Noninvasive 3D Microscopic Studies of Corneal Elasticity and Collagen Structure

角膜弹性和胶原蛋白结构的无创 3D 显微镜研究

• 批准号: 7527741
• 负责人: TIBOR JUHASZ
• 金额: $ 39.44万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7527741
• 关键词: 3-Dimensional; Acoustic Microscopy; Acoustics; Address; Affect; Astigmatism; Behavior; Biomechanics; Blindness; Cadaver; Cataract Extraction; Clinical; Clinical Data; Collagen; Condition; Cornea; Corneal Diseases; Data; Dependence; Development; Diagnosis; Disease; Disease Progression; Elasticity; Elements; Eye; Fourier Transform; Human; Human Characteristics; Image; Individual; Invasive; Keratoconus; Keratoplasty; Knowledge; Lasers; Lead; Left; Life; Localized; Maps; Measurement; Measures; Mechanics; Methods; Microscope; Microscopic; Microscopy; Modality; Modeling; Movement; Operative Surgical Procedures; Optics; Oryctolagus cuniculus; Outcome; Pathological Dilatation; Pattern; Physiologic pulse; Play; Postoperative Period; Procedures; Property; Public Health; Pulse taking; Radiation; Range; Resolution; Risk; Role; Spatial Distribution; Structure; Techniques; Technology; Testing; Therapeutic; Tissues; Transplantation; Variant; Vision; Visual; base; corneal surgery; improved; in vivo; instrument; novel; novel diagnostics; prevent; regional difference; research study; second harmonic; size; submicron; theories; tool; 3-Dimensional; Acoustic Microscopy; Acoustics; Address; Affect; Astigmatism; Behavior; Biomechanics; Blindness; Cadaver; Cataract Extraction; Clinical; Clinical Data; Collagen; Condition; Cornea; Corneal Diseases; Data; Dependence; Development; Diagnosis; Disease; Disease Progression; Elasticity; Elements; Eye; Fourier Transform; Human; Human Characteristics; Image; Individual; Invasive; Keratoconus; Keratoplasty; Knowledge; Lasers; Lead; Left; Life; Localized; Maps; Measurement; Measures; Mechanics; Methods; Microscope; Microscopic; Microscopy; Modality; Modeling; Movement; Operative Surgical Procedures; Optics; Oryctolagus cuniculus; Outcome; Pathological Dilatation; Pattern; Physiologic pulse; Play; Postoperative Period; Procedures; Property; Public Health; Pulse taking; Radiation; Range; Resolution; Risk; Role; Spatial Distribution; Structure; Techniques; Technology; Testing; Therapeutic; Tissues; Transplantation; Variant; Vision; Visual; base; corneal surgery; improved; in vivo; instrument; novel; novel diagnostics; prevent; regional difference; research study; second harmonic; size; submicron; theories; tool

DESCRIPTION (provided by applicant): Corneal biomechanics plays an important role in determining the eye's structural integrity, optical power and the overall quality of vision. Common conditions that manifest abnormal corneal biomechanics, such as keratoconus and post-LASIK ectasia affect millions of people and often necessitate corneal transplantation. Corneal biomechanics also plays an increasingly recognized role in the post-operative results of therapeutic and refractive corneal surgery procedures, affecting the predictability, quality and stability of final visual outcomes. A critical limitation to increasing our understanding of how corneal biomechanics controls corneal stability and refraction is the lack of non-invasive technologies that microscopically measure the corneal structure and local biomechanical properties, such as corneal elasticity within the 3D space. We hypothesize that by measuring the movement of a femtosecond laser generated cavitation bubble as it interacts with an acoustic radiation force, we can determine local values for an individual cornea's Young's modulus, without altering its structure and function. We also hypothesize that the inhomogeneous elastic properties of the cornea are strongly influenced by the microstructural organization of collagen lamellae, and that corneas with abnormal biomechanics also may be associated with an abnormal organization of corneal lamellae. Finally, we hypothesize that based on the elasticity and microstructural data for a particular cornea, a specific finite element model (FEM) can be constructed that accurately describes and predicts its biomechanical behavior. To test our hypothesis we plan to develop a bubble-based, acoustic radiation force elastic microscope (ARFEM) and show that it can be used noninvasively to develop a high resolution 3D corneal elasticity map. We will then correlate local variations in corneal elasticity with the microstructure observed by femtosecond laser based second harmonic imaging microscopy (SHIM). We will also investigate biomechanically disordered corneas with both, ARFEM and SHIM, and correlate their elasticity maps with microstructural observations. We will construct a FEM based on the measured ARFEM and SHIM data and show that this model accurately predicts biomechanical behavior for a particular cornea. Finally we will demonstrate in a live rabbit model, that both, ARFEM and SHIM can be performed safely in vivo without tissue damage or harmful effects to the eye. The successful completion of this project will provide experimental evidence that corneal elasticity maps and microstructure can be measured in vivo noninvasively. It will also provide support for the theory that corneal elasticity is influenced by the collagen microstructure, and that the biomechanical behavior of a cornea characterized by ARFEM and SHIM can be accurately predicted by individualized finite element modeling. The results of this project will increase our understanding of corneal biomechanics and its dependence on collagen microstructure and may provide the basis for a novel tool that could be helpful in diagnosing, preventing or treating increasingly common corneal diseases such as keratoconus and post-LASIK ectasia. PUBLIC HEALTH RELEVANCE: We introduce novel noninvasive methods to define spatial distribution of elastic properties and collagen microstructure of individual corneas. The correlation of these functional and structural measurements in healthy eyes will be compared with those that either have common corneal disorders (such as keratoconus and post-LASIK ectasia), or are at risk for them. The results of this project will improve our understanding of corneal biomechanics and its dependence on the collagen microstructure, providing a basis for novel diagnostic instruments and eventual therapeutic modalities for the millions of people that are at risk for severe visual loss from these conditions.

描述（由申请人提供）：角膜生物力学在确定眼睛的结构完整性，光学能力和整体视觉质量方面起着重要作用。表现出异常角膜生物力学的常见疾病，例如角膜结构和lasik后东南会影响数百万的人，并且通常需要角膜移植。角膜生物力学在治疗和屈光化角膜手术程序的术后结果中也起着越来越认识的作用，影响了最终视觉结果的可预测性，质量和稳定性。我们对角膜生物力学如何控制角膜稳定性和折射的理解的关键局限性是缺乏无创的技术，这些技术可以从显微镜上测量角膜结构和局部生物力学特性，例如3D空间内的角膜弹性。我们假设，通过测量飞秒激光与声学辐射力相互作用时产生的空化气泡的运动，我们可以确定单个角膜的幼体模量的局部值，而不会改变其结构和功能。我们还假设角膜的不均匀弹性特性受到胶原板片的微观结构组织的强烈影响，并且具有异常生物力学的角膜也可能与角膜薄片异常组织有关。最后，我们假设基于特定角膜的弹性和微观结构数据，可以构建特定的有限元模型（FEM），以准确描述和预测其生物力学行为。为了检验我们的假设，我们计划开发基于气泡的声学辐射力显微镜（ARFEM），并表明它可以无创用于开发高分辨率3D角膜弹性图。然后，我们将将角膜弹性的局部变化与基于飞秒激光的第二个谐波成像显微镜（SHIM）观察到的微观结构相关。我们还将与Arfem和Shim一起研究生物力学无序的角膜，并将其弹性图与微结构观测值相关联。我们将基于测得的ARFEM和SHIM数据构建FEM，并表明该模型准确地预测了特定角膜的生物力学行为。最后，我们将在活兔模型中证明，Arfem和Shim都可以在体内安全地进行，而无需组织损伤或对眼睛有害影响。该项目的成功完成将提供实验证据，表明角膜弹性图和微观结构可以非侵入性地测量。它还将为角膜弹性受胶原微观结构影响的理论提供支持，并且可以通过个性化有限元建模来准确预测的角膜的生物力学行为可以准确地预测。该项目的结果将增加我们对角膜生物力学及其对胶原蛋白微结构的依赖的理解，并可能为一种新颖的工具提供基础，该工具可能有助于诊断，防止或治疗越来越常见的角膜疾病，例如角膜生角膜细胞和lasasik ectasia。公共卫生相关性：我们引入了新型的无创方法来定义弹性特性和单个角膜胶原微观结构的空间分布。将这些功能和结构测量在健康眼中的相关性将与患有常见的角膜疾病（例如角膜结构和Lasik ectasia）或有风险的常见角膜疾病进行比较。该项目的结果将提高我们对角膜生物力学及其对胶原蛋白微观结构的依赖的理解，为数百万危险从这些状况严重视觉损失风险的人提供新颖的诊断仪器和最终治疗方式的基础。