Noninvasive Imaging of Chorioretinal Oxygen Tension

描述（由申请人提供）：视网膜细胞的代谢功能基于绒毛膜视网膜循环提供的营养物质和氧气的可用性。视网膜缺氧与糖尿病视网膜病变和老年性黄斑变性等主要和常见致盲性人眼疾病的发生有关。然而，脉络膜和视网膜血管在健康和疾病中对视网膜氧化的相对贡献尚未得到充分研究。此外，氧在视网膜疾病及其相关血管病变发展中的作用尚不清楚。因此，评估视网膜氧化的技术是非常需要的，以扩大知识，从而推进现有的诊断和治疗视网膜疾病的程序。一种利用氧敏感微电极测量视网膜氧张力的方法是可用的，但它是侵入性的，没有临床应用的潜力。基于氧敏感分子探针的磷光发射的血管内氧张力成像已经得到证实，但深度识别有限。我们建议克服现有技术的局限性，将我们的光学切片视网膜成像技术与磷光寿命成像技术相结合，提供视网膜血管和组织中氧张力的无创定量测量。具体目标是开发和建立一种新的成像系统，用于生成脉络膜血管和视网膜组织中氧张力的三维图像，确定视网膜氧张力时空变化的正常基线，基于磷光图像获得并验证视网膜耗氧量测量，并通过绘制视网膜氧张力梯度和血管模式来评估视网膜内耗氧量。本研究将为正常视网膜氧张力测量提供基础，为今后研究视网膜疾病动物模型的变化提供必要的基础。一旦改进，该技术将成为研究与疾病相关的氧动力学的有价值的工具，从而可以显著影响视网膜疾病的病理生理学，诊断和治疗的理解。

DESCRIPTION (provided by applicant): The metabolic function of the retinal cells is based on the availability of nutrients and oxygen that are supplied by the chorioretinal circulations. Retinal hypoxia is implicated in the development of major and common blinding human eye diseases, such as, diabetic retinopathy and age-related macular degeneration. However, the relative contribution of the choroidal and retinal vasculatures to the retinal oxygenation in health and disease has not been adequately studied. Moreover, the role of oxygen in the development of retinal diseases, and their associated vascular pathologies, is not well-understood. Therefore, technologies for assessment of retinal oxygenation are greatly needed to broaden knowledge, and thereby advance the available diagnostic and therapeutic procedures for retinal diseases. A method for retinal oxygen tension measurement that utilizes oxygen-sensitive microelectrodes is available, but is invasive and does not have the potential to be clinically applicable. Imaging of intravascular oxygen tension based on phosphorescence emission from an oxygen-sensitive molecular probe has been demonstrated, but with limited depth discrimination. We propose to overcome the limitations of the available techniques by combining our technique of optical section retinal imaging with phosphorescence lifetime imaging to provide noninvasive and quantitative measurements of oxygen tension in the retinal vasculatures and tissue. The specific aims are to develop and establish a novel imaging system for generating three-dimensional images of oxygen tension in the chorioretinal vasculatures and retinal tissue, to determine normal baselines for spatial and temporal variations in retinal oxygen tension, to obtain and validate retinal oxygen consumption measurements based on phosphorescence images, and to assess inner retinal oxygen consumption by mapping of retinal oxygen tension gradients and vasculature patterns. The proposed studies will provide a foundation for retinal oxygen tension measurements in normal retinas that is necessary for investigating variations in animal models of retinal diseases in the future. Once refined, the technique will serve as a valuable tool for investigating disease-related oxygen dynamics, and thereby, can significantly impact the understanding of the pathophysiology, diagnosis and treatment of retinal diseases.