Optical coherence elastography of corneal dynamics

 描述（由申请人提供）：角膜是高度组织化的胶原纤维分层（层状）结构，提供高抗张强度以保护眼睛和70%的屈光力。虽然物理性质与其主要光学功能、对手术干预的反应以及常规眼科检查（如眼内压测量）的结果密切相关，但角膜生物力学尚未成为主要研究兴趣的主题。角膜地形图、眼压测量、角膜厚度测量以及在较小程度上的光学相干断层扫描（OCT）是临床上用于角膜疾病筛查和屈光手术计划的主要非侵入性工具。然而，从最近的研究中可以清楚地看出，这些系统对实验条件非常敏感，并且不能用于绘制基本的角膜粘弹性参数。事实上，没有非侵入性测量工具可以提供每个人所需的信息，以开发可用于筛查、手术计划和治疗监测的角膜的个性化生物力学模型。在这里，我们提出了一种基于光学相干弹性成像（OCE）的工具，可以用一台仪器潜在地取代角膜厚度测量，眼压测量和地形图，并可以实现详细的，个性化的角膜生物力学模型。我们将采用动态OCE的临床可翻译方法，以足够的空间尺度提供基本粘弹性的空间图，从而可能实现角膜的详细生物力学模型。这种方法利用了我们团队开发的几项创新，包括相位敏感OCT（PhS-OCT）系统，其位移灵敏度优于100 pm，非接触和最小接触机械刺激方法利用了声辐射力（ARF）和光声（PA）的最新发展，以及使用编码激励和非球面透镜将位移测量的固有SNR增加一到两个数量级的技术。具体研究计划包括五个具体目标。首先，我们将增强我们目前的PhS-OCT系统，以提高空间分辨率和运动灵敏度，同时减少整体成像时间。向临床转化的最初举措将在目标2中进行，其中将研究远程和非接触方法以在角膜中发射宽带剪切波。同时，我们将在目标3中探索各种SNR增强技术，以显著提高整体SNR。在所有情况下，目标2和3中的方法将符合光学和超声暴露的所有安全指南。从动态位移图重建复弹性模量的当前方法将在目标4中扩展，以考虑角膜的有界几何形状。最后，我们将在目标5中研究人类供体角膜，以测试OCE是否可以提供粘弹性特性图，这些粘弹性特性图可以驱动生物力学模型，预测由于眼内压变化和手术干预等扰动引起的角膜形状变化。

 DESCRIPTION (provided by applicant): The cornea is a highly organized, layered (lamellae) structure of collagen fibrils providing both high tensile strength to protect the eye and 70% of it refractive power. Although physical properties are closely linked to its primary optical function, its response to surgical interventions, and the results of routine eye tests such as intraocular pressure measurements, corneal biomechanics has not been a topic of major research interest. Topography, tonometry, pachymetry, and to a lesser extent optical coherence tomography (OCT), are the primary non- invasive tools used clinically for corneal disease screening and refractive surgery planning. It is clear from recent studies, however, that these systems are highly susceptible to experimental conditions and cannot be used to map fundamental corneal viscoelastic parameters. Indeed, there are no non-invasive measurement tools that can provide the information needed on every individual to develop a personalized biomechanical model of the cornea that could be used for screening, surgical planning, and treatment monitoring. Here we propose a tool based on optical coherence elastography (OCE) that can potentially replace pachymetry, tonometry, and topography with a single instrument, and may enable detailed, personalized models of cornea biomechanics. We will pursue a clinically translatable approach using dynamic OCE to provide spatial maps of fundamental viscoelastic properties at a spatial scale sufficient to potentially enable detailed biomechanical models of the cornea. This approach leverages several innovations developed by our team, including a phase-sensitive OCT (PhS-OCT) system providing displacement sensitivity better than 100 pm, non-contact and minimally contact mechanical stimulation approaches leveraging recent developments in acoustic radiation force (ARF) and photoacoustics (PA), and techniques to increase the inherent SNR of displacement measurements by one-two orders of magnitude using coded excitation and non-spherical lenses. The specific research plan includes five specific aims. In the first, we will enhance our current PhS-OCT system to improve spatial resolution and motion sensitivity while simultaneously decreasing overall imaging time. The initial move toward clinical translation will be in Aim 2 where both remote and non-contact methods will be investigated to launch broadband shear waves in the cornea. In parallel, we will explore a wide range of SNR enhancement techniques in Aim 3 to significantly increase overall SNR. In all cases, methods in Aims 2 and 3 will conform to all safety guidelines for both optical and ultrasonic exposure. Current methods to reconstruct the complex elastic modulus from dynamic displacement maps will be extended in Aim 4 to account for the bounded geometry of the cornea. Finally, we will study human donor corneas in Aim 5 to test whether OCE can provide maps of viscoelastic properties that can drive biomechanical models predicting corneal shape changes due to perturbations such as intraocular pressure variations and surgical interventions.