Advanced Imaging and Simulation Tools for Personalized Corneal Disease Assessment and Surgery

基于患者特定输入的模拟有可能推动个性化领域的重大进步 医药。然而，重要的差距仍然存在，必须在基于模拟的工程能够 在治疗角膜和屈光不正方面充分发挥杠杆作用。其中包括临床的发展。 用于生物力学表征的工具、测量和模拟系统的集成以及模型 验证和验证。在这项生物工程研究拨款中，我们将通过以下方式应对这些挑战 具体目标如下：目标1.发展用于三维表征的光学相干弹性成像(OCE 异种角膜生物力学特性。在这一发展目标下，我们将发展和 优化新的系统，能够1)体积区域采样；2)真正的3D位移跟踪；3) 同时测量眼压和粘弹性。该系统将被用来建立更敏感的 用于圆锥角膜(KC)的生物力学生物标志物，以及用于3D特性评估的逆向有限元模型。 目的2.结合3D OCE和逆向有限元建模对3D角膜进行表征和比较 正常、KC和手术改变状态下的生物力学特性。层析成像和3DOCE衍生 测量将用于建立和验证患者特定的FE模型。我们将引导人类 检验OCE来源的生物标志物将更好地区分KC和亚临床的假设的研究 来自正常眼的KC比可用的断层扫描和充气衍生的生物力学指标要好。我们还将 在KC进展的纵向研究中测量空间生物力学变化，并比较深度- 准分子激光原位角膜磨镶术、小切口晶状体摘除术和角膜的生物力学相关性变化 交联剂(CXL)。后一种比较将直接检验广为流传的微笑假说 与LASIK相比，造成的间质减弱更少。目标3.开发和评估特定于患者的计算 预测介入结果、KC进展和LASIK术后扩张症的模型。我们将测试 假设使用特定于对象的几何和材料属性数据填充的模型 手术结果指标、KC进展率和LASIK术后扩张率的准确预测 现有的方法。这些目标的顺利完成有望带来发展和立竿见影 翻译个性化精准医学框架，以便利用这些数据实现更有效 在关键临床条件下的诊断和个性化治疗计划。

Simulations based on patient-specific inputs have the potential to drive major advances in personalized medicine. However, important gaps persist that must be addressed before simulation-based engineering can be fully leveraged in the treatment of corneal and refractive disorders. These include development of clinical tools for biomechanical characterization, integration of measurement and simulation systems, and model validation and verification. In this Bioengineering Research Grant, we will address each of these challenges by the following specific aims: Aim 1. Develop optical coherence elastography (OCE) for 3D characterization of heterogenous corneal biomechanical properties. In this developmental aim, we will develop and optimize a new system capable of 1) volumetric regional sampling; 2) true 3D displacement tracking and 3) simultaneous IOP and viscoelastic property measurement. The system will be used to establish more sensitive biomechanical biomarkers for keratoconus (KC) and to inform inverse FE models for 3D property estimation. Aim 2. Integrate 3D OCE and inverse FE modeling to characterize and compare 3D corneal biomechanical properties in normal, KC, and surgically altered states. Tomography and 3D OCE-derived measurements will be used to establish and validate patient-specific FE models. We will conduct human studies to test the hypothesis that OCE-derived biomarkers will better discriminate manifest KC and subclinical KC from normal eyes than available tomography and air puff-derived biomechanical metrics. We will also measure spatial biomechanical changes during a longitudinal study of KC progression and compare depth- dependent biomechanical changes in LASIK, small-incision lenticule extraction (SMILE), and corneal crosslinking (CXL). The latter comparison will directly test the widely promulgated hypothesis that SMILE causes less stromal weakening than LASIK. Aim 3. Develop and evaluate patient-specific computational models for predicting interventional outcomes, KC progression, and post-LASIK ectasia. We will test the hypothesis that models populated with subject-specific geometry and material property data are more accurate predictors of surgical outcomes metrics, KC progression rate, and post-LASIK ectasia risk than existing methods. Successful completion of the aims is expected to lead to the development and immediate translation of a personalized precision-medicine framework for leveraging such data for more effective diagnosis and personalized treatment planning in key clinical conditions.