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颖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谱域光学相干断层扫描（SDOCT）测量视网膜层的厚度。然而，虽然 SDOCT 可以解析组织学层，但它缺乏测量细胞特征的分辨率。在最近的 SDOCT 研究中，仅显示视网膜神经纤维层的厚度与青光眼的进展之间存在适度的相关性，感光层的厚度与色素性视网膜炎的进展之间也有类似的发现。这反映了这样一个事实：单个视网膜层的厚度不一定与其组成细胞的健康或解剖状况相关。我们已经证明，角度分辨低相干干涉测量法（a/LCI）是一种结合了 OCT 深度分辨率的光散射方法，可以获得食管上皮细胞的深度分辨形态学测量，从而可以在体内早期检测巴雷特氏病的发育不良。食道患者与其他非侵入性成像技术不同，a/LCI 可以直接、特异性地测量完整、未染色组织内上皮细胞的核形态。我们已经证明，a/LCI 可以检测由于病理原因导致的视网膜层细胞组织的变化。我们现在建议通过开发与扫描检眼镜兼容的a/LCI成像系统，将a/LCI应用于眼部疾病的诊断，以便对视网膜神经元的核形态进行深度分辨测量。在这里，我们将寻求制定准确的定量生物标志物，根据这些结构和组织的变化来预测神经退行性眼部病变的发生和进展。在这个项目中，（1）我们将实现一个原型 a/LCI 系统，以实现视网膜的体内研究，（2）将该系统应用于进行性视网膜变性小鼠模型的详细时间过程研究，以表征视网膜的变化。光感受器结构的大小和组织作为疾病进展的函数。成功完成这项探索性研究后，就有理由继续开发应用于人类的临床 a/LCI 设备。