X-Ray Fluorescence Computer Tomography with Emission Tomography Apertures

描述（由申请人提供）：本提案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。许多内源性金属在信号传导和反应催化中起着关键作用，而另一些即使在微量也具有相当的毒性。生物学中这些金属的研究将极大地受益于该提案中探索的方法提供的微量元素分布的3D空间分辨率地图。此外，外源性金属通常是新的体内分子成像剂的关键组分。这里提出的技术将提供校准和亚细胞定位信息，这些技术的持续发展至关重要。 XFCT是一种受激发射断层扫描（ET）方法，其中单色同步加速器X射线用于激发样品中特征X射线的发射，并且它能够在小的完整样品中产生单个元素分布的三维图。如现在所实践的，XFCT的主要限制是其长的采集时间（每个切片大约1小时或更长时间），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。 这项工作的主要动机是开发一种用于XFCT研究的新型检测系统，该系统具有大大提高的成像速度（快10至100倍），同时保持合理的成像分辨率和对感兴趣的微量元素的出色灵敏度。该提案的具体目标是：1。为XFCT应用开发基于ET的检测系统。2.开发新的XFCT图像重建策略，考虑二次和散射诱导荧光，并允许感兴趣区域成像3。为了测试开发的系统和算法上的一个问题的生物利益：确定锰的空间分布引入胰岛细胞完成后，该项目将提供一个验证的手段，以执行微量金属成像在生物标本中显着更高的吞吐量比目前可实现的。该项目还将为将这些技术扩展到动物和人类的体内痕量金属成像提供基础。 公共卫生相关性：XFCT是一种受激发射断层扫描（ET）方法，其中单色同步加速器X射线用于激发样品中特征X射线的发射，并且它能够在小的完整样品中产生单个元素分布的三维图。如现在所实践的，XFCT的主要限制是其长的采集时间（每个切片大约1小时或更长时间），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。该提案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。许多内源性金属在信号传导和反应催化中起着关键作用，而另一些即使在微量也具有相当的毒性。生物学中这些金属的研究将极大地受益于该提案中探索的方法提供的微量元素分布的3D空间分辨率地图。此外，外源性金属通常是新的体内分子成像剂的关键组分。这里提出的技术将提供校准和亚细胞定位信息，这些技术的持续发展至关重要。

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.