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

该项目将开发和展示一种独特的活组织成像平台，该平台可以检测小鼠活脑片中阿片类药物的存在，并成像它们对细胞代谢和耦合的神经大脑活动的影响。这一平台将首次可视化阿片类药物的存在如何影响神经元和星形胶质细胞的新陈代谢，以及随后的神经自发去极化活动。这一成像平台的建立和演示将使未来能够使用吗啡(典型的阿片类药物)、咖啡因和多巴胺进行比较研究，以阐明阿片类药物与非成瘾化合物(例如咖啡因和麻醉剂)以及普遍存在的神经递质(例如多巴胺)在调节大脑细胞代谢方面的不同之处。该项目将影响阿片成瘾和相关的神经科学，并影响涉及不同疾病、器官和临床前模型的药物开发的更广泛研究。当阿片类药物被感兴趣的药物取代时，拟议的成像平台将一般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界/工程界和制药界以及在外联活动中广泛的社会阶层之间分享。新的成像和可视化能力将启发K-12学生思考如何利用技术来促进科学调查。外展活动将包括通过年度工程开放参观活动向社区团体演示该成像平台，以及将这些技术方法整合到博帕特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NSF的法定使命，并通过使用基金会的智力优势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.