optoretinography (ORG)

  • 文章类型: Journal Article
    近年来,视网膜光成像已成为一种重要的视网膜功能成像方法,因为光诱发的光感受器的变化已被大量不同的OCT系统证实。全场扫频源光学相干层析成像(FF-SS-OCT)相位特别稳定,它是目前唯一足够灵敏的技术来检测内部丛状层(IPL)中的较小功能变化。然而,现有技术的FF-SS-OCT系统的分辨率不足以区分单个光感受器。这使得难以将杆与锥体分离。在这项工作中,我们通过将视杆和视锥的功能变化与相同的光刺激不同的时间动力学分离来规避这个问题。为此,建立了一个数学模型,将测量信号表示为两个脉冲响应的叠加。所开发的模型很好地描述了不同成像条件下的测量数据,并且能够分别分析两种感光体类型的灵敏度和时间动态。
    In recent years, optoretinography has become an important functional imaging method for the retina, as light-evoked changes in the photoreceptors have been demonstrated for a large number of different OCT systems. Full-field swept-source optical coherence tomography (FF-SS-OCT) is particularly phase-stable, and it is currently the only technique sensitive enough to detect the smaller functional changes in the inner plexiform layer (IPL). However, the resolution of state-of-the art FF-SS-OCT systems is not high enough to distinguish individual photoreceptors. This makes it difficult to separate rods from cones. In this work, we circumvent this problem by separating the functional changes in rods and cones by their different temporal dynamics to the same light stimulus. For this purpose, a mathematical model was developed that represents the measured signals as a superposition of two impulse responses. The developed model describes the measured data under different imaging conditions very well and is able to analyze the sensitivity and temporal dynamics of the two photoreceptor types separately.
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  • 文章类型: Journal Article
    在过去的几年里见证了视网膜光成像的快速发展,视网膜神经功能的光学测量,尤其是光感受器(Ph)。虽然它最近的发展很快,它代表了几十年来数百个实验的高潮。早期工作表明,视网膜外植体和Ph悬浮液的光学特性发生了可测量且可重复的变化,并揭示了它们背后的一些生物物理和生化机制。因此,这项工作为基于临床成像平台的最新工作提供了关键动力,其最终目标是改善眼科护理和简化新疗法的发现。本综述的第一部分包括对早期工作的选择性总结,并识别出四种从中产生的刺激诱发的光信号:从Ph的外段(OS)的膜盘散射的光的变化,由操作系统的前后边界散射的光的变化,OS中和附近的散射材料的重排,和操作系统长度的变化。在过去的十年里,所有这4种信号均继续使用已经在临床中使用或打算用于临床和转化的成像系统进行研究.这篇综述的第二部分讨论了这些成像模式,它们检测和量化感兴趣信号的潜力,以及影响其翻译承诺的其他因素。特别注意具有自适应光学(AO)的相敏光学相干断层扫描(OCT),一种方法,其中从单个Ph反射的光的振幅和相位都被监视,因为可见刺激被传递给它们。光的相位的记录被解码,以揭示操作系统中的可再现的变形模式,而振幅揭示了散射和结构重排的变化。该方法已在一些实验室中得到证明,并已用于测量杆和锥体的响应。能够检测对异构化小于0.01%的光色素的刺激的反应,这种技术可能会很快,非侵入性,以及在细胞水平上测量细微疾病相关功能障碍的客观方法,从而为视网膜疾病和康复提供一种全新的补充生物标志物。
    The past few years have witnessed rapid development of the optoretinogram-a noninvasive, optical measurement of neural function in the retina, and especially the photoreceptors (Ph). While its recent development has been rapid, it represents the culmination of hundreds of experiments spanning decades. Early work showed measurable and reproducible changes in the optical properties of retinal explants and suspensions of Ph, and uncovered some of the biophysical and biochemical mechanisms underlying them. That work thus provided critical motivation for more recent work based on clinical imaging platforms, whose eventual goal is the improvement of ophthalmic care and streamlining the discovery of novel therapeutics. The first part of this review consists of a selective summary of the early work, and identifies four kinds of stimulus-evoked optical signals that have emerged from it: changes in light scattered from the membranous discs of the Ph\'s outer segment (OS), changes in light scattered by the front and back boundaries of the OS, rearrangement of scattering material in and near the OS, and changes in the OS length. In the past decade, all four of these signals have continued to be investigated using imaging systems already used in the clinic or intended for clinical and translational use. The second part of this review discusses these imaging modalities, their potential to detect and quantify the signals of interest, and other factors influencing their translational promise. Particular attention is paid to phase-sensitive optical coherence tomography (OCT) with adaptive optics (AO), a method in which both the amplitude and the phase of light reflected from individual Ph is monitored as visible stimuli are delivered to them. The record of the light\'s phase is decoded to reveal a reproducible pattern of deformation in the OS, while the amplitude reveals changes in scattering and structural rearrangements. The method has been demonstrated in a few labs and has been used to measure responses from both rods and cones. With the ability to detect responses to stimuli isomerizing less than 0.01% of photopigment, this technique may prove to be a quick, noninvasive, and objective way to measure subtle disease-related dysfunction at the cellular level, and thus to provide an entirely new and complementary biomarker for retinal disease and recovery.
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