Towards in vivo imaging with benchtop x-ray fluorescence computed tomography

 描述（由申请人提供）：通过最近对金纳米颗粒（GNP）的一系列研究，目前的研究团队已经表明，X射线荧光计算机断层扫描（XFCT），传统上是一种基于同步加速器的成像方式，可以使用普通诊断能量范围多色X射线源在小型动物大小的物体的台式设置上进行。因此，现在可以设想XFCT在生物医学研究中的广泛使用，特别是鉴于对高原子序数（Z > ~50）金属纳米颗粒如GNP用于各种癌症诊断/治疗应用以及使用小动物模型对这些应用进行临床前测试的兴趣不断增长。一旦完全开发，台式XFCT将提供一个强大的工具来确定GNP和其他金属NP探针在体内的生物分布，而无需在处死动物后进行繁琐和耗时的离体分析。此外，它将在单个平台中实现micro-CT（µCT）的无缝多模式成像，从而使图像显示更多的解剖细节，同时保留光谱定量成像的所有优势。此外，当使用生物缀合/官能化GNP和/或其他金属NP探针进行时，台式µCT/XFCT将为更有效的药物发现和开发提供前所未有的多模式/多重分子成像选择。尽管近年来台式XFCT的研究取得了重大进展，但要实现这些可能性，必须克服一些关键的技术挑战。因此，该项目汇集了来自布鲁克海文国家实验室、马萨诸塞州大学医学院和德克萨斯大学MD安德森癌症中心的专家团队，以克服阻碍设想的台式µCT/XFCT系统在现实限制下常规用于体内成像的关键技术障碍。为实现该项目的目标，将努力实现以下三个具体目标： (1)台式µCT/XFCT系统的设计和优化;（2）用于台式XFCT的新型高能量分辨率固态阵列探测器的开发;（3）台式µCT/XFCT系统的多模式/多路分子成像能力的研究。成功完成后，实用的台式µCT/XFCT系统将为常规临床前分子成像研究和进一步改进做好准备。一个完全开发的台式µCT/XFCT系统将提供新的成像选择，可以大大提高基于NP的诊断/治疗策略的临床前测试的有效性，从而增加在癌症纳米医学中带来范式转移进步的可能性。该项目开发的新型高能量分辨率探测器系统也将为台式XFCT之外的广泛定量X射线成像应用提供新的机会。

 DESCRIPTION (provided by applicant): Through a series of recent studies with gold nanoparticles (GNPs), the current research team has shown that x-ray fluorescence computed tomography (XFCT), traditionally a synchrotron-based imaging modality, can be performed on a benchtop setting for small-animal-sized objects using an ordinary diagnostic energy range polychromatic x-ray source. Consequently, one can now envision a widespread use of XFCT for biomedical research, especially in light of ever-growing interest in high atomic number (Z > ~50) metal nanoparticles such as GNPs for various cancer diagnostic/therapeutic applications and preclinical testing of such applications using small animal models. Once fully developed, benchtop XFCT will offer a powerful tool to determine the biodistribution of GNPs and other metal NP probes in vivo without cumbersome and time-consuming ex vivo analysis after sacrificing animals. Moreover, it will enable seamless multimodal imaging with micro-CT (µCT) in a single platform, resulting in images showing greater anatomical details while retaining all the benefits from spectroscopic quantitative imaging. Furthermore, when performed with bioconjugated/functionalized GNPs and/or other metal NP probes, benchtop µCT/XFCT will provide an unprecedented multimodal/multiplexed molecular imaging option for more effective drug discovery and development. Despite significant research advances on benchtop XFCT in recent years, however, there are some critical technical challenges that must be overcome to realize these possibilities. Thus, this project brings together a team of experts from Brookhaven National Laboratory, University of Massachusetts Medical School, and The University of Texas MD Anderson Cancer Center to surmount the key technical hurdles that prevent the envisioned benchtop µCT/XFCT system from being used routinely for in vivo imaging under realistic constraints. The following three specific aims will be pursued to achieve the goal of this project: (1) Design and optimization of a benchtop µCT/XFCT system; (2) Development of novel high energy-resolution solid state array detectors for benchtop XFCT; (3) Investigation of multimodal/multiplexed molecular imaging capability of a benchtop µCT/XFCT system. Upon successful completion, a practical benchtop µCT/XFCT system will become ready for routine preclinical molecular imaging studies and further improvements. A fully-developed benchtop µCT/XFCT system will offer novel imaging options that can considerably improve the efficacy of preclinical testing of NP- based diagnostic/therapeutic strategies, thereby increasing the likelihood of bringing paradigm-shifting advancements in cancer nanomedicine. A novel high energy-resolution detector system developed from this project will also offer new opportunities for a wide range of quantitative x-ray imaging applications beyond benchtop XFCT.