Development and Validation of Photothermal Optical Coherence Tomography for Retinal Imaging

用于视网膜成像的光热光学相干断层扫描的开发和验证

• 批准号: 10380391
• 负责人: Melissa Caroline Skala
• 金额: $ 23.22万
• 依托单位: MORGRIDGE INSTITUTE FOR RESEARCH, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10380391
• 关键词: 3-Dimensional; Adult; Affect; Age related macular degeneration; Aging; Albinism; American; Animal Model; Atrophic; Blindness; Calibration; Choroid; Cytoplasmic Granules; Data; Defect; Development; Disease; Disease Marker; Disease Progression; Drusen; Epithelial Cells; Eye; Functional disorder; Goals; Health; Histology; Human; Hyperpigmentation; Hypopigmentation; Image; Imaging Techniques; Impairment; Institutes; Iris; Light; Location; Measurement; Measures; Melanins; Methods; Microscopy; Modeling; Monitor; Mus; Nonexudative age-related macular degeneration; Ocular Albinism; Oculocutaneous Albinism; Optical Coherence Tomography; Optics; Pathology; Patients; Photoreceptors; Pigmentation physiologic function; Pigments; Play; Pre-Clinical Model; Reactive Oxygen Species; Reproducibility; Resolution; Retina; Retinal Diseases; Risk; Role; Safety; Sampling; Signal Transduction; Specificity; Stargardt' s disease; Structure; Structure of retinal pigment epithelium; Techniques; Technology; Testing; Three-Dimensional Image; Three-Dimensional Imaging; Time; Tissues; Treatment Efficacy; Validation; Vision; Visual; Visual Acuity; Visual system structure; Zebrafish; clinical application; clinical diagnosis; clinical imaging; drug development; experimental study; first-in-human; geographic atrophy; human imaging; human old age (65+); in vivo; in vivo imaging; novel therapeutics; phantom model; pre-clinical; prevent; retinal imaging

PROJECT SUMMARY Melanin is naturally present in the eye within the choroid, iris, and retinal pigment epithelium (RPE), a single layer of epithelial cells located posterior to the photoreceptors in the retina. Changes in retinal pigmentation normally happen with aging and are present in many ocular diseases. For example, age-related macular degeneration (AMD) is the predominant cause of vision loss in adults over 65 years old in the US and involves dysfunction of the RPE and changes in pigmentation. In early stages, AMD is usually characterized by changes in pigmentation and the presence of drusen. In dry AMD, data suggest that hyperpigmentation in the RPE (from dysfunction in the RPE cells) followed by hypopigmentation (from the loss of RPE cells) appear before dysfunction in the photoreceptors or choriocapillaris and could be predictive for disease progression. Management of retinal diseases requires robust methods to quantify retinal melanin, specifically in the RPE. However, current techniques to image retinal melanin have limitations that prevent 3D in vivo imaging of melanin levels in the eye. For example, near-infrared autofluorescence and photoacoustic microscopy suffer from poor axial resolution that cannot resolve the RPE with respect to other structures, while polarization-sensitive optical coherence tomography has difficulty recovering accurate melanin levels due to scattering of pigment granules and a narrow dynamic range. As a result, there are currently no standard in vivo techniques to quantify melanin levels in the eye. Given the potential for melanin as an early disease marker, there is a great need for an ophthalmic imaging technique to quantify melanin levels in patients and animal models. The goal of this proposal is to develop photothermal optical coherence tomography (PT-OCT) to image and quantify melanin levels in the living human eye. PT-OCT detects optical absorbers in tissues, with similar resolution and imaging depth as OCT. The PT-OCT signal intensity is proportional to the concentration of the absorber (e.g., melanin), which allows for quantitative 3D images of melanin concentration. We have shown that PT-OCT can specifically measure melanin in the RPE of mouse and zebrafish models. Importantly, light exposure levels for PT-OCT in the eye are within safety standards and the FDA recently designated PT-OCT in the eye as a non-significant risk study. PT-OCT is advantageous for melanin imaging in the RPE because it is sensitive to small changes in pigmentation and the photothermal signal is easily quantified for robust comparisons between samples. This proposal aims to determine PT-OCT melanin sensitivity ranges and first- in-human feasibility to enable quantitative 3D imaging of melanin in the eye in vivo.

项目摘要 黑色素自然存在于脉络膜，虹膜和视网膜色素上皮（RPE）内的眼睛中 位于视网膜中光感受器后部的上皮细胞层。视网膜色素沉着的变化 通常发生在衰老中，并且存在于许多眼部疾病中。例如，与年龄相关的黄斑 退化（AMD）是美国65岁以上成人视力丧失的主要原因，涉及 RPE功能障碍和色素沉着的变化。在早期，AMD通常以变化为特征 在色素沉着和drusen的存在中。在干燥的AMD中，数据表明RPE的色素沉着过度（来自 RPE细胞中功能障碍）随后出现不形成（来自RPE细胞的损失） 光感受器或绒毛膜毛细血管的功能障碍，可以预测疾病进展。 视网膜疾病的治疗需要可靠的方法来量化视网膜黑色素，特别是在RPE中。 但是，当前的图像视网膜黑色素的技术具有防止黑色素体内成像3D的局限性 眼中的水平。例如，近红外自动荧光和光声显微镜的障碍 轴向分辨率无法解决其他结构，而对极化敏感的光学 由于色素颗粒的散射，相干断层扫描难以恢复准确的黑色素水平 和狭窄的动态范围。结果，目前尚无标准体内技术来量化黑色素 眼中的水平。鉴于黑色素作为早期疾病标记的潜力，很需要 眼科成像技术可量化患者和动物模型的黑色素水平。 该建议的目的是将光热光学相干断层扫描（PT-OCT）开发为图像和图像 量化活着的人眼中黑色素水平。 PT-OCT检测组织中的光吸收器 分辨率和成像深度为OCT。 PT-OCT信号强度与浓度成正比 吸收剂（例如黑色素），它允许黑色素浓度的定量3D图像。我们已经表明 PT-OCT可以在小鼠和斑马鱼模型的RPE中特异性测量黑色素。重要的是，光 眼睛中PT-OCT的暴露水平在安全标准范围内，FDA最近指定为PT-OCT 眼睛是一项不重要的风险研究。 PT-OCT对于RPE中的黑色素成像是有利的，因为它是 对色素沉着的小变化敏感和光热信号很容易量化以实现鲁棒 样品之间的比较。该建议旨在确定PT-OCT黑色素敏感性范围和首先 内人类的可行性，可以在体内对黑色素的定量3D成像。