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: 10011049
• 负责人: Wenbing Yun
• 金额: $ 24.78万
• 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: 2020-05-01 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10011049
• 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; detector; fluorescence imaging; imaging system; improved; innovation; novel; novel therapeutics; phantom model; prevent; prototype; reconstruction; success; targeted treatment; theories; therapeutic development; therapeutic target; 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; detector; fluorescence imaging; imaging system; improved; innovation; novel; novel therapeutics; phantom model; prevent; prototype; reconstruction; success; targeted treatment; theories; therapeutic development; therapeutic target

Title: Development of a Quantitative Iron Characterization System for Alzheimer's Using Computed Laminography X-ray Fluorescence Imaging (CL-XRFI) Project Summary/Abstract 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.

标题：使用Alzheimer的定量铁表征系统的开发 计算的层压板X射线荧光成像（Cl-XRFI） 项目摘要/摘要 螺旋病的发现已激发了新的疗法，以预防和/或改变 大脑中的病理铁分布与阿尔茨海默氏病（AD）和其他 神经退行性疾病。为了有效评估新药设计，能够 需要直接成像并量化脑样品中铁的痕量水平。当前的 方法包括LA-ICPMS和同步物Microxrf，每个Microxrf都有自己的 在速度，数量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层压板X射线荧光成像的方案 （Cl-XRFI）。在这个新颖的系统设计中，X射线光束聚焦于铅笔状光束 以非常低的角度（3度）出现在样品上。探测器平行于 样品表面以最大化实体角度。获取在概念上与基于抽象的相似 层压扫描，其中以多个角度获取以重建信号 起源。该系统设计由公司专利的高亮度X射线启用 来源及其专有X射线光学技术，可提供较大的工作距离 该技术工作所必需的。 拟议的I期6个月项目是敏感性的原理证明证明 和面包板低角度荧光系统的吞吐量。提出的II期 24个月的项目是开发Cl-XRFI的完整原型。