X-Ray Fluorescence Computer Tomography with Emission Tomography Apertures

描述(由申请人提供)：这项建议的总体目标是开发和实施更快、更准确的基于同步加速器的X射线荧光计算机断层扫描(XFCT)方法，用于绘制生物样品中的痕量金属图。许多内源金属在信号转导和反应催化中起着关键作用，而另一些则具有很强的毒性，即使是微量的也是如此。这些金属在生物学上的研究将极大地受益于提议中探索的方法所提供的微量元素分布的三维空间分辨地图。此外，外源金属往往是新的体内分子显像剂的关键成分。这里提出的技术将提供校准和亚细胞定位信息，这对这些技术的继续进步至关重要。XFCT是一种受激发射层析成像(ET)方法，其中单色同步辐射X射线被用来激发样品的特征X射线发射，它具有在小而完整的样品中产生单个元素分布的三维地图的能力。目前，XFCT的主要局限性是其采集时间较长(每片约1小时或更多小时)，这限制了为了比较和改进实验统计而对多个样本进行成像的能力。这项拟议工作的关键动机是开发一种用于XFCT研究的新型检测系统，该系统具有极大的成像速度(速度快10到100倍)，同时保持合理的成像分辨率和对感兴趣的痕量元素的出色灵敏度。该提案的具体目标是：1.开发一种基于ET的XFCT应用检测系统。2.开发考虑二次和散射诱导的荧光并允许感兴趣区域成像的新的XFCT图像重建策略3.为了测试在生物学感兴趣的问题上开发的系统和算法：在完成后确定引入胰岛细胞中的锰的空间分布，该项目将提供一种在生物标本中以比目前可实现的显著更高的吞吐量进行痕量金属成像的有效手段。该项目还将为将该技术扩大到在动物和人类中进行体内微量金属成像奠定基础。 与公众健康相关：XFCT是一种受激发射断层扫描(ET)方法，其中使用单色同步加速器X射线来刺激样品中的特征X射线发射，它能够在一个小的、完整的样品中生成单个元素分布的三维地图。目前，XFCT的主要局限性是其采集时间较长(每片约1小时或更多小时)，这限制了为了比较和改进实验统计而对多个样本进行成像的能力。这项提议的总体目标是开发和实施更快、更准确的基于同步加速器的X射线荧光计算机层析成像(XFCT)方法，用于绘制生物样品中痕量金属的图谱。许多内源金属在信号转导和反应催化中起着关键作用，而另一些则具有很强的毒性，即使是微量的也是如此。这些金属在生物学上的研究将极大地受益于提议中探索的方法所提供的微量元素分布的三维空间分辨地图。此外，外源金属往往是新的体内分子显像剂的关键成分。这里提出的技术将提供校准和亚细胞定位信息，这对这些技术的继续进步至关重要。

DESCRIPTION (provided by applicant): The overall goal of this proposal is to develop and implement faster and more accurate synchrotron-based X-ray fluorescence computed tomography (XFCT) methods for the mapping of trace metals in biological samples. Many endogenous metals play critical roles in signal transduction and reaction catalysis, while others are quite toxic even in trace quantities. The study of these metals in biology would benefit greatly from the 3D spatially resolved maps of trace element distribution provided by the methods being explored in the proposal. In addition, exogenous metals are often critical components of new in-vivo molecular imaging agents. The techniques proposed here would provide calibration and subcellular localization information critical for the continued advancement of these technologies. XFCT is a stimulated emission tomography (ET) method in which monochromatic synchrotron X-rays are used to stimulate emission of characteristic X-rays from a sample, and it has the ability to produce three-dimensional maps of the distribution of individual elements in a small, intact specimen. As practiced now, the principal limitation of XFCT is its long acquisition time (on the order of 1 or more hours per slice), which limits the ability to image multiple samples for sake of comparison and improved experimental statistics. The key motivation for this proposed effort is to develop a novel detection system for XFCT studies that has a greatly improved imaging speed (10 to 100 times faster) while maintain a reasonable imaging resolution and an excellent sensitivity to the trace elements of interest. The specific aims of the proposal are: 1. To develop an ET-based detection system for XFCT applications. 2. To develop novel XFCT image reconstruction strategies accounting for secondary and scatter-induced fluorescence and that allow for region of interest imaging 3. To test the system and algorithms developed on a problem of biological interest: determining the spatial distribution of manganese introduced in islet cells Upon completion, this project will provide a validated means to perform trace metal imaging in biological specimens at significantly higher throughput than currently achievable. The project will also provide a foundation for scaling the techniques up to in vivo trace metal imaging in animals and humans. PUBLIC HEALTH RELEVANCE: XFCT is a stimulated emission tomography (ET) method in which monochromatic synchrotron X-rays are used to stimulate emission of characteristic X-rays from a sample, and it has the ability to produce three-dimensional maps of the distribution of individual elements in a small, intact specimen. As practiced now, the principal limitation of XFCT is its long acquisition time (on the order of 1 or more hours per slice), which limits the ability to image multiple samples for sake of comparison and improved experimental statistics. The overall goal of this proposal is to develop and implement faster and more accurate synchrotron-based X-ray fluorescence computed tomography (XFCT) methods for the mapping of trace metals in biological samples. Many endogenous metals play critical roles in signal transduction and reaction catalysis, while others are quite toxic even in trace quantities. The study of these metals in biology would benefit greatly from the 3D spatially resolved maps of trace element distribution provided by the methods being explored in the proposal. In addition, exogenous metals are often critical components of new in-vivo molecular imaging agents. The techniques proposed here would provide calibration and subcellular localization information critical for the continued advancement of these technologies.