Ocular Pulse Elastography

 描述(申请人提供)：眼球脉冲弹性成像将极大地促进预测继发于圆锥角膜或屈光手术的角膜扩张风险的努力，如果体内可获得角膜生物力学特性的测量，以改善仅基于结构(即，地形图和断层扫描)评估的当前诊断。例如，在患者角膜中发现的机械弱点(整体或局部)(有或没有地形异常)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性进展。在临床上，获取空间分辨生物力学信息的能力仍然缺乏。已经提出了许多方法，但它们通常依靠外力使角膜变形，以诱导机械反应。此外，大多数方法没有明确考虑眼压(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，称为眼球脉冲弹性成像(OPE)，以表征角膜对每个心脏周期(即眼球脉冲)眼压周期性变化的响应。基线眼压和眼脉搏幅度都可以在体内测量，将与OPE的生物力学测量结合使用，以得出与眼压参数无关的内在组织生物力学特性。我们的初步研究表明，基于高频超声射频数据分析的OPE技术可以提供0.05%或更好的应变分辨率，使得可靠地测量几毫米汞柱眼球脉冲引起的体内小应变成为可能。在拟议的研究中，我们将(1)验证OPE技术用于角膜机械表征；(2)评估OPE在检测临床相关角膜硬化方面的敏感性；(3)确定OPE衍生的角膜硬度参数在正常人中的分布和变化及其年龄相关变化；以及(4)检验圆锥角膜中角膜生物力学特性发生变化的预测，并开发基于OPE的圆锥角膜生物力学指标。前两个目标将研究OPE测量与传统机械测试之间的关系，以及生理变量和灵敏度的影响，以建立我们对受控实验条件下(即供体眼)人眼OPE的知识，并为获取和解释活体数据提供最佳参数设置和框架。这项拟议研究的最后两个目标将把从工作台上获得正常角膜和圆锥角膜患者体内数据的知识和技术带到床边，作为建立OPE的临床应用和确定新的、敏感的生物力学指标来评估扩张风险的第一步。这项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，从而产生一种临床工具，用于识别和监测生物力学不稳定或变弱，以帮助诊断和治疗扩张性疾病。更广泛地说，这项拟议的研究将通过产生体内技术和数据来影响眼睛生物力学领域，以更好地了解生物力学如何涉及眼睛的健康和疾病。

 DESCRIPTION (provided by applicant): Ocular Pulse Elastography 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 acquie 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.