In vivo optical coherence elastography of the cornea: mapping shear and tensile moduli

摘要 角膜的机械稳定性通过维持角膜曲率来支持视力， 屈光手术和角膜扩张症治疗的重要意义。然而，临床上 机械特性的选择是有限的，特别是与成熟的工具相比 用于描述角膜的形态特征。一些商业和调查工具已经 强调了角膜生物力学分析的潜在价值，但这些设备的准确性有限 并且不能完全表征角膜的各向异性、非线性和空间变化的弹性刚度。 该项目的总体目标是开发先进的光学相干弹性成像(OCE)，用于 角膜生物力学的综合表征。这项拟议的技术既利用了 沿角膜引导的伸展和弯曲弹性波测量平面内拉伸(Young‘s)和 在毫米尺度分辨率下的剪切模数。第一个具体目标是开发一种使用非接触的OCE系统 经过优化的超声波换能器，可有效地在跨度为4-4英寸的高频下激发两种弹性波 10千赫。第二个具体目标是用健康的受试者测试这个OCE系统，并调查 体内拉伸和剪切模数与年龄和眼压的相关性。第三个具体目标是 测量诊断为圆锥角膜患者的拉伸和剪切模数并监测机械性能 角膜交联剂治疗后的变化。第四个具体目标是分析模块的变化 作为不同的角膜屈光手术的结果。各种体外测量和有限元 还将进行建模研究，以解释临床数据并将测量的数据联系起来 对角膜的微结构有一定的影响。这个项目将促进我们对角膜的理解 与各种自然、病理和介入过程有关的生物力学，并可能导致 可提高圆锥角膜诊断和治疗、安全性和可视的新临床工具 屈光手术的结果和眼压测量的准确性。

ABSTRACT The mechanical stability of the cornea supports visual acuity by maintaining corneal curvature, with important implications for refractive surgery and the management of cornea ectasia. However, clinical options for mechanical characterization are limited, particularly when compared to well-established tools for morphological characterization of the cornea. Several commercial and investigational instruments have highlighted the potential value of corneal biomechanical analysis, but these devices have limited accuracy and cannot fully characterize the anisotropic, nonlinear, and spatially varying elastic stiffness of the cornea. The overarching goal of this project is to develop advanced optical coherence elastography (OCE) for comprehensive characterization of corneal biomechanics. The proposed technology harnesses both extensional and flexural elastic waves guided along the cornea to measure in-plane tensile (Young’s) and shear moduli at mm-scale resolution. The first specific aim is to develop an OCE system using non-contact ultrasound transducers optimized to excite both elastic waves efficiently at high frequencies spanning 4- 10 kHz. The second specific aim is to test this OCE system with healthy subjects and investigate the dependence of tensile and shear moduli on age and intraocular pressure in vivo. The third specific aim is to measure tensile and shear moduli in patients diagnosed with keratoconus and to monitor mechanical changes after corneal crosslinking treatment. The fourth specific aim is to analyze changes in the moduli as a result of different corneal refractive surgeries. Various ex vivo measurements and finite-element modeling studies will also be undertaken in order to interpret the clinical data and relate the measured moduli to the microstructure of the cornea. This project will advance our understanding of corneal biomechanics in relation to various natural, pathological, and interventional processes and may lead to a new clinical tool that can improve the diagnosis and treatment of keratoconus, the safety and visual outcome of refractive surgery, and the accuracy of tonometry.