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.

铁死亡的发现激发了预防和/或改变铁死亡的新疗法 大脑中的病理性铁分布与阿尔茨海默病（AD）和其他疾病相关 有效评估新的药物设计和技术。 需要直接对大脑样本中的痕量铁进行成像和定量。 方法包括 LA-ICPMS 和同步加速器 microXRF，每种方法都有自己的特点 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断层扫描 X 射线荧光成像的方案 (CL-XRFI) 在这个新颖的系统设计中，X 射线束被聚焦成铅笔状光束。 以非常低的角度（3 度）入射到样品上。 采样表面以最大化立体角的采集在概念上类似于基于吸收的采集。 层析成像，其中以多个角度进行采集以重建信号 该系统设计是由该公司获得专利的高亮度 X 射线独特实现的。 源及其专有的 X 射线光学技术可提供较大的工作距离 该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敏感性的原理验证论证 以及试验板低角度入射荧光系统的吞吐量。 为期24个月的项目是开发CL-XRFI的完整原型。