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

项目摘要 在这个项目中，我们提出了开发和优化一种新型的x射线荧光发射层析成像系统 生物样品中痕量金的图像重建算法。金纳米颗粒(GNPs)发挥着 在癌症治疗中的重要作用，在金属沉思放射治疗中作为放射增敏剂和关键 用于光热消融治疗的组件。这些疗法为浅表皮损提供了一种很有希望的治疗方法。 目前正在进行体内和临床试验，但可能会看到疗效的改善和副作用的减少 如果能够准确地绘制出GNPs的位置和浓度，将会产生怎样的影响。然而，目前的金属测绘 方法不能提供成像相关金属所需的灵敏度或组织穿透深度 浓度。要将这些疗法转移到临床上，需要有一种高度敏感的金属- 测绘成像模式，可以对相关浓度和深度的黄金进行成像。 近年来，X射线荧光层析成像已成为一种很有前途的金属标绘方法。 具体地说，X射线荧光发射断层成像(XFET)提供了成像痕迹所需的高灵敏度 用于体内和临床研究的金。此外，xFET还具有其他x射线荧光无法比拟的优点。 成像方式：它提供金属的直接测量，而不会放大断层扫描图像的噪声 重建，而且不需要完整的正弦图，这限制了其他组织的穿透深度 医疗模式。在拟议的工作中，我们将优化现有XFET的硬件捕获参数 系统以最大限度地提高黄金的可探测性。我们还将优化XFET图像重建算法，以联合 估计金属贴图和衰减贴图，提供了一种获得衰减贴图的新方法 否则，这将通过额外的剂量递送计算机断层扫描(CT)获得。 该建议的具体目标是：1)开发算法和现实的正演模型，以联合 重建物体的金属分布和衰减图，2)优化XFET硬件采集 在指定的辐射剂量水平下最大化金的可探测性的参数，以及3)验证重建 在小鼠模型中的方法和优化策略，评估最小可检测到的金浓度， 并将图像质量指标与CT进行比较。完成后，目标1将提供一种在低点绘制金属地图的方法 以及一种使用荧光发射数据获得衰减图的新方法。目标2将 设计了一种新颖的系统几何结构，其参数可最大限度地提高黄金的可探测性。AIM 3将演示XFET 对图像质量指标进行灵敏度限制，并与现有系统进行比较。这些结果将使我们能够 对这个临床前系统在最终临床场景中的能力的预测，为XFET铺平了道路 用作临床成像系统，能够绘制治疗性GNPs图，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.