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）：角膜扩散是美国与视觉相关的生活质量受损的主要原因，也是角膜移植的主要指标。 缺乏解决整个角膜生物力学特性的临床工具，这是了解角膜不稳定性机制的关键障碍，并应用潜在的变革性生物工程方法来进行风险筛查和治疗优化。 该研究计划的目的是开发一个基于OCT的强大仿真平台，以量化东南风险并预测对广泛角膜治疗的个人反应。 该目标得到了角膜形状和视觉功能之间的敏感联系，是通过综合患者特定于患者特定的生物力学测量和建模来确定脑疾病的关键结构预测指标，并开发出定制的交联治疗方法。 中心假设是角膜中生物力学特性的大小和分布是角膜形状的关键驱动因素。 该假设和测试方法的部分是通过申请人在角膜光学相干弹性学（OCE）和患者特异性有限元（FE）分析研究中的初步工作进行了开发的，这些研究建议材料特性和形状之间的重要依赖性。 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使用特定于患者的模拟进行交联反应。 在AIM 1下，OCE将用于供体眼和临床研究中，以测试人角膜在生物力学特性上具有内在的区域差异的假设，这些特性在Lasik，oeratoconus和胶原蛋白交叉链接中以特征性的方式改变了生物力学性质。 在AIM 1中使用主题特定的几何形状生成FE模型后，AIM 2将检验以下假设：与具有理想化的散装属性估计值的模型相比，用主题特定的OCE特性数据填充的模型更好地预测结果。 最后，在大规模的多因素Fe模拟中，使用Al正常患者和角膜生角患者作为建模，AIM 3将确定弹性特性，初始角膜几何和过程变量如何相互作用以影响ectasia危险和 交联反应。 预期的结果包括基于OCT的能力的临床翻译，用于绘制角膜生物力学特性，并产生能够预测治疗反应的患者特异性计算模型。 基于仿真的优化将支持新颖的，可自定义的计算器，以实现ectasia风险和新算法，以增强单个眼睛中胶原蛋白交联的影响。 这些结果直接解决了NEI确定的差距，并将为现有和新兴的角膜程序提供新的基于模拟的治疗策略。