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一种有前景的新几何结构的台式X射线荧光计算机断层扫描(XFCT)系统。这种新颖的几何结构包括对样品的铅笔束x射线照明，以及位置和能量敏感的荧光x射线探测器的狭缝准直。这允许直接 在不求解不适定问题的情况下获取照明线上的元素分布 反问题。虽然这项技术具有用于活体的潜力，但我们在这项提议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。许多内源金属和金属离子，如铁、铜、锌，在信号转导和反应催化中起着关键作用，而其他如汞、镉、铅等则具有很强的毒性，即使在微量情况下也是如此。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学科不断涌现，对内源金属进行系统研究。这些学科将从提议中探索的方法提供的微量元素分布和形态的空间分辨地图中受益匪浅。我们试图构建一种系统，能够以100微米的空间分辨率对亚厘米级的标本(如小鼠器官)进行成像，并具有合理的成像时间(~1-4小时)和低于损伤阈值的辐射剂量。该提案的具体目标是：目标1：将使用分析和基于蒙特卡洛的工具对系统设计进行灵敏度优化目标2：将制造台式XFCT系统目标3：将开发校准程序和成像算法目标4：将在模型和生物感兴趣的样本上测试该系统

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