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的损害是进行性的和不可逆的。理解 昏迷损伤的机制将有助于开发新的治疗方法，可以沿着 降低眼内压（IOP）的传统疗法。光学相干性的最新进展 断层扫描（OCT）血管造影术已经引起了越来越多的关注，视网膜内循环的作用， 青光眼为了提高我们对青光眼视网膜血管改变的理解，我们可以利用 用于同时表征组织结构、血管 密度、血流和氧合。该项目的目标是通过实现以下目标来进一步推进vis-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 和青光眼进展，并使用此来评估视网膜神经节的视网膜自动调节受损 细胞（RGC）损失作为晚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。速度将是 是现行制度的两倍。将采用更稳定的超连续谱激光器来改进系统 灵敏度和更紧密的焦点将用于提高横向分辨率。这将使完整的检测 毛细血管可能容易受到血管功能障碍的影响。 Special Aim 2将开发定量OCT血管造影、速度测定和毛细血管血氧测定， 动脉和静脉。基于目标1中获得的高分辨率、高对比度扫描，我们将使用机器 学习分割毛细血管丛，以及先进的图像处理来提取毛细血管结构。辅助 通过这种毛细血管结构，我们将自动测量毛细血管段中的血流和氧合， 并将它们整合到一个实时平台中。 具体目标3将使用该系统来证明由视神经产生的RGC的急性丧失 横切，改变视网膜毛细血管丛密度，血氧饱和度和速度随着时间的推移，这些变化 在更大的视网膜血管中出现血氧饱和度和血流改变。我们还将表明RGC的丢失会损害 对急性IOP激发的自身调节反应。 在具体目标4中，我们将证明在受控的高眼压模型中， 毛细血管速度测定、血氧测定和自动调节的早期改变表明， 晚期损伤，并证明这些观察结果的病理生理后果。 这项新技术的成功开发将改善早期青光眼诊断的方法， 检测进展。更好地了解导致视网膜血管病变易感性增加的视网膜血管因素 晚期青光眼将改善对这些高度脆弱患者的治疗。

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.