脑组织不同脑区中铁、铜、锌等元素分布的异常与阿尔茨海默病(Alzheimer disease,AD）的成因、发展密切相关，实现AD脑组织中Fe、Cu、Zn元素的原位、微区绝对定量测量对于AD病理学研究具有重要意义。激光剥蚀电感耦合等离子体质谱（LA-ICP-MS）具有原位、微区分析能力，但由于基体效应、分馏效应的影响，应用到生物组织的原位、微区分析时，只能获得元素分布的相对强弱信息，不能给出微区分布的绝对含量。 本项目针对LA-ICP-MS难以实现原位绝对定量的难题，利用同位素稀释技术，开展生物组织样品与稀释剂同位素交换平衡、稀释剂形态及添加方式、原位的同位素测量等关键技术研究，建立基于同位素稀释技术的LA-ICP-MS在脑组织中Fe、Cu、Zn等元素原位、微区绝对定量方法，并应用于正常和AD鼠脑组织中相关元素的原位、微区绝对定量分析，结合微束X荧光技术，为AD病病理学研究提供技术支撑。

Previous studies showed that the imbalance of iron,coper and zinc distribution in brain has close relationship with the cause and development of Alzheimer disease (AD). To investigate the quantitative imaging of these elements in different brain regions can help to understand the pathological process of AD disease. Laser ablation (LA)-ICP-MS, due to its impressive detection limits and spatial resolution capacity in the micrometer range, is well established as a microprobe for elemental mapping in life sciences area. However, because of the calibration challenge, most research just focused on the intensity imaging. The studies on quantitative imaging were needed for further investigation. In this project, we will combine the isotope dilution with LA-ICP-MS to investigate the quantitative imaging methods of Fe, Cu and Zn in normal and AD rat brain. The conditions for enriched isotopic spike addition, isotope exchange and measurement of isotope ratio will be fully studied. Moreover, combined with the micro-XRF technics, the Fe, Cu and Zn quantitative image of normal and AD rat brain will be determined with the improved layout. This project will help to improve the accuracy of quantitative image by LA-ICP-MS, and has the potential to act as supplementary methods in the AD pathological research.