系统的X射线， 特别设计为易于适应大多数荧光透视X射线 管，这是广泛适用于任何医疗中心。微型CT 系统目前在PI的实验室运行，该实验室采用 50 μ m像素，并且具有每mm 10个周期的极限空间分辨率。 该系统可生成高对比度物体的出色图像， 然而，骨骼的结构从根本上局限于 由于信号而对动物内的软组织结构进行成像的能力 噪音限制。 SNR限制由有限的x- 所用透视X射线系统的射线输出。 在本提案中，我们 我希望通过建立一个系统来扩展微型CT系统的性能 其能够使用高得多的X射线注量率， 更靠近X射线焦点。例如，通过移动 探测器从其当前位置距源51 cm到10 cm远， X射线注量率可以增加26倍（平方反比定律）， 将理论SNR提高5倍（SNR约为DOSE 1/2）。 然而，通过将探测器移动到如此靠近X射线源， 它的物理尺寸成为实现空间的主要障碍， 分辨率提出了技术（多步反卷积）以 补偿图像重建中的这种“焦点模糊 过程 本提案的重点是研究各种CT扫描仪 设计，特别注意产生一个实际的解决方案， 成像小动物;这样的系统将有可能 对生物医学研究的广泛影响。 此外，由于能够 研究单个动物体内的解剖学变化， 将使研究人员有可能大幅减少 同时获得更高的统计功效， 由于个体的生物结构可以连续地监测， 时间，个体之间对治疗的反应的变化 研究中被淘汰。

The overall goal of this study, in response to (PAR-97-074) "Innovative approaches to developing new technologies", is to develop the potential of a small scale computed tomography (CT) for cross-sectional imaging of small rodent models. The laboratory mouse and rat are key participants in medical research in areas including carcinogenesis, pharmaceutical development, cardiovascular disease, AIDS research, device testing, and so on. The resolution of commercial CT scanners for human imaging is on the order of 500 mum, and this resolution is too poor to properly image the anatomy of a mouse or a rat, due to the small physical dimensions of these animals. Consequently, to study changes in these research animals, it often is necessary to sacrifice them and perform direct anatomical visualization (e.g. thick section microscopy). In many studies, cohorts of animals are subjected to some research regiment, and then at various time points, some fraction of the cohort is sacrificed and their anatomies are studied post mortem. The long term objective of this technology-development proposal is to develop a CT scanner specifically designed to produce high resolution (e.g. 50 to 100 mum pixels) cross-sectional images of suitably restrained and anethesized small rodents, in vivo. The specific aims are to: (1) design and build the CT hardware, (2) design, write and test the necessary software to control the rotation and data acquisition, (3) using theoretical and computer simulation methods, develop and optimize a CT reconstruction algorithm tailored to the specific geometry of the small scanner, and finally (4) to measure the imaging performance of the CT scanner. Synchrotron sources have much greater fluence rates than x-ray fluoroscopic systems, however they are not widely available and are too expensive to be practical for this purpose. The proposed system will make use of x-rays from a general purpose fluoroscopic system, and will be specifically designed to adapt easily to most fluoroscopic x-ray tubes, which are widely available in any medical center. A micro-CT system is currently operational in the PI's laboratory, which employs 50 mum pixels and has a limiting spatial resolution of 10 cycles per mm. This system produces excellent images of high contrast objects such as the structure of bone, however is it fundamentally limited in its ability to image soft tissue structure within an animal due to signal to noise limitation. The SNR limitations are imposed by the limited x- ray output of the fluoroscopic x-ray system used. In this proposal, we hope to extend the performance of micro-CT systems by building a system which is capable of using the much higher x-ray fluence rates which exist closer to the x-ray focal spot. For example, by moving the detector from its current location 51 cm from the source to 10 cm away, the x-ray fluence rate can be increased 26 fold (inverse square law), improving the theoretical SNR by a factor of 5 (SNR approximately DOSE 1/2). However, by moving the detector so close to the x-ray source, it's physical size becomes a major detriment to achieving spatial resolution. Techniques are proposed (multi-step deconvolution) to compensate for this "focal spot blurring" in the image reconstruction process. The focus of this proposal is to study various CT scanner designs with specific attention to producing a practical solution to imaging small animals; as such a system will have the potential for broad impact on biomedical research. Furthermore, with the ability to study anatomical changes within a single animal, the proposed scanner will make it possible for researchers to substantially reduce the number of animals used and simultaneously achieve higher statistical power, since the bio-structure of individuals can be monitored serially over time, the variation in response between individuals to the treatment under study is eliminated.