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

用于个性化角膜疾病评估和手术的先进成像和模拟工具

• 批准号: 10644983
• 负责人: William Joseph Dupps
• 金额: $ 62.59万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10644983
• 关键词: 3-Dimensional; Address; Affect; Agreement; Air; Anterior; Biological Markers; Biomechanics; Biomedical Engineering; Blindness; Clinical; Computer Models; Computer Simulation; Cornea; Corneal Diseases; Data; Development; Diagnosis; Disease; Disease Progression; Early Diagnosis; Elements; Engineering; Eye; Geometry; Human; Image; Individual; Intervention; Keratoconus; Laser In Situ Keratomileusis; Longitudinal Studies; Maps; Measurement; Measures; Methods; Modeling; Nomograms; Operative Surgical Procedures; Optics; Outcome; Pathological Dilatation; Patients; Persons; Positioning Attribute; Postoperative Period; Probability; Procedures; Property; Refractive Errors; Relative Risks; Research; Research Project Grants; Retina; Risk; Risk Assessment; Sampling; Series; Shapes; Speed; Stress; Structural Models; Surgeon; Surgical incisions; System; Testing; Time; Translations; Variant; Visual; Work; biomechanical test; body system; clinical development; clinical investigation; corneal surgery; crosslink; disorder risk; elastography; in vivo; multidisciplinary; novel; novel marker; outcome prediction; personalized approach; personalized medicine; personalized predictions; precision medicine; predictive modeling; prognostic; programs; progression risk; simulation; surgery outcome; surgical risk; targeted imaging; three-dimensional modeling; tomography; tool; treatment planning; verification and validation; viscoelasticity; visual performance

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.

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 药品。然而，在基于仿真的工程能够实现之前，必须解决重要的差距。 充分利用角膜和屈光障碍的治疗。其中包括临床开发 用于生物力学表征、测量和模拟系统集成以及模型的工具 验证和验证。在这项生物工程研究补助金中，我们将通过以下方式解决这些挑战： 目标 1. 开发用于 3D 表征的光学相干弹性成像 (OCE) 异质角膜生物力学特性。为了这个发展目标，我们将开发和 优化新系统，该系统能够 1) 体积区域采样； 2) 真正的 3D 位移跟踪和 3) 同时测量眼压和粘弹性。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 属性估计的逆有限元模型提供信息。 目标 2. 集成 3D OCE 和逆 FE 建模来表征和比较 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 测量结果将用于建立和验证患者特定的有限元模型。我们将进行人性化 研究检验 OCE 衍生生物标志物将更好地区分明显 KC 和亚临床 KC 的假设 来自正常眼睛的 KC 与可用的断层扫描和吹气衍生的生物力学指标相比。我们也会 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、小切口微透镜摘除术 (SMILE) 和角膜的相关生物力学变化 交联（CXL）。后一个比较将直接检验广泛传播的假设：SMILE 与 LASIK 相比，引起的基质减弱较少。目标 3. 开发和评估针对患者的计算 预测介入结果、KC 进展和 LASIK 术后扩张的模型。我们将测试 假设模型填充了特定于主题的几何形状和材料属性数据 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带来发展并立即实现 翻译个性化精准医疗框架，以利用此类数据更有效 关键临床病症的诊断和个性化治疗计划。