Speckle x-ray imaging: detecting early changes in lung microstructure

抽象的。 仅在美国，质子治疗中心的数量就增加到了41个，还有更多 目前正在建设或处于规划阶段。虽然这类中心的投资高达数百美元 耗资数百万美元的研究正在进行中，以确定质子疗法是否会改善治疗结果。 在这一活跃的研究领域，评估肺泡结构的敏感诊断工具不仅将 使早期靶向治疗能够减缓放射性肺纤维化的进展，但也 显著受益于正在进行的临床前评估。目前使用的成像工具有一个很差的 中等敏感度，不足以检测肺部早期变化和/或被证明是不切实际的 关于辐射剂量和纵向临床前研究的后勤复杂性。要解决这一关键问题 需要，我们介绍了一种成像工具，以早期检测肺微结构的变化，通过推进 X射线暗场成像的新兴领域。在传统的x射线中，图像对比度是通过衰减形成的 关于x射线作为粒子的解释。如果将X射线感测为电磁波，则额外的X射线对比度 可以访问诸如衍射、相移和小角散射等机制。X射线散射打开 健康、充气的肺泡会产生强烈的暗场信号，当 肺泡的完整性受到影响。初步的体内小动物实验成功证明 一项平均提前10周发现放射性肺纤维化早期发病的研究 传统的光子疗法。已经研究了许多获取x射线暗场图像的方法。 在最近几年。然而，目前的解决方案需要复杂、对冲击敏感且昂贵的硬件 实施。一种更实用的方法涉及使用由随机结构(所谓的 漫射器)以产生近场干涉散斑图案以获取暗场图像。我们的长期合作 目标是将x射线暗视野成像从物理研究实验室转移到临床前成像领域。 为纵向肺评估提供必要的工具。我们的解决方案包括设计新颖的深度- 基于学习的斑点跟踪与基于纳米颗粒的漫射器设计相结合 与栅格相比，制作成本更低。具体目标如下：(1)发展 用于体内小动物x射线暗场成像的软件基础设施，(2)实现x射线暗场 用于检测放射治疗早期肺毒性的原型，以及(3)评估x射线暗场原型 在幻影和体内纵向动物研究中的表现。这项提议将推进散斑领域- 通过加深对X射线暗场成像的基本理解并将其从物理上转化为基础 研究实验室进入临床前领域。为此，我们预计我们的x射线暗场 成像概念将作为纵向体内小动物研究的低剂量工具。建议数 解决方案有可能推动X射线暗视野成像向前转化为临床常规。

Abstract. In the United States alone, the number of proton therapy centers has increased to 41 sites, with many more currently under construction or in planning stage. While the investment for such centers is in the hundreds of millions of US dollars, research is ongoing to determine whether proton therapy improves treatment outcomes. A sensitive diagnostic tool for the evaluation of alveoli architecture in this active research area would not only enable early targeted treatment to slow down progression of radiation-induced lung fibrosis but also significantly benefit the ongoing preclinical evaluation. The imaging tools currently in use have a poor to moderate sensitivity that is insufficient for detecting early changes in the lungs and/or are proving impractical with respect to radiation dose and logistical complexity for longitudinal preclinical studies. To address this critical need, we introduce an imaging tool for early detection of lung microstructural changes by advancing the emerging field of x-ray darkfield imaging. In conventional x-ray, image contrast is formed by attenuation based on the interpretation of x-rays as particles. If sensing x-rays as electromagnetic waves, additional x-ray contrast mechanisms such as diffraction, phase-shift and small-angle scattering can be accessed. X-ray scattering on healthy, gas-filled pulmonary alveoli generates a strong darkfield signal, and the signal decreases when the integrity of the alveoli is affected. Preliminary in-vivo small animal experiments successfully demonstrated an on average ten-weeks-earlier detection of early onset of radiation-induced lung fibrosis from conventional photon therapy. A number of methods for acquiring x-ray darkfield images have been investigated in recent years. However, current solutions require complicated, shock-sensitive and expensive hardware implementations. A more practical method involves the use of filters consisting of random structures (so-called diffusers) to generate near-field interference speckle patterns for acquiring darkfield images. Our long-term goal is translating x-ray dark-field imaging from physics research laboratories into the preclinical imaging arena to provide the needed tool for longitudinal lung assessment. Our solution includes the design of novel deep- learning based speckle tracking in combination with a diffuser design based on nanoparticles which is inexpensive to fabricate compared to gratings. The following specific aims will be pursued: (1) to develop a software infrastructure for in-vivo small animal x-ray darkfield imaging, (2) to implement an x-ray darkfield prototype for detection of early pulmonary toxicity from radiotherapy, and (3) to evaluate x-ray darkfield prototype performance in phantoms and in-vivo longitudinal animal studies. This proposal will advance the field of speckle- based x-ray dark-field imaging by deepening the basic understanding and by translating it from physics research laboratories into the preclinical arena. Toward this end, we anticipate that our x-ray dark-field imaging concept will serve as a low-dose tool for longitudinal in-vivo small animal studies. The proposed solutions have the potential to drive the translation of x-ray dark-field imaging forward into the clinical routine.