X-ray fluorescence emission tomography for imaging trace gold in mouse models

项目摘要 在本计画中，我们提出发展及最佳化一种新颖的X射线萤光发射断层摄影系统 和重建算法来成像生物样品中的痕量金。金纳米颗粒（GNP）在 在癌症治疗中起重要作用，在金属介导的放射治疗中作为放射增敏剂， 光热消融治疗的组成部分。这些疗法为浅表病变提供了有希望的治疗方法 目前正在体内和临床试验中探索，但可以看到改善的疗效和减少的副作用， 如果能够准确绘制GNP的位置和浓度，将产生影响。然而，目前的金属映射 方法不提供对相关金属成像所需的灵敏度或组织穿透深度 浓度的为了将这些疗法应用于临床，需要一种高度敏感的金属- 映射成像模态，其可以在相关浓度和深度处对金进行成像。 近年来，X射线荧光断层扫描已成为一种很有前途的模式，金属映射。 特别是，X射线荧光发射断层扫描（XFET）提供了成像跟踪所需的高灵敏度 用于体内和临床研究的金。此外，XFET提供优于其他X射线荧光的优点 成像方式：它提供了一个直接测量的金属没有噪声放大断层图像 这是一种简单的重建方法，并且它不需要完整的正弦图，这限制了其他重建方法的组织穿透深度。 方式。在所提出的工作中，我们将优化现有XFET的硬件采集参数 最大限度地提高黄金探测能力。我们还将优化XFET图像重建算法， 估计金属图以及衰减图，提供了一种用于获得衰减图的新方法 否则将通过附加的剂量递送计算机断层摄影（CT）扫描获得。 该建议的具体目标是：1）开发算法和现实的正演模型， 重建目标的金属分布和衰减图，2）优化XFET硬件采集 参数，以最大限度地提高在指定的辐射剂量水平的黄金可探测性，和3）验证重建 方法和优化策略，评估最小可检测金浓度， 并将图像质量指标与CT进行比较。完成后，目标1将提供一种方法， 浓度，以及使用荧光发射数据获得衰减图的新方法。目标2将 设计一种新颖的系统几何形状，其参数使黄金的可探测性最大化。Aim 3将展示XFET 灵敏度限制，并将图像质量指标与现有系统进行比较。这些结果将使我们能够 预测这种临床前系统在最终临床场景中的能力，为XFET铺平道路 作为临床成像系统，能够映射治疗性GNP，以实现更安全的治疗和更少的副作用， 在癌症治疗中的作用

Project Summary In this project, we propose to develop and optimize a novel X-ray fluorescence emission tomography system and reconstruction algorithm to image trace gold in biological samples. Gold nanoparticles (GNPs) play an important role in cancer therapy, serving as radiosensitizers in metal-meditated radiation therapy and as critical components to photothermal ablation therapy. These therapies offer a promising treatment for superficial lesions and are currently being explored in in vivo and clinical trials, but could see improved efficacy and decreased side effects if the location and concentrations of GNPs could be mapped accurately. However current metal-mapping methods do not provide the sensitivity or tissue penetration depth necessary to image relevant metal concentrations. For these therapies to be translated to the clinic, there needs to be a highly sensitive metal- mapping imaging modality that can image gold at the relevant concentrations and depths. In recent years, X-ray fluorescence tomography has emerged as a promising modality for metal-mapping. Specifically, X-ray fluorescence emission tomography (XFET) offers high sensitivity needed for imaging trace gold used in in vivo and clinical studies. Furthermore, XFET offers advantages over other x-ray fluorescence imaging modalities: it provides a direct measurement of the metal without noise-amplifying tomographic image reconstruction, and it does not require a full sinogram, which limits the tissue penetration depth of other modalities. In the proposed work, we will optimize the hardware acquisition parameters of an existing XFET system to maximize gold detectability. We will also optimize an XFET image reconstruction algorithm to jointly estimate metal maps as well as attenuation maps, providing a novel method for obtaining an attenuation map that would otherwise be obtained by an additional, dose-delivering computed tomography (CT) scan. The specific aims of this proposal are: 1) develop algorithms and a realistic forward model to jointly reconstruct metal distributions and attenuation maps of objects, 2) optimize XFET hardware acquisition parameters to maximize gold detectability at specified radiation dose levels, and 3) validate reconstruction methods and optimization strategies in mouse phantom models, assess minimum detectable gold concentration, and compare image quality metrics to CT. Upon completion, aim 1 will provide a method to map metals at low concentrations, and a novel method of obtaining an attenuation map using fluorescent emission data. Aim 2 will design a novel system geometry with parameters that maximize gold detectability. Aim 3 will demonstrate XFET sensitivity limits and compare image quality metrics to an existing system. These results will allow us to make predictions about this preclinical system’s capabilities in an eventual clinical scenario, paving the way for XFET to be used as a clinical imaging system capable of mapping therapeutic GNPs for safer treatment and fewer side effects in cancer therapies.