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脉络膜视网膜循环提供的营养物质和氧气的可用性。视网膜缺氧与主要和常见的致盲性人类眼部疾病的发展有关，例如糖尿病视网膜病变和年龄相关性黄斑变性。然而，脉络膜和视网膜血管对健康和疾病中视网膜氧合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的发展中的作用还没有得到很好的理解。因此，非常需要用于评估视网膜氧合的技术来拓宽知识，从而推进视网膜疾病的可用诊断和治疗程序。利用氧敏微电极的视网膜氧张力测量方法是可用的，但是是侵入性的并且不具有临床应用的潜力。基于氧敏分子探针的磷光发射的血管内氧分压成像已经被证明，但深度分辨力有限。我们建议克服现有技术的局限性，通过结合我们的技术，光学部分视网膜成像与磷光寿命成像，提供非侵入性和定量测量的视网膜血管和组织中的氧分压。具体目的是开发和建立一种用于生成脉络膜视网膜血管和视网膜组织中氧张力的三维图像的新型成像系统，以确定视网膜氧张力的空间和时间变化的正常基线，以获得和验证基于磷光图像的视网膜氧消耗测量，并通过绘制视网膜氧张力梯度和脉管系统模式来评估内部视网膜氧消耗。这些研究将为正常视网膜的视网膜氧分压测量提供基础，这对于将来研究视网膜疾病动物模型的变化是必要的。一旦完善，该技术将成为研究疾病相关氧动力学的宝贵工具，从而可以显著影响对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.