Corneal Elastography and Patient-Specific Modeling for Simulation-based Therapy

用于基于模拟的治疗的角膜弹性成像和患者特异性建模

• 批准号: 8664399
• 负责人: William Joseph Dupps
• 金额: $ 38.83万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8664399
• 关键词: Address; Algorithms; Biomechanics; Biomedical Engineering; Characteristics; Clinical; Clinical Research; Collagen; Computer Simulation; Cornea; Corneal Diseases; Data; Dependency; Development; Disease; Elements; Eye; Finite Element Analysis; Geometry; Goals; Human; Individual; Intervention; Keratoconus; Keratoplasty; Laser In Situ Keratomileusis; Link; Maps; Measurement; Methods; Modeling; Operative Surgical Procedures; Optics; Outcome; Pathologic; Pathological Dilatation; Patients; Play; Procedures; Property; Quality of life; Research; Research Project Grants; Risk; Role; Shapes; Spatial Distribution; Testing; Translations; United States; Vision; Work; base; crosslink; disorder risk; elastography; models and simulation; novel; programs; public health relevance; regional difference; response; screening; simulation; tool; treatment response; treatment strategy

DESCRIPTION (provided by applicant): Corneal ectasia is a major cause of impaired vision-related quality of life in the United States and a leading indication for corneal transplantation. The lack of clinical tools for resolving biomechanical properties throughout the cornea is a critical barrier to understanding mechanisms of corneal instability and applying potentially transformative bioengineering approaches to risk screening and treatment optimization. The goal of this research program is to develop a robust OCT-based simulation platform for quantifying ectasia risk and predicting individual responses to a broad range of corneal treatments. The objective, which is aided by the sensitive link between corneal shape and visual function, is to identify the key structural predictors of ectatic disease and develop rationl approaches to customized crosslinking therapy through integrated patient- specific biomechanical measurement and modeling. The central hypothesis is that the magnitude and distribution of biomechanical properties in the cornea are key drivers of corneal shape. This hypothesis and the methods for testing it have been developed in part through the applicants' preliminary work in corneal optical coherence elastography (OCE) and in patient-specific finite element (FE) analysis studies that suggest important dependencies between material properties and shape. The hypothesis will be tested through the following specific aims: 1) Characterize the magnitude and distribution of corneal biomechanical properties across normal, surgically altered and pathologic states, 2) determine the accuracy of elastography-driven FE models for predicting outcomes of corneal interventions in donor eyes and patients, and 3) identify the key biomechanical drivers of keratoconus progression, post-refractive surgery ectasia, and crosslinking response using patient-specific simulations. Under Aim 1, OCE will be used in donor eye and clinical studies to test the hypothesis that the human cornea has intrinsic regional differences in biomechanical properties that are altered in characteristic ways by LASIK, keratoconus and collagen crosslinking. After generating FE models using subject-specific geometry for all pre-intervention eyes in Aim 1, Aim 2 will test the hypothesis that models populated with subject-specific OCE property data better predict outcomes than those with idealized bulk property estimates. Finally, in large-scale, multifactorial FE simulations using al normal and keratoconic patients as modeling substrates, Aim 3 will determine how elastic properties, initial corneal geometry and procedure variables interact to influence ectasia risk and crosslinking responses. Expected outcomes include clinical translation of OCT-based capabilities for mapping corneal biomechanical properties and generating patient-specific computational models capable of predicting treatment responses. Simulation-based optimizations will support novel, customizable calculators for ectasia risk and new algorithms for enhancing the effects of collagen crosslinking in individual eyes. These outcomes directly address gaps identified by the NEI and will enable new simulation-based treatment strategies for existing and emerging corneal procedures.

描述（由申请人提供）：角膜扩张是美国视力相关生活质量受损的主要原因，也是角膜移植的主要适应症。 缺乏解决整个角膜生物力学特性的临床工具是理解角膜不稳定机制和应用潜在变革性生物工程方法进行风险筛查和治疗优化的关键障碍。 该研究项目的目标是开发一个基于 OCT 的强大模拟平台，用于量化扩张风险并预测个体对各种角膜治疗的反应。 在角膜形状和视觉功能之间的敏感联系的帮助下，目标是确定扩张性疾病的关键结构预测因素，并通过综合患者特异性生物力学测量和建模开发合理的定制交联治疗方法。 中心假设是角膜生物力学特性的大小和分布是角膜形状的关键驱动因素。 这一假设及其测试方法部分是通过申请人在角膜光学相干弹性成像（OCE）和患者特异性有限元（FE）分析研究中的初步工作而开发的，这些研究表明材料特性和形状之间存在重要的依赖性。 该假设将通过以下具体目标进行检验：1) 表征正常、手术改变和病理状态下角膜生物力学特性的大小和分布，2) 确定弹性成像驱动的有限元模型用于预测供体眼睛和患者角膜干预结果的准确性，3) 确定圆锥角膜进展、屈光手术后扩张的关键生物力学驱动因素，以及 使用患者特定模拟进行交联反应。 在目标 1 下，OCE 将用于供体眼睛和临床研究，以检验以下假设：人类角膜在生物力学特性方面具有内在的区域差异，这些差异通过 LASIK、圆锥角膜和胶原交联以特有的方式改变。 在目标 1 中使用针对所有干预前眼睛的特定于受试者的几何形状生成 FE 模型后，目标 2 将测试以下假设：使用特定于受试者的 OCE 属性数据填充的模型比使用理想化批量属性估计的模型更好地预测结果。 最后，在使用所有正常和圆锥角膜患者作为建模基底的大规模多因素有限元模拟中，目标 3 将确定弹性特性、初始角膜几何形状和手术变量如何相互作用以影响角膜扩张风险和 交联反应。 预期成果包括基于 OCT 的功能的临床转化，用于绘制角膜生物力学特性并生成能够预测治疗反应的患者特定计算模型。 基于模拟的优化将支持新型、可定制的扩张风险计算器和增强个体眼睛中胶原蛋白交联效果的新算法。 这些结果直接解决了 NEI 发现的差距，并将为现有和新兴的角膜手术提供新的基于模拟的治疗策略。