Ocular Pulse Elastography

预测继发于圆锥角膜或屈光手术的角膜扩张风险的努力将大大便利，如果 角膜生物力学特性的测量在活体内是可用的，以改进当前的诊断 仅根据结构(即地形和层析)评估。例如，机械 发现患者角膜(有或无地形性异常)的弱点(整体或局部) 可以提醒医生密切监测病情，并可能启动干预措施以阻止扩张症 进步。在临床上，获取空间分辨生物力学信息的能力仍然缺乏。许多 已经提出了一些方法，但它们通常依靠外力使角膜变形，以便 引起机械反应。此外，大多数方法没有显式地解决 眼压(IOP)对测量特性的影响。 在这个项目中，我们的目标是建立一种超声弹性成像技术，称为眼部脉冲弹性成像 (OPE)，以表征角膜对每个心动周期眼压周期性变化的反应，即 眼球脉搏。基线眼压和眼睛脉搏幅度都可以在体内测量，将用于 结合OPE的生物力学测量得出固有的组织生物力学特性 这些参数与IOP参数无关。我们的初步研究表明，OPE 基于高频超声射频数据分析的技术可以提供 0.05%或更好，使可靠地测量由眼部脉冲引起的体内小应变成为可能 几毫米汞柱。 在拟议的研究中，我们将(1)验证OPE技术对角膜的机械表征； (2)评价OPE检测临床相关角膜硬化的敏感性；(3)确定角膜硬化的分布 正常人及其年龄相关的OPE衍生角膜硬度参数的变化 改变；以及(4)检验圆锥角膜和角膜生物力学特性改变的预测 建立基于OPE的圆锥角膜生物力学指标。前两个目标将调查两者之间的关系 OPE措施与传统机械测试方法之间的差异，以及生理学测试的影响 变量和敏感度，在对照实验下建立我们对人眼OPE的知识 条件(即供者眼)，并提供最佳参数设置和框架 解释活体数据。拟议研究的最后两个目标将带来知识和技术 从长凳到床边，获取正常角膜和圆锥角膜患者的活体数据，如 确定OPE的临床应用并确定新的、敏感的生物力学指标治疗扩张症的第一步 风险。 拟议的研究将解决对角膜进行体内体积生物力学评估的需要， 导致了一种临床工具，用于识别和监测生物力学不稳定或减弱，以帮助 扩张性疾病的诊断和治疗。更广泛地说，这项拟议的研究将影响眼科领域 生物力学，通过生成活体技术和数据来更好地了解生物力学是如何涉及的 在眼睛的健康和疾病方面。

Efforts to predict corneal ectasia risk secondary to keratoconus or refractive surgery will be greatly facilitated if the measures of corneal biomechanical properties are made available in vivo to improve current diagnoses based on structural (i.e., topographic and tomographic) evaluations alone. For example, mechanical weaknesses (overall or regional) identified in patients’ corneas (with or without topographical abnormalities) could alert physicians to closely monitor the condition and potentially initiate interventions to arrest ectatic progression. Clinically, the ability to acquire spatially resolved biomechanical information is still lacking. Many approaches have been proposed, but they often rely on an external force to deform the cornea in order to induce a mechanical response. In addition, most methods do not explicitly address the influence of the intraocular pressure (IOP) on the measured properties. In this project, we aim to build an ultrasound elastographic technique, termed as the ocular pulse elastography (OPE), to characterize the cornea’s response to the cyclic variation of IOP at each cardiac cycle, i.e., the ocular pulse. The baseline IOP and ocular pulse amplitude, which are all measurable in vivo, will be used in combination with the biomechanical measures from OPE to derive the intrinsic tissue biomechanical properties that are independent of the IOP parameters. Our preliminary studies have demonstrated that the OPE technique, based on high frequency ultrasound radiofrequency data analysis, can provide a strain resolution of 0.05% and better, making it possible to reliably measure small in vivo strains induced by an ocular pulse of a few mmHg. In the proposed research, we will (1) validate the OPE technique for mechanical characterization of the cornea; (2) evaluate the sensitivity of OPE in detecting clinically relevant corneal stiffening; (3) define the distribution and variance of OPE-derived corneal stiffness parameters in normal human subjects and their age-associated changes; and (4) test the prediction that corneal biomechanical properties are altered in keratoconus and develop OPE-based biomechanical indices for keratoconus. The first two aims will investigate the relationship between OPE measures and those from traditional mechanical testing, as well as the effects of physiological variables and sensitivity, to build our knowledge of OPE in human eyes under controlled experimental conditions (i.e., in donor eyes) and provide optimal parametric settings and framework for acquiring and interpreting in vivo data. The last two aims of the proposed research will bring the knowledge and technique from the bench to the bedside to acquire in vivo data from normal corneas and those with keratoconus, as the first step of establishing OPE’s clinical use and identifying new, sensitive biomechanical metrics for ectasia risks. The proposed research will address the need for in vivo volumetric biomechanical evaluation of the cornea, leading to a clinical tool for identifying and monitoring biomechanical instability or weakening to aid the diagnosis and treatment of ectatic disease. More broadly, the proposed research will impact the field of ocular biomechanics, by generating in vivo techniques and data to better understand how biomechanics are involved in the health and disease of the eye.