Development of a benchtop x-ray fluorescence tomography system using a novel geom

描述（由申请人提供）：本提案的目标是构建、优化和测试基于我们最近开发并使用同步辐射验证的有前途的新几何结构的台式X射线荧光计算机断层扫描（XFCT）系统。新的几何形状涉及的位置和能量敏感的荧光X射线检测器的狭缝准直耦合的样品的双光束X射线照明。这使得直接 获取元素沿着照明线的分布，而不解决不适定 逆问题虽然该技术有可能在体内使用，但我们在该提案中的目标是对生物样品中的痕量金属进行非常高质量的体外成像。 许多内源性金属和金属离子，如铁、铜和锌，在信号传导和反应催化中起着关键作用，而其他的，如汞、镉和铅，即使是微量的，也是相当有毒的。在后基因组时代，金属基因组学、金属蛋白质组学和金属组学等新兴学科的出现，为内源性金属的系统研究提供了新的思路。这些学科将大大受益于该提案中正在探讨的方法所提供的空间分辨的微量元素分布和形态形成图。 我们试图构建一个系统，可以成像亚厘米标本（如小鼠器官）在100微米的空间分辨率，合理的成像时间（约1-4小时）和辐射剂量低于损伤阈值。该提案的具体目标是：目标1：将使用分析和基于蒙特卡罗的工具优化系统设计的灵敏度目标2：将制造台式XFCT系统目标3：将开发校准程序和图像形成算法目标4：将在体模和生物感兴趣的样品上测试系统

DESCRIPTION (provided by applicant): The goal of this proposal is to construct, optimize, and test a bench top x-ray fluorescence computed tomography (XFCT) system based on a promising new geometry we have recently developed and validated using synchrotron radiation. The novel geometry involves pencil-beam x-ray illumination of the sample coupled with slit collimation of a position- and energy-sensitive fluorescence x-ray detector. This allows for direct acquisition of the distribution of elements along the illuminated line without solving an ill-posed inverse problem. While the technology has the potential to be used in vivo, our aim in this proposal is to perform very high quality ex-vivo imaging of trace metals in biological samples. Many endogenous metals and metal ions, such as iron, copper, and zinc, play critical roles in signal transduction and reaction catalysis, while others, such as mercury, cadmium, and lead, are quite toxic even in trace quantities. In the post-genomic era, the new disciplines of metallogenomics, metalloproteomics, and metallomics are emerging for the systematic study of endogenous metals. These disciplines would benefit greatly from the spatially resolved maps of trace-element distribution and speciation provided by the methods being explored in the proposal. We seek to construct a system that can image sub-centimeter specimens (such as mouse organs) at 100 micron spatial resolution, with reasonable imaging times (~ 1-4 hours) and at radiation doses below damage threshold. The specific aims of the proposal are: Aim 1: The system design will be optimized for sensitivity using analytic and Monte Carlo-based tools Aim 2: A benchtop XFCT system will be fabricated Aim 3: Calibration procedures and image formation algorithms will be developed Aim 4: The system will be tested on phantoms and samples of biological interest