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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：青光眼是人类群体中不可逆失明的主要原因。青光眼是常见的与眼内压（IOP）升高相关，但单独IOP既不能预测视力丧失，疾病进展的唯一风险因素，其随时间波动的趋势使其成为次优筛选工具和预后指标。细胞外基质的结构和生物力学特性基质，特别是构成巩膜的胶原蛋白，已经被广泛地暗示为起作用，在青光眼易感性中起重要作用，尽管这种关系的确切性质尚未得到解决。鉴于巩膜特性对IOP曲线和视神经乳头变形的影响已得到公认，和损害的青光眼，有一个非侵入性的，具有成本效益的方法来量化的迫切需要巩膜中的胶原微结构。光学散射的检测和定量对以下因素敏感：组织的结构组织下降到纳米级，远低于其他衍射极限分辨率成像方法增强后向散射（EBS）已应用于临床环境中筛选癌症风险我们假设可以量化与青光眼相关的巩膜胶原结构差异使用EBS。然而，EBS先前尚未应用于纤维组织如巩膜，并且评估其对视网膜的影响。巩膜胶原结构将需要开发新的组织特异性EBS方法和硬件，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，翻译潜力，我们提出了两个具体的目标。在目标1中：我们将建立第一个极化EBS 专门为巩膜优化的仪器。这种新颖的仪器将纳入角带宽与巩膜的更高散射和偏振控制相匹配，以提供对这种双折射的灵敏度。纤维组织该仪器将使用精密微球体模进行验证，并应用于一种独特的青光眼动物模型，其测量值来自正常和青光眼巩膜离体标本。目标2：我们将开发一个计算模型，将EBS测量与组织通过二次谐波发生显微镜测定的胶原结构，并基于散射使用光散射测角术从巩膜获得相位函数。最显著的差异在光学组之间的散射特征将被鉴定为有希望的生物标志物。所有这些实验将提供一种新的仪器和模型，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非常需要的纵向研究，自发性青光眼患者体内胶原性质的变化，以及对年龄和干预。