Optical imaging of retinal structure and function with cellular resolution

光学成像工具已经彻底改变了人类视网膜成像，为临床医生提供了视网膜的新视角。将这项技术应用于临床前成像，使得纵向研究能够了解疾病机制，并评估正在开发的治疗方法的效果。然而，现有的工具不能满足分辨率和功能成像能力的要求，视觉科学家仍然严重依赖离体组织学。本研究计划提案的目的是研究新技术，将三种成像技术集成到一个单一系统中。我们建议使用可见光波长的光源进行光学相干断层扫描（OCT），这是一种提供视网膜结构3D图像的成像技术。从高速OCT系统体积中提取的人脸图像将用作无波前传感器自适应光学（WS AO）配置中的图像质量度量，以将横向分辨率提高到所研究眼睛的数值孔径允许的极限。通过适当选择OCT的波长范围，可以使用相同的光源来激发视网膜中的荧光报告分子。利用WS AO提供的高分辨率和共聚焦检测，荧光标记的三维位置将通过覆盖在OCT体积结构成像上而可视化。这种多模式系统将通过对视网膜基因治疗的研究来证明。本研究将建立一个原型系统，以协助实验室研究糖尿病视网膜病变导致视力丧失的新治疗方法。这一项目的影响是一种新的成像技术，将加速导致失明的疾病的新疗法的临床前开发。通过该提案开发的技术在未来转化为人类视网膜成像方面也具有强大的潜力。

Optical imaging tools have revolutionized human retinal imaging, providing clinicians with a new view of the retina. Thetranslation of this technology for preclinical imaging has enabled longitudinal studies to understand disease mechanisms andevaluate the effects of therapies that are under development. However, the available tools do not meet the requirements ofresolution and functional imaging capability, and vision scientists still rely heavily on ex vivo histology. The purpose of thisresearch project proposal is to investigate novel technology, integrating three imaging techniques into a single system. Wepropose to use a light source with visible wavelengths for optical coherence tomography (OCT), an imaging technique thatprovides 3D images of the retinal structure. En face images extracted from the high speed OCT system volumes will be usedas an image quality metric in a wavefront-sensorless adaptive optics (WS AO) configuration to increase the lateral resolutionto the limits permitted by the numerical aperture of the eye under investigation. Through appropriate selection of thewavelength range for the OCT, the same light source can be used for excitation of fluorescent reporter molecules in theretina. With the high resolution provided by the WS AO and confocal detection, the 3D location of the fluorescent labels willbe visualized by overlay on the OCT volumetric structural imaging. This multimodal system will be demonstrated through theinvestigation of gene therapy in the retina. A prototype system will be constructed for knowledge translation to acollaborating laboratory to investigate novel treatments for vision loss due to diabetic retinopathy. The impact of this projectis a novel imaging technology that will accelerate the preclinical development of new therapies for diseases causingblindness. The technology developed through this proposal also has strong potential for future translation to human retinalimaging.