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

X 射线荧光发射断层扫描用于对小鼠模型中的痕量金进行成像

• 批准号: 10537866
• 负责人: Hadley Anna DeBrosse
• 金额: $ 4.77万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-06 至 2026-01-05
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10537866
• 关键词: Ablation; Algorithms; Animal Model; Biological; Brain; Clinic; Clinical; Clinical Research; Clinical Trials; Data; Dose; Drug Delivery Systems; Elements; Failure; Fluorescence; Geometry; Goals; Gold; Human body; Illinois; Image; In Vitro; Investigation; Joint repair; Location; Malignant Neoplasms; Maps; Measurement; Measures; Mediating; Meditation; Metals; Methods; Modality; Modeling; Monitor; Monte Carlo Method; Mus; Noise; Organism; Penetration; Play; Positioning Attribute; Property; Radiation Dose Unit; Radiation therapy; Radiation-Sensitizing Agents; Radioactivity; Radiosensitization; Research; Resolution; Roentgen Rays; Role; Sampling; Scanning; Spatial Distribution; Specific qualifier value; Superficial Lesion; System; Techniques; Therapeutic; Thermal Ablation Therapy; Time; Tissues; Translating; Universities; Work; X-Ray Computed Tomography; X-Ray Medical Imaging; attenuation; cancer care; cancer therapy; clinical imaging; density; design; detector; fluorescence imaging; image reconstruction; imaging modality; imaging system; improved; in vivo; mouse model; nanoGold; novel; particle; phantom model; pre-clinical; reconstruction; side effect; tomography; transmission process; tumor

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.

项目摘要 在这个项目中，我们建议开发和优化一种新型的X射线荧光发射断层扫描系统 和重建算法以在生物样品中图像痕量金。金纳米颗粒（GNP）玩 在癌症疗法中的重要作用，作为金属成熟的放射疗法的放射增敏剂，至关重要 光热消融疗法的成分。这些疗法为表面腿提供了承诺治疗 目前正在体内和临床试验中进行探索，但可以提高效率和提高的一面 如果可以准确地映射GNP的位置和浓度，效果。但是当前的金属映射 方法不提供图像相关金属所需的灵敏度或组织穿透深度 浓度。要将这些疗法转化为诊所，需要有高度敏感的金属 映射成像方式，可以在相关浓度和深度上成像金。 近年来，X射线荧光断层扫描已成为金属映射的希望形式。 具体而言，X射线荧光发射断层扫描（XFET）具有成像迹象所需的高灵敏度 黄金用于体内和临床研究。此外，XFET提供了比其他X射线荧光的优点 成像方式：它可以直接测量金属，而无需扩大噪声层析成像图像 重建，并且不需要完整的辛克图，这限制了其他的组织渗透深度 方式。在拟议的工作中，我们将优化现有XFET的硬件采集参数 系统以最大化黄金可检测性。我们还将优化XFET图像重建算法与共同 估计金属图和衰减图，提供了一种新的方法来获得衰减图 否则，这将通过额外的剂量分配计算机断层扫描（CT）扫描获得。 该提案的具体目的是：1）开发算法和一个现实的远期模型 重建金属分配和对象的衰减图，2）优化XFET硬件获取 在指定的辐射剂量水平上最大化黄金可检测性的参数，3）验证重建 小鼠幻像模型中的方法和优化策略，评估最低可检测的金浓度， 并将图像质量指标与CT进行比较。完成后，AIM 1将提供一种方法来绘制低点的金属 浓度和一种使用荧光发射数据获得衰减图的新方法。 AIM 2意志 设计一种具有最大化金可检测性的参数的新型系统几何形状。 AIM 3将演示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 在最终的临床情况下，有关此临床前系统功能的预测，为XFET铺平了道路 用作能够绘制治疗GNP的临床成像系统，以进行安全治疗，较少的一面 在癌症疗法中的影响。