Enabling widespread use of high resolution imaging of oxygen in the brain

 描述（由申请人提供）：能够广泛使用脑中氧的高分辨率成像。在微观水平上评估脑氧合有可能改变我们对重要临床问题的理解，如中风，阿尔茨海默病，痴呆症，慢性高血压和脑癌，促进新疗法的开发，并有助于改善临床成像和治疗方案。到目前为止，还没有技术能够在大脑中进行具有高空间和时间分辨率的显微氧成像。在过去的几年里，我们已经开发出一种方法，称为双光子磷光寿命显微镜的氧（2PLM），它具有独特的能力，实现这一利基。这是唯一的成像方法，允许高分辨率映射的脑氧合在真实的时间。 我们建议建立一个可持续的资源，用于传播2PLM的氧气，使其可供神经病学和神经科学不同领域的感兴趣的研究人员使用。2PLM是最先进的双光子增强磷光探针和双光子激光扫描显微镜的独特变体的组合。在这个项目中，我们将优化和扩大氧气探针的合成，使其可供感兴趣的用户使用。我们将把最近开发的专用商用电子元件整合到2PLM设置中。我们还将优化算法，并为那些有兴趣建立自己的2PLM系统的人制作用户友好的软件。此外，我们将组织一个资源中心，用户将能够接受培训和运行试点实验。 这项工作将在两个密切合作的地点进行： 宾夕法尼亚大学（探针化学）和MGH（成像设置）。我们的实验室有着悠久的生产合作历史。我们还与许多对氧成像感兴趣的研究人员广泛合作。这将使我们能够为资源中心建立有效的基础设施，使氧气技术的2PLM可供广泛的用户使用。

 DESCRIPTION (provided by applicant): Enabling widespread use of high resolution imaging of oxygen in the brain As. essment of brain oxygenation on the microscopic level has the potential to transform our understanding of important clinical problems, such as stroke, Alzheimer's disease, dementia, chronic hypertension, and brain cancer, facilitating the development of new therapies and helping to improve clinical imaging and treatment protocols. Until now, no technology has been capable of microscopic oxygen imaging in the brain with high spatial and temporal resolution. Over the past several years we have developed a method, termed two-photon phosphorescence lifetime microscopy of oxygen (2PLM), which has the unique capability of fulfilling this niche. This is the only imaging method that allows high resolution mapping of brain oxygenation in real time. We propose to establish a sustainable resource for the dissemination of 2PLM of oxygen, making it available to interested researchers across different fields of neurology and neuroscience. 2PLM is a combination of state-of-the-art two-photon enhanced phosphorescent probes and a unique variant of two- photon laser scanning microscopy. In this project we will optimize and scale up synthesis of the oxygen probes, making them available for interested users. We will incorporate recently developed, dedicated commercial electronic components into 2PLM setups. We will also optimize algorithms and produce user- friendly software for those interested in setting up their own 2PLM systems. In addition, we will organize a resource center where users will be able to receive training and run pilot experiments. The work will be performed at two closely collaborating sites: the University of Pennsylvania (probe chemistry) and MGH (imaging setup). Our laboratories have a long history of productive collaboration. We also collaborate broadly with many researchers across the field interested in oxygen imaging. This will allow us to establish an effective infrastructure for the resource center, making the 2PLM of oxygen technology accessible to a broad user base.