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

散斑 X 射线成像：检测肺微结构的早期变化

• 批准号: 10560958
• 负责人: Peter B Noël
• 金额: $ 63.79万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10560958
• 关键词: Address; Affect; Alveolus; Animal Experimentation; Animal Experiments; Animal Model; Animals; Architecture; Area; Biological; Cancer Survivor; Clinical; Clinical Research; Darkness; Data; Dedications; Diagnostic X-Ray; Disease; Dose; Early Diagnosis; Electromagnetic Energy; Equipment; Evaluation; Gases; Goals; Image; Imaging Device; Individual; Interferometry; Investments; Laboratory Research; Lung; Lung diseases; Membrane; Methods; Modeling; Monitor; Mus; Optics; Outcome; Paper; Pattern; Performance; Phase; Photons; Physics; Proton Radiation; Pulmonary Fibrosis; Pulmonary alveolar structure; Radiation; Radiation Dose Unit; Radiation Toxicity; Radiation exposure; Radiation therapy; Research; Resolution; Roentgen Rays; Shapes; Shock; Signal Transduction; Site; Source; Structure; Synchrotrons; System; Techniques; Toxic effect; Translating; Translations; Treatment outcome; Treatment-related toxicity; United States; X-Ray Medical Imaging; attenuation; contrast imaging; cost; deep learning; design; detector; diagnostic accuracy; diagnostic tool; early onset; expiration; imaging detection; improved; in vivo; in vivo evaluation; longitudinal animal study; metallicity; microCT; nanoparticle; novel; particle; portability; pre-clinical; preclinical evaluation; preclinical imaging; preclinical study; prospective; proton therapy; prototype; public health relevance; research facility; side effect; software infrastructure; survivorship; targeted treatment; tool; transmission process; trend

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.

抽象的。 仅在美国，质子治疗中心的数量就增加到41个地点，还有更多 目前正在建设或计划阶段。虽然此类中心的投资是数百个 数以百万计的美元，正在进行研究以确定质子治疗是否改善治疗结果。 在该活跃研究领域评估肺泡体系结构的敏感诊断工具不仅将 使早期的靶向治疗减慢辐射引起的肺纤维化的进展，但也 显着受益于正在进行的临床前评估。目前正在使用的成像工具很差 中等灵敏度不足以检测肺的早期变化和/或证明是不切实际的 关于纵向临床前研究的辐射剂量和后勤复杂性。解决这个关键 需要，我们引入了一种成像工具，用于通过推进肺微观结构变化的早期检测 X射线Darkfield成像的新兴领域。在常规X射线中，图像对比是通过衰减形成的 关于将X射线作为颗粒的解释。如果将X射线视为电磁波，则附加X射线对比度 可以访问衍射，相移和小角度散射等机制。 X射线散射 健康，充气肺肺泡会产生强烈的黑场信号，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了 平均十周 - 练习率检测到辐射引起的肺纤维化的早期发作 常规光子疗法。已经研究了许多获取X射线黑场图像的方法 最近几年。但是，当前的解决方案需要复杂的，令人震惊且昂贵的硬件 实施。一种更实用的方法涉及使用由随机结构组成的过滤器（所谓的 扩散器）生成近场干扰斑点图案，用于获取黑场图像。我们的长期 目标是将物理研究实验室的X射线暗场成像转换为临床前成像领域 为纵向肺部评估提供所需的工具。我们的解决方案包括新颖的深层设计 基于学习的斑点跟踪与基于纳米颗粒的扩散器设计结合 与光栅相比，制造便宜。将追求以下具体目标：（1）开发一个 用于体内小动物X射线黑暗菲尔德成像的软件基础架构，（2）实现X射线Darkfield 用于检测放射疗法早期肺毒性的原型，以及（3）评估X射线darkfield原型 幻影和体内纵向动物研究的表现。该建议将推进Speckle-的领域 基于X射线暗场成像通过加深基本的理解并通过物理学转化它 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。提议 解决方案有可能将X射线暗场成像转移到临床常规中的转换。