Oxygen imaging by phosphorescence quenching

通过磷光猝灭进行氧成像的资源 项目摘要 组织氧合的实时、微创和空间分辨测量具有 有可能改变我们对许多临床问题的理解，包括肿瘤生物学中的问题， 中风管理、眼科、组织再生等等。多年来，我们的实验室 开发了一种微创方法，用于生物系统中氧气的动态成像，称为 磷光猝灭血氧测定法最近，该方法已被双光子扩展， 磷光寿命显微镜（2 PLM），能够在3D中动态成像组织中的氧梯度 具有微米级的分辨率，为神经科学、干细胞生物学、癌症 免疫学、组织工程和其他一些领域。甚至最近， 切伦科夫激发发光扫描成像（CELSI）的磷光使断层扫描成为可能 在接受放射治疗的组织中，在临床前环境中的3D氧气。与此同时， 基于磷光的血氧测定法因其潜力而越来越受到医学界的关注 直接评估创伤下组织的生理状态，优化输血效果， 监测光动力和放射治疗进展的标志物。这些和其他应用程序具有 为磷光技术在不同生物医学领域的广泛传播奠定了基础。 磷光猝灭法的核心是特殊的氧探针， 在我们的实验室中不断优化。这些探针的合成，包括最新的和最 有效的探针Oxyphor 2 P并不简单，标准的商业化途径目前也不可行。 在这里，我们建议建立一个U24资源，使我们能够维持磷光合成 探针，使它们可用于不同领域的广泛的生物医学研究人员。 同时，我们将生成通过磷光寿命测量/成像氧的软件，并将 建立一个中心，为对该方法感兴趣的新用户提供咨询和培训。这项工作将 在两个密切合作的网站进行：宾夕法尼亚大学（探针化学，软件 MGH的Martinos生物医学成像中心（软件开发，用户培训）。 我们的实验室有着悠久的生产合作历史以及多种合作和联系 对氧气感兴趣的研究人员。这些合作沿着过去的经验， 神经科学研究资源将帮助我们建立一个有效的计划，使磷光- 广泛的用户群可以使用的基于血氧测定的方法。

A Resource for Oxygen Imaging by Phosphorescence Quenching Project Summary Real-time, minimally invasive and spatially resolved measurements of tissue oxygenation have the potential to transform our understanding of many clinical problems, including those in tumor biology, management of stroke, ophthalmology, tissue regeneration, to name a few. Over the years our laboratory has developed a minimally invasive method for dynamic imaging of oxygen in biological systems, known as phosphorescence quenching oximetry. Recently, the method has been expanded by two-photon phosphorescence lifetime microscopy (2PLM), enabling dynamic imaging of oxygen gradients in tissues in 3D with micron-scale resolution, opening new horizons for research in neuroscience, stem cell biology, cancer immunology, tissue engineering and several other areas. Even more recently, the combination of phosphorescence with Cherenkov-Excited Luminescence Scanned Imaging (CELSI) enabled tomography of oxygen in 3D in pre-clinical setting in tissues undergoing radiation therapy. At the same time, phosphorescence-based oximetry is increasingly drawing attention from the medical community for its potential to directly evaluate physiologic status of tissue under trauma, optimize efficacy of blood transfusion as well as a marker in monitoring progress of photodynamic and radiation therapies. These and other applications have set the stage for broad dissemination of the phosphorescence technology across different biomedical fields. At the heart of the phosphorescence quenching method are special oxygen probes, developed and continuously optimized in our laboratory. The synthesis of these probes, including the newest and the most potent probe Oxyphor 2P, is not simple, and standard commercialization pathways are presently not feasible. Here we propose to establish a U24 Resource that would allow us to sustain synthesis of phosphorescent probes, making them available to a broad range of biomedical researchers across different fields. Simultaneously, we will generate software for measuring/imaging oxygen by phosphorescence lifetime and will establish a center to provide consultations and training of new users interested in the method. The work will be performed at two closely collaborating sites: the University of Pennsylvania (probe chemistry, software development) and Martinos Center for Biomedical Imaging at the MGH (software development, user training). Our laboratories have long history of productive collaboration as well as multiple collaborations and contacts with researchers interested in oxygen. These collaborations along with the past experience of running a neuroscience research resource will help us to establish an effective program, making the phosphorescence- based oximetry accessible to a broad user base.