Coherent light scattering for early detection of retinal disease

相干光散射用于早期检测视网膜疾病

• 批准号: 8512962
• 负责人: Adam Wax
• 金额: $ 22.72万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8512962
• 关键词: Animal Model; Animals; Barrett Esophagus; Biological Markers; Cell Nucleus; Cells; Cellular Structures; Characteristics; Clinical; Data; Degenerative Disorder; Detection; Development; Devices; Diagnosis; Diagnostic; Disease; Disease Progression; Dysplasia in Barrett' s Esophagus; Early Diagnosis; Epithelial Cells; Epithelium; Esophageal; Eye; Future; Glaucoma; Goals; Health; Human; Image; Imaging Techniques; Imaging technology; Individual; Interferometry; Knock-out; Life; Measurement; Measures; Methods; Metric; Modality; Modeling; Morphology; Mus; Nerve Degeneration; Normal tissue morphology; Nuclear; Ocular Pathology; Ophthalmoscopes; Optical Coherence Tomography; Optics; Organizational Change; Pathology; Patients; Pharmaceutical Preparations; Photoreceptors; Premalignant Cell; Public Health; Research; Resolution; Retina; Retinal; Retinal Cone; Retinal Degeneration; Retinal Diseases; Retinitis Pigmentosa; Rhodopsin; Scanning; Staging; Structure; System; Techniques; Technology; Thick; Time; Tissues; Treatment Efficacy; Visual system structure; adaptive optics; base; clinical application; density; design; improved; in vivo; light scattering; meetings; novel; optical imaging; portability; prototype; public health relevance; research study; retinal nerve fiber layer; retinal neuron; retinal rods; screening

DESCRIPTION (provided by applicant): The overall objective of this proposal is to develop a novel in vivo optical imaging system that will quantify structural biomarkers of retinal degenerative diseases. The state-of-the-art technology is measurement of the thickness of retina layers by spectral domain optical coherence tomography (SDOCT). However, while SDOCT can resolve histological layers, it lacks the resolution to measure cellular features. In recent SDOCT studies, only a modest correlation between the thickness of the retinal nerve fiber layer and the progression of glaucoma has been shown, with similar findings seen between the thickness of the photoreceptor layer and progression of retinitis pigmentosa. This reflects the fact that thickness of an individual retina layer does not necessarily correlate with the healt or anatomical condition of its constituent cells. We have shown that angle-resolved low coherence interferometry (a/LCI), a light scattering method that incorporates the depth resolution of OCT, can acquire depth-resolved morphological measurements of esophageal epithelial cells, which allows in vivo early detection of dysplasia in Barrett's Esophagus patients Unlike other non-invasive imaging techniques, a/LCI allows direct and specific measurements of the nuclear morphology of epithelial cells within intact, unstained tissues. We have shown that a/LCI can detect changes in organization of cells in the retinal layer due to pathology. We now propose to apply a/LCI to the diagnosis of ocular diseases by developing an a/LCI imaging system that is compatible with a scanning ophthalmoscope in order to execute depth-resolved measurements of the nuclear morphology of retinal neurons. Here we will seek to formulate accurate quantitative biomarkers that predict the onset and progression of neurodegenerative ocular pathologies based on these structural and organizational changes. In this project, (1) we will implement a prototype a/LCI system to enable in vivo studies of the retina and (2) apply the system to a detailed time course study of a murine model of progressive retinal degeneration to characterize the changes in both size and organization of photoreceptor structures as a function of disease progression. Upon successful completion of this exploratory research study, there will be justification to pursue development of a clinical a/LCI device for application to humans.

描述（由申请人提供）：该提案的总体目标是开发一种新型的体内光学成像系统，该系统将量化视网膜退行性疾病的结构生物标志物。最先进的技术是通过光谱域光学相干断层扫描（SDOCT）对视网膜层的厚度进行测量。但是，尽管SDOCT可以解决组织学层，但缺乏测量细胞特征的分辨率。在最近的SDOCT研究中，已经显示出视网膜神经纤维层的厚度与青光眼的进展之间仅存在适度的相关性，在感光体层的厚度与色素炎的进展之间存在相似的发现。这反映了一个事实，即单个视网膜层的厚度不一定与其组成细胞的愈合或解剖状态相关。我们已经表明，角度分辨的低相干干涉法（A/LCI）是一种融合了OCT深度分辨率的光散射方法，可以获取深度分辨的食管上皮细胞的深度分辨形态测量，从而可以在Barrett的体内早期检测到Barrett dospplasia in Barrett的体内检测食道患者与其他非侵入性成像技术不同，A/LCI允许对完整，未染色的组织中上皮细胞的核形态进行直接和特定的测量。我们已经表明，由于病理学，A/LCI可以检测视网膜层中细胞组织的变化。现在，我们建议通过开发与扫描眼镜兼容的A/LCI成像系统来诊断眼部疾病的A/LCI，以执行视网膜神经元核形态的深度分辨测量。在这里，我们将寻求制定准确的定量生物标志物，以预测基于这些结构和组织变化的神经退行性眼病理的发作和进展。在该项目中，（1）我们将实施一个原型A/LCI系统来实现视网膜的体内研究，（2）将系统应用于渐进视网膜变性的鼠模型的详细时间课程，以表征变化光感受器结构的大小和组织是疾病进展的函数。成功完成这项探索性研究后，将有合理的理由来开发临床A/LCI设备以应用于人类。