Enhanced backscattering instrument for assessing optical biomarkers of glaucoma

用于评估青光眼光学生物标志物的增强型反向散射仪器

基本信息

批准号：
9764362
负责人：
Gillian Jane McLellan
金额：
$ 18.49万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-15 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9764362
关键词：
Address Affect African Age American Animal Model Biological Markers Biomechanics Birefringence Blindness Cancer Biology Characteristics Clinical Collagen Computer Simulation Data Detection Development Diagnosis Diagnostic tests Dimensions Disease Disease Progression Early Diagnosis Early treatment Elderly Exhibits Extracellular Matrix Felis catus Fiber Foundations Generations Glaucoma Goals Human Individual Individual Differences Intervention Longitudinal Studies Measurement Measures Methods Microscopy Microspheres Modeling Nature Optic Disk Optics Patients Phase Physiologic Intraocular Pressure Play Population Predisposition Prognostic Marker Property Race Refractive Indices Research Personnel Resolution Risk Factors Role Sampling Sclera Screening for cancer Screening procedure Source Specimen Structure System Testing Time Tissue imaging Tissues Translations Visual impairment age related base cancer risk clinical application cost cost effective design experimental study imaging modality improved in vivo individualized medicine instrument light scattering models and simulation nanoscale nephelometry novel organizational structure potential biomarker pre-clinical precision medicine prognostic response screening second harmonic tool treatment planning

项目摘要

Project Summary: Glaucoma is a leading cause of irreversible blindness in the human population. Glaucoma is frequently associated with elevated intraocular pressure (IOP), but IOP alone is neither predictive of vision loss, nor the sole risk factor for disease progression, and its tendency to fluctuate over time makes it a suboptimal screening tool and prognostic indicator. The structural and biomechanical properties of the extracellular matrix, and in particular the collagen that makes up the sclera, have been widely implicated as playing a significant role in glaucoma susceptibility, though the precise nature of this relationship remains unresolved. Given the recognized influence of scleral properties on both IOP profile and optic nerve head deformation and damage in glaucoma, there is a critical need for non-invasive, cost-effective methods to quantify collagen microstructure in the sclera. Detection and quantification of optical scattering is sensitive to structural organization of tissue down to the nanoscale, well below the diffraction limited resolution of other imaging methods. Enhanced Backscattering (EBS) has been applied in a clinical setting to screen for cancer risk. We hypothesize that glaucoma-associated differences in scleral collagen structure can be quantified using EBS. However, EBS has not previously been applied to fibrous tissues like sclera, and assessment of scleral collagen structure will require development of new tissue-specific EBS approaches and hardware as well as new models for analyses. To overcome this barrier to clearer understanding of the role played by scleral collagen structure in glaucoma pathobiology, with the ultimate goal of developing a tool with translational potential, we propose two specific aims. In Aim 1: we will build the first polarimetric EBS instrument specifically optimized for sclera. This novel instrument will incorporate angular bandwidth matched to higher scattering by sclera and polarization control to provide sensitivity to birefringence of this fibrous tissue. The instrument will be validated using precision microsphere phantoms and applied in a unique animal model of glaucoma with acquisition of measurements from normal and glaucomatous sclera specimens ex vivo. In Aim 2: We will develop a computational model to relate EBS measurements to tissue collagen structure as determined by second harmonic generation microscopy, and based on scattering phase function from sclera using light scattering goniometry. The most significant differences in optical scattering signature between groups will be identified as a promising biomarker. Together, these experiments will provide a novel instrument and model with potential for translation to pre-clinical and clinical settings. In particular, the non-invasive nature of the test will permit much needed longitudinal studies of changes in collagen properties within individuals with spontaneous glaucoma, and also changes in response to age and interventions.

项目概要：青光眼是导致人类不可逆转失明的主要原因。青光眼经常与眼内压（IOP）升高有关，但 IOP 本身既不能预测视力丧失，也不能预测视力丧失。疾病进展的唯一危险因素，其随时间波动的趋势使其成为次优的筛查工具和预后指标。细胞外膜的结构和生物力学特性基质，特别是构成巩膜的胶原蛋白，已被广泛认为在发挥尽管这种关系的确切性质仍未解决，但在青光眼易感性中发挥着重要作用。鉴于巩膜特性对眼压分布和视神经乳头变形的公认影响和青光眼的损害，迫切需要非侵入性、具有成本效益的方法来量化巩膜中的胶原微结构。光学散射的检测和定量对以下因素很敏感组织的结构组织达到纳米级，远低于其他物质的衍射极限分辨率成像方法。增强型反向散射 (EBS) 已应用于临床筛查癌症风险。我们假设青光眼相关的巩膜胶原结构差异可以量化使用EBS。然而，EBS 之前尚未应用于巩膜等纤维组织，并且评估巩膜胶原结构将需要开发新的组织特异性 EBS 方法和硬件，如以及新的分析模型。为了克服这一障碍，更清楚地了解青光眼病理学中的巩膜胶原结构，最终目标是开发一种工具转化潜力，我们提出了两个具体目标。目标 1：我们将构建第一个偏振 EBS 专为巩膜优化的仪器。这种新颖的仪器将结合角带宽与巩膜和偏振控制的更高散射相匹配，以提供对双折射的敏感性纤维组织。该仪器将使用精密微球模型进行验证，并应用于独特的青光眼动物模型，获取正常和青光眼巩膜的测量结果离体标本。目标 2：我们将开发一个计算模型，将 EBS 测量与组织联系起来通过二次谐波发生显微镜测定并基于散射的胶原蛋白结构使用光散射测角法从巩膜获取相位函数。光学方面最显着的差异群体之间的散射特征将被认为是一种有前途的生物标志物。在一起，这些实验将提供一种新颖的仪器和模型，有可能转化为临床前和临床设置。特别是，该测试的非侵入性性质将允许进行急需的纵向研究自发性青光眼患者体内胶原蛋白特性的变化以及反应的变化年龄和干预措施。