Oxygen imaging by phosphorescence quenching

一种用于磷光猝灭的氧成像光源 项目摘要 实时、微创和空间分辨率的组织氧合测量具有 有可能改变我们对许多临床问题的理解，包括肿瘤生物学方面的问题， 中风的管理，眼科，组织再生，仅举几例。多年来，我们的实验室已经 开发了一种对生物系统中的氧气进行动态成像的微创方法，称为 磷光猝灭血氧法。最近，这种方法被扩展为双光子。 磷光寿命显微镜(2PLM)，实现组织中氧梯度的3D动态成像 具有微米级的分辨率，为神经科学、干细胞生物学、癌症的研究开辟了新的视野 免疫学、组织工程学和其他几个领域。甚至在最近，两项技术的结合 切伦科夫激发发光扫描成像(CELSI)的磷光层析成像 在接受放射治疗的组织中，临床前环境中的3D氧气。同时， 基于磷光的血氧测定仪因其潜力越来越受到医学界的关注 直接评估创伤组织的生理状态，优化输血效果 监测光动力和放射治疗进展的标志物。这些应用程序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。 磷光猝灭方法的核心是特殊的氧探针，开发和 在我们的实验室中不断优化。这些探针的合成，包括最新的和最新的 有效的探针Oxyphor 2P，并不简单，标准的商业化途径目前还不可行。 在这里，我们建议建立一个U24资源，使我们能够维持磷光的合成 探头，使它们可供不同领域的广泛生物医学研究人员使用。 同时，我们将生成通过磷光寿命测量/成像氧气的软件，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。这项工作将是 在两个密切合作的地点进行：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富有成效的合作历史以及多种合作和接触 研究人员对氧气感兴趣。这些合作以及过去运营 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- 以血氧计为基础，可供广大用户使用。

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.