Visible-light OCT angiography, velocimetry, and oximetry for characterizing retinal vascular alterations in glaucoma

项目摘要 青光眼对视神经的损害和视力损害是进行性的和不可逆转的。理解 青光眼损伤的机制将有助于开发新的治疗方法，可用于 使用降低眼压的传统疗法。光学相干性的最新发展 断层扫描(OCT)血管造影术引起了人们对视网膜内循环在 青光眼。为了提高我们对青光眼视网膜血管改变的了解，我们可以利用 可见光OCT(VIS-OCT)同时表征组织结构、血管的研究进展 密度、血流量和氧合。该项目的目标是通过实现以下目标来进一步推进OCT 毛细血管水平测量，测试测量其局部变化作为青光眼早期指标的价值 和青光眼的进展，并用这一点来评估视网膜神经节的视网膜自动调节受损 细胞(RGC)丢失是进展期青光眼易感性增加的潜在原因。 在具体目标1中，我们将开发高速、高灵敏度、高分辨率的VIS-OCT。速度将会是 是目前系统的两倍。将使用更稳定的超连续激光来改进系统 为了提高横向分辨率，将使用更高的感光度和更紧的焦距。这将使完全检测到 可能易受血管功能障碍影响的毛细血管。 特指目标2将发展定量OCT血管造影，速度测量和血氧测定仪，以及 动脉和静脉。在AIM 1获得的高分辨率、高对比度扫描的基础上，我们将使用机器 学习如何分割毛细血管丛，以及先进的图像处理技术来提取毛细血管结构。受助人员 通过这种毛细血管架构，我们将自动测量毛细血管节段的血流量和血氧含量 并将它们整合到一个实时平台中。 特殊目标3将使用该系统演示由视神经产生的视网膜节细胞急性丢失 随着时间的推移，横切术改变了视网膜毛细血管丛密度、血氧仪和血流速度计，这些变化 在改变血氧饱和度和在较大视网膜血管中流动之前。我们还将展示RGC的丢失会损害 对急性眼压挑战的自动调节反应。 在特定的目标4中，我们将演示在可控、高眼压模型中的视神经损伤 毛细管测速仪、血氧测定仪和自动调节的早期变化表明，它们在 晚期损伤，并展示这些观察的病理生理学后果。 这项新技术的成功开发将改进青光眼的早期诊断和治疗方法 检测进程。更好地了解导致视网膜血管疾病易感性增加的因素 晚期青光眼将使这些高度脆弱的患者的治疗方法得到改善。

Project Summary Glaucoma damage to the optic nerve and impairment of vision are progressive and irreversible. Understanding mechanisms of glaucomatous injury will help to develop new approaches for treatments that can be used along with traditional therapies that lower intraocular pressure (IOP). Recent developments in optical coherence tomography (OCT) angiography have brought increased attention to the role of the inner retinal circulation in glaucoma. To improve our understanding of retinal vascular alterations in glaucoma, we can take advantage of recent developments in visible-light OCT (vis-OCT) to characterize simultaneously tissue structure, vessel density, blood flow and oxygenation. The goal of this project is to further advance vis-OCT by attaining capillary-level measurements, test the value of measuring their local alterations as early indicators of glaucoma and glaucomatous progression and use this to evaluate impaired retinal autoregulation from retinal ganglion cell (RGC) loss as a potential cause of increased susceptibility in advanced glaucoma. In Specific Aim 1 we will develop high-speed, high-sensitivity, high-resolution vis-OCT. The speed will be double that of the current system. A more stable supercontinuum laser will be used to improve system sensitivity, and a tighter focus will be used to improve lateral resolution. This will enable complete detection of capillaries that may be vulnerable to vascular dysfunction. Specific Aim 2 will develop quantitative OCT angiography, velocimetry and oximetry in capillaries as well as arteries and veins. Building on the high-resolution, high-contrast scans acquired in Aim 1, we will use machine learning to segment capillary plexuses, and advanced image processing to extract capillary architecture. Aided by this capillary architecture, we will automatically measure blood flow and oxygenation in capillary segments and incorporate them into a real-time platform. Specific Aim 3 will use this system to demonstrate that acute loss of RGCs, produced by optic nerve transection, alters retinal capillary plexus density, oximetry and velocimetry over time and that these changes precede altered oximetry and flow in larger retinal vessels. We will also show that loss of RGCs impairs the autoregulatory response to acute IOP challenge. In Specific Aim 4, we will demonstrate that optic nerve injury in a model of controlled, elevated IOP produces early alterations in capillary velocimetry, oximetry and autoregulation, show that they are more persistent with advanced injury, and demonstrate the pathophysiologic consequences of these observations. Successful development of this new technology will improve methods of early glaucoma diagnosis and detection of progression. Better understanding of retinal vascular factors that lead to increased susceptibility in advanced glaucoma will lead to improved treatments for these highly vulnerable patients.