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.

铁下垂的发现已经证实了新的治疗方法来预防和/或改变铁下垂。 脑中的病理性铁分布与阿尔茨海默病（AD）和其他疾病相关， 神经退行性疾病为了有效地评估新药设计， 需要直接成像和定量脑样品中痕量水平的铁。电流 方法包括LA-ICPMS和同步加速器microXRF，它们各自具有它们自己的 在速度、量化可靠性和可访问性方面的缺点。 我们建议开发一种称为计算机断层X射线荧光成像的方案 （CL-XRFI）。在这种新颖的系统设计中，X射线束被聚焦成类似于激光束的光束 以非常低的角度（3度）入射到样品上。探测器平行于 样品表面以最大化立体角。收购在概念上类似于基于吸收 断层摄影，其中在多个角度采集以重建信号 起源该系统的设计是独特的启用该公司的专利高亮度x射线 源和其专有的x射线光学技术，提供了大的工作距离 这是这项技术发挥作用所必需的。 拟议的第一阶段6个月项目是对敏感性的原理证明 和通过量。拟议的第二阶段 24-一个月的项目是开发一个完整的原型CL-XRFI。