Development of a Quantitative Iron Characterization System for Alzheimer's Disease Using Computed Laminography X-ray Fluorescence Imaging (CL-XRFI)

使用计算机断层扫描 X 射线荧光成像 (CL-XRFI) 开发阿尔茨海默氏病的定量铁表征系统

• 批准号: 10306411
• 负责人: Wenbing Yun
• 金额: $ 79.52万
• 依托单位: SIGRAY, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10306411
• 关键词: Ablation; Alzheimer' s Disease; Amyloid beta-Protein; Anodes; Biological; Brain; Brain region; Cellular Structures; Cessation of life; Data Collection; Detection; Development; Drug Design; Drug Targeting; Effectiveness; Elements; Ensure; Event; Excision; Feedback; Fluorescence; Goals; Hour; Image; Incidence; Inductively Coupled Plasma Mass Spectrometry; Information Distribution; Iron; Iron Chelating Agents; Laboratories; Lasers; Legal patent; Letters; Link; Measures; Metals; Methods; Microscopy; Microtomy; Nerve Degeneration; Neurodegenerative Disorders; Optics; Parkinson Disease; Pathologic; Pathway interactions; Performance; Pharmaceutical Preparations; Phase; Preparation; Property; Research; Resolution; Roentgen Rays; Rotation; Sampling; Scanning; Scheme; Signal Transduction; Slice; Solid; Source; Specimen; Speed; Surface; Synchrotrons; System; Techniques; Technology; Time; Trace Elements; Work; absorption; base; brain tissue; commercialization; design; detection sensitivity; detector; fluorescence imaging; imaging system; improved; innovation; novel; novel therapeutics; phantom model; prevent; prototype; reconstruction; success; targeted treatment; theories; therapeutic development; therapeutic target

The discovery of ferroptosis has invigorated new therapeutics to prevent and/or alter pathological iron distribution in the brain correlated with Alzheimer’s disease (AD) and other neurodegenerative diseases. To efficiently evaluate new drug designs, techniques capable of directly imaging and quantifying the trace levels of iron in brain samples are required. Current approaches include LA-ICPMS and synchrotron microXRF, which each have their own drawbacks in terms of speed, quantification reliability, and accessibility. We propose to develop a scheme called computed laminography x-ray fluorescence imaging (CL-XRFI). In this novel system design, an x-ray beam is focused into a pencil-like beam incident upon a sample at a very low angle (3 degrees). A detector is placed parallel to the sample surface to maximize solid angle. Acquisition is similar in concept to absorption-based laminography, in which acquisition at multiple angles are taken for reconstruction of the signal origin. The system design is uniquely enabled by the company’s patented high brightness x-ray source and its proprietary x-ray optic technology that provides the large working distances necessary for the technique to work. The proposed Phase I 6-month project is a proof-of-principle demonstration of the sensitivity and throughput of a breadboard low angle incidence fluorescence system. The proposed Phase II 24-month project is to develop a complete prototype of the CL-XRFI.

铁性下垂的发现激发了预防和/或改变的新疗法 脑内病理性铁的分布与阿尔茨海默病(AD)和其他 神经退行性疾病。为了有效地评估新药设计，能够 直接成像和量化大脑样本中的微量铁水平是必要的。当前 方法包括LA-ICPMS和同步加速器MicroXRF，它们都有自己的方法 在速度、量化可靠性和可访问性方面存在缺陷。 我们建议开发一种称为计算机层析x射线荧光成像的方案。 (CL-XRFI)。在这种新颖的系统设计中，x射线束被聚焦成铅笔状的光束。 以非常小的角度(3度)入射到样品上。探测器被放置在与 样本表面，以最大限度地提高立体角度。收购在概念上类似于基于吸收的收购 层析成像技术，采用多角度采集以重建信号 起源。该系统的设计是由该公司专利的高亮度X射线独一无二的 光源及其专有的X射线光学技术提供了大的工作距离 是这项技术发挥作用所必需的。 拟议的为期6个月的第一阶段项目是对敏感性的原则证明 和面包板小角度入射荧光系统的吞吐量。建议的第二期工程 为期24个月的项目是开发CL-XRFI的完整原型。