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的重大进展 药品。但是，在基于模拟的工程可以解决之前必须解决重要的差距 完全利用角膜和折射率的治疗。这些包括临床的发展 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赠款中，我们将通过 以下具体目的：目标1。开发光学相干弹性图（OCE）以进行3D表征 异质角膜生物力学特性。在这个发展目标中，我们将发展并 优化能够1）体积区域采样的新系统； 2）TRUE 3D位移跟踪和3） 同时进行IOP和粘弹性属性测量。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FE模型提供信息。 AIM 2。整合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 测试OCE衍生的生物标志物将更好地区分明显KC和亚临床的研究的研究 来自正常眼睛的KC比可用的层析成像和空气泡芙的生物力学指标。我们也会 测量在KC进展的纵向研究期间的空间生物力学变化，并比较深度 LASIK，小牙皮提取（微笑）和角膜的依赖生物力学变化 交联（CXL）。后一个比较将直接检验广泛颁布的假设，即微笑 与lasik相比，导致基质较弱。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 ectasia的模型。我们将测试 用特定特定几何形状和材料属性数据填充的模型的假设更多 精确预测手术结果指标，KC进展率和Lasik后的风险比 现有方法。预计成功完成目标将导致发展和立即的发展 个性化精密中等医学框架的翻译，以利用此类数据以更有效 在关键临床状况下的诊断和个性化治疗计划。