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治疗的重大进展。 药然而，重要的差距仍然存在，必须解决之前，基于仿真的工程可以 在角膜和屈光疾病的治疗中得到充分利用。其中包括临床开发 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 确认和验证。在这项生物工程研究资助中，我们将通过以下方式应对这些挑战： 具体目标如下：目标1。开发用于3D表征的光学相干弹性成像（OCE） 异质性角膜生物力学特性。在这一发展目标下，我们将发展和 优化一个新的系统，能够1）体积区域采样; 2）真正的3D位移跟踪和3） 同时测量IOP和粘弹性。该系统将用于建立更敏感的 圆锥角膜（KC）的生物力学生物标志物，并为3D属性估计提供逆FE模型。 目标二。集成3D OCE和逆FE建模，以表征和比较3D角膜 正常、KC和手术改变状态下的生物力学特性。断层扫描和3D OCE衍生 测量将用于建立和验证患者特定的FE模型。我们将进行人类 研究以检验OCE衍生的生物标志物将更好地区分明显KC和亚临床KC的假设。 KC从正常的眼睛比现有的断层扫描和空气吹衍生的生物力学指标。我们还将 在KC进展的纵向研究期间测量空间生物力学变化，并比较深度- LASIK、小切口小梁切除术（SMILE）和角膜移植术中的生物力学变化 交联（CXL）。后一项比较将直接检验广泛传播的假设，即微笑 比LASIK导致的基质弱化更少。目标3。开发和评估患者特定的计算 用于预测介入治疗结果、KC进展和LASIK术后扩张的模型。我们将测试 假设填充有对象特定几何形状和材料属性数据的模型 手术结果指标、KC进展率和LASIK术后扩张风险的准确预测因子， 现有的方法。成功完成这些目标预计将导致发展和立即 翻译个性化的精确医疗框架，以利用这些数据更有效地 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.