True Sub-Micron Ocular Diagnostics with Visible Light Optical Coherence Tomography

使用可见光光学相干断层扫描进行真正的亚微米眼部诊断

• 批准号: 10676879
• 负责人: Vivek Jay Srinivasan
• 金额: $ 50.5万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10676879
• 关键词: Accounting; Age; Age related macular degeneration; Aging; Anatomy; Atrophic; Benchmarking; Biological Markers; Blindness; Bruch' s basal membrane structure; Classification; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Communities; Complex; Cone; Data; Densitometry; Deposition; Diagnosis; Diagnostic; Drusen; Elderly; Ethnic Origin; Eye; Fiber; Fundus; Goals; Histopathology; Human; Image; Imaging technology; In Vitro; Individual; Intervention Trial; Light; Longitudinal Studies; Macular degeneration; Maps; Measurement; Measures; Melanins; Melanosomes; Modality; Modeling; Molecular; Morphology; Mus; Non-Invasive Detection; Nonexudative age-related macular degeneration; Optical Coherence Tomography; Optics; Pathology; Photoreceptors; Pigmentation physiologic function; Protocols documentation; Reproducibility; Resolution; Rest; Retina; Retinal Diseases; Risk Factors; Rodent; Scanning; Sensitivity and Specificity; Severities; Shapes; Specificity; Structure of retinal pigment epithelium; System; Technology; Testing; Thick; Time; Validation; Visible Radiation; Vision; Visualization; Work; adaptive optics; age related; attenuation; biomarker identification; candidate identification; candidate marker; chromophore; clinical imaging; cohort; data acquisition; density; early detection biomarkers; effective therapy; end stage disease; experimental study; geographic atrophy; imaging capabilities; imaging study; improved; in vivo; in vivo imaging; innovation; instrument; instrumentation; morphometry; new technology; predictive marker; progression marker; progression risk; retinal imaging; specific biomarkers; structural imaging; submicron; ultra high resolution

Abstract: Optical Coherence Tomography (OCT) has greatly advanced the diagnosis and management of many retinal diseases by enabling volumetric structural imaging of the retina. Usually, retinal OCT is performed at near- infrared (NIR) wavelengths, limiting both axial resolution and contrast for molecules that play a role in vision. Though NIR OCT defines biomarkers that quantify progression of dry age-related macular degeneration (AMD), NIR OCT cannot yet delineate the finest structural and functional changes that define incipient AMD, or predict geographic atrophy, an end stage of AMD. Visible light OCT holds the promise of unprecedented axial resolution and molecular contrast, but visible light OCT systems to date have not delivered on this promise. Recently, our group identified numerous technical barriers, some unknown to the community, in visible light OCT. With our innovative solutions, we can now directly image and individually quantify Bruch’s membrane, the retinal pigment epithelium (RPE), and fine photoreceptor layers in morphologically normal retina without clinically detectable pathology, at a level of detail not attained by NIR OCT systems. These imaging capabilities are further enhanced by quantitative molecular information provided by visible light. In this proposal, we will develop fiber-based visible light OCT instrumentation and protocols to assess sub-micron changes with aging and macular degeneration in human eyes. Employing a range of in vitro and in vivo studies in rodents and humans, we propose to validate protocols that topographically measure the outer retina, RPE, and BM morphology, photopigment and melanin density, and photoreceptor function. We will validate and test the reproducibility of these structural and functional measurements, and apply them to study age-related changes in a cross-section of normal subjects. Finally, we will perform pilot clinical imaging studies to firstly, compare aging to early AMD, and secondly, identify candidate early biomarkers for progression of drusen to atrophy. If successful, this proposal will lay the groundwork for more extended longitudinal studies to study AMD progression in the human retina, and incorporation of new biomarkers into clinical trials.

抽象的： 光学相干断层扫描 (OCT) 极大地推进了许多视网膜疾病的诊断和管理 通常，视网膜 OCT 是在近端进行的。 红外 (NIR) 波长，限制了在视觉中发挥作用的分子的轴向分辨率和对比度。 尽管 NIR OCT 定义了量化干性年龄相关性黄斑变性 (AMD) 进展的生物标志物， NIR OCT 尚无法描述定义早期 AMD 或预测的最精细的结构和功能变化 地理萎缩是 AMD 的末期阶段，可见光 OCT 有望实现前所未有的轴向分辨率。 和分子对比，但迄今为止可见光 OCT 系统尚未兑现这一承诺。 最近，我们的团队在可见光 OCT 中发现了许多技术障碍，其中一些是业界未知的。 借助我们的创新解决方案，我们现在可以直接成像并单独量化布鲁赫膜（视网膜） 色素上皮 (RPE) 和形态正常的视网膜中的精细感光层，无临床症状 近红外 OCT 系统无法达到可检测的病理细节。 可见光提供的定量分子信息进一步增强。 在本提案中，我们将开发基于光纤的可见光 OCT 仪器和协议来评估亚微米 采用一系列体外和体内研究来研究人眼随衰老和黄斑变性而发生的变化。 在啮齿动物和人类中，我们建议验证从地形上测量外视网膜、RPE、 我们将验证和测试 BM 形态、感光色素和黑色素密度以及感光器功能。 这些结构和功能测量的可重复性，并将其应用于研究与年龄相关的变化 最后，我们将进行试点临床影像研究，首先进行比较。 其次，确定玻璃疣进展为萎缩的候选早期生物标志物。 成功后，该提案将为更广泛的 AMD 纵向研究奠定基础 在人类视网膜中，以及将新的生物标志物纳入临床试验的进展。

项目成果

Multi-exposure interferometric diffusing wave spectroscopy.

• DOI: 10.1364/ol.427746
• 发表时间: 2021-09-15
• 期刊: OPTICS LETTERS
• 影响因子: 3.6
• 作者: Zhou, Wenjun;Zhao, Mingjun;Kholiqov, Oybek;Srinivasan, Vivek J.
• 通讯作者: Srinivasan, Vivek J.

1700 nm optical coherence microscopy enables minimally invasive, label-free, in vivo optical biopsy deep in the mouse brain.

• DOI: 10.1038/s41377-021-00586-7
• 发表时间: 2021-07-14
• 期刊: Light, science & applications
• 作者: Zhu J;Freitas HR;Maezawa I;Jin LW;Srinivasan VJ
• 通讯作者: Srinivasan VJ

Visible Light Optical Coherence Tomography (OCT) Quantifies Subcellular Contributions to Outer Retinal Band 4.

• DOI: 10.1167/tvst.10.3.30
• 发表时间: 2021-03-01
• 期刊: Translational vision science & technology
• 影响因子: 3
• 作者: Zhang T;Kho AM;Yiu G;Srinivasan VJ
• 通讯作者: Srinivasan VJ

Incoherent excess noise spectrally encodes broadband light sources.

• DOI: 10.1038/s41377-020-00404-6
• 发表时间: 2020
• 期刊: Light, science & applications
• 作者: Kho AM;Zhang T;Zhu J;Merkle CW;Srinivasan VJ
• 通讯作者: Srinivasan VJ

Scanning interferometric near-infrared spectroscopy.

• DOI: 10.1364/ol.443533
• 发表时间: 2022-01-01
• 期刊: OPTICS LETTERS
• 影响因子: 3.6
• 作者: Kholiqov, Oybek;Zhou, Wenjun;Zhang, Tingwei;Zhao, Mingjun;Ghandiparsi, Soroush;Srinivasan, Vivek J.
• 通讯作者: Srinivasan, Vivek J.