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.

铁下垂的发现激发了新的治疗方法来预防和/或改变