EAGER: Optical Molecular Imaging of Opioid Distribution and its Metabolic Effects in the Brain

该项目将开发并展示一种独特的活体组织成像平台，该平台可以检测小鼠活体脑切片中阿片类药物的存在，并成像其对细胞代谢和耦合神经脑活动的影响。该平台将首次可视化阿片样物质的存在如何影响神经元和星形胶质细胞的代谢，以及随后的神经自发去极化活动。该成像平台的建立和演示将使未来使用吗啡（原型阿片类药物），咖啡因和多巴胺的比较研究能够阐明阿片类药物与非成瘾性化合物（如咖啡因和麻醉剂）和流行的神经递质（如多巴胺）如何不同，以调节大脑的细胞代谢。该项目将影响阿片类药物成瘾和相关神经科学，并影响涉及不同疾病、器官和临床前模型的更广泛的药物开发研究。当阿片类药物被感兴趣的药物替代时，所提出的成像平台将普遍适用于通过临床前成像进行药物筛选和发现。该项目的成果将在科学/工程和制药社区之间分享，并在广泛的社会领域中进行推广活动。新的成像和可视化功能将激发K-12学生思考如何利用技术来造福科学研究。外展活动包括通过年度工程开放日活动向社区团体展示该成像平台，以及将这些技术方法整合到Boppart教授的本科生物光子学和生物医学成像课程中。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This project will develop and demonstrate a unique live-tissue imaging platform that can detect the presence of opioids in live brain slices from mice, and image their effects on the cellular metabolism and coupled neural brain activity. This platform will allow the first visualization of how the presence of opioids affects the metabolism of neurons and astrocytes, and the subsequent neural spontaneous depolarization activity. The establishment and demonstration of this imaging platform will enable future comparative studies using morphine (the prototypical opioid), caffeine, and dopamine to elucidate how opioids differ from non-addictive compounds (e.g. caffeine and anesthetics) and prevalent neurotransmitters (e.g. dopamine) to modulate the cellular metabolism of the brain.This project will impact opioid addiction and related neuroscience and impact the broader research of drug development involving different diseases, organs, and preclinical models. The proposed imaging platform will be generally applicable to drug screening and discovery through preclinical imaging when the opioid is replaced by the drug of interest. The results of this project will be shared amongst the scientific/engineering and pharmaceuticalcommunities, and across wide segments of society in outreach activities. The new imaging andvisualization capabilities will inspire K-12 students to think about how technology can be used to benefit scientific investigations. Outreach activities will include demonstrations of this imaging platform to community groups through annual Engineering Open House events, as well as integration of these technological methods in Prof. Boppart's undergraduate Biophotonics and Biomedical Imaging courses.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.