Swept source retinal visible optical coherence tomography using broadly tunable frequency doubling of NIR MEMS-VCSELs

使用近红外 MEMS-VCSEL 的宽可调倍频进行扫描源视网膜可见光学相干断层扫描

• 批准号: 10546927
• 负责人: Vijaysekhar Jayaraman
• 金额: $ 37万
• 依托单位: PRAEVIUM 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: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10546927
• 关键词: 3-Dimensional; Age related macular degeneration; Air; Amplifiers; Angiography; Biological Markers; Blood; Blood capillaries; Blood flow; Calibration; Clinical; Clinical Research; Detection; Development; Diabetic Retinopathy; Disease; Early Diagnosis; Engineering; Eye; Frequencies; Functional Imaging; Future; Generations; Glaucoma; Grant; Hemoglobin; Human; Image; Imaging technology; Indium; Institutes; Investigation; Lasers; Length; Light; Massachusetts; Measurement; Methods; Microscope; Monitor; Noise; Optical Coherence Tomography; Optics; Oxygen; Oxygen saturation measurement; Oxyhemoglobin; Pathogenesis; Patients; Performance; Phase; Research; Resolution; Retina; Retinal Diseases; Scanning; Semiconductors; Shapes; Signal Transduction; Small Business Innovation Research Grant; Source; Speed; Surface; System; Systems Development; Technology; Testing; United States National Institutes of Health; Visualization; Width; Work; absorption; cohort; design; diabetic; fundamental research; gallium arsenide; heterodyning; imaging study; improved; innovation; instrument; lithium niobate; multidisciplinary; next generation; novel; operation; programs; retinal imaging; second harmonic; waveguide

This proposal aims to develop a new generation of swept source optical coherence tomography (SS-OCT) technology operating at visible wavelengths near 530-600nm for retinal imaging and oximetry. This work will develop the first swept sources and SS-OCT systems in the visible wavelength range, enabling increased sensitivity, imaging range and speed compared to current visible spectral domain OCT (SD-OCT) systems with supercontinuum laser sources. Our approach uses novel dispersion engineered, periodically poled Lithium Niobate (PPLN) waveguides to achieve broadly tunable second harmonic generation of wavelength swept near infrared (NIR) laser emission from micro-electro-mechanical systems vertical cavity surface emitting lasers (MEMS-VCSELs), developed in part under prior NIH grants R44EY022864 and R44CA101067. Combining NIR MEMS-VCSELs with advanced PPLN waveguide technology will create a high performance, volume scalable visible swept source for OCT technology. The eight specific aims of this 2.5 year fast track SBIR effort can be broadly divided into swept source development aims, SS-OCT development and imaging aims as follows. Swept source development aims. Praevium will develop a wavelength swept source having a tuning range >70nm full width at half maximum (FWHM) and peak power >8mW (average power ~3mW), overlapping high contrast and isosbestic oximetry wavelengths in the 530-600nm range. Praevium will develop new PPLN waveguide designs and fabrication technology, achieve record tuning range MEMS-VCSELs in a new wavelength range near 1060- 1200nm and develop high power broadband semiconductor optical amplifiers matching the new MEMS-VCSEL wavelength. Our work will progress through three swept source generations (GEN1, GEN2, GEN3) having the following minimum FWHM sweep range/peak power: GEN1: 20nm/1mW, GEN2: 40nm/5mW, and GEN3: 70nm/8mW. SS-OCT system development and imaging aims. MIT collaborators will evaluate MEMS- VCSEL+PPLN sources from Praevium and develop visible SS-OCT technology for human retinal imaging. Dual balanced detection will be used to increase heterodyne gain and sensitivity, with sweep-by-sweep calibration using two channel acquisition of OCT and calibration signals to achieve uniform sensitivity and resolution over long imaging ranges. These advances promise to achieve A-scan rates of ~400kHz, ~5-10× faster than existing visible SD-OCT. MIT collaborators will develop analytical frameworks to compute blood oxygen saturation by refining oximetry methods from visible SD-OCT. Higher speeds and sensitivities promise to enable retinal capillary oximetry and estimating relative blood flow speeds using visible SS-OCT angiography. Finally, working with clinical collaborators in an ongoing NIH program R01EY011289, MIT collaborators will perform visible SS- OCT studies in a cohort of normal subjects and patients with diabetic retinopathy to investigate structural and functional biomarkers using OCT, OCTA and retinal oximetry. This study will assess the feasibility and clinical workflow of visible SS-OCT imaging and determine potential future clinical and research applications.

该提案旨在开发新一代扫频源光学相干断层扫描（SS-OCT） 这项工作将在 530-600nm 附近的可见波长下运行，用于视网膜成像和血氧测定。 开发第一个可见光波长范围内的扫频光源和 SS-OCT 系统，能够提高 与当前的可见光谱域 OCT (SD-OCT) 系统相比，其灵敏度、成像范围和速度 我们的方法使用新型色散工程、周期性极化锂。 铌酸盐（PPLN）波导可实现近扫波长的宽范围可调谐二次谐波 微机电系统的红外 (NIR) 激光发射垂直腔表面发射激光器 （MEMS-VCSEL），部分是根据 NIH 先前拨款 R44EY022864 和 R44CA101067 结合 NIR 开发的。 具有先进 PPLN 波导技术的 MEMS-VCSEL 将创造出高性能、体积可扩展的 OCT 技术的可见扫频源可以是 2.5 年快速轨道 SBIR 工作的八个具体目标。 大致分为扫频源开发目标、SS-OCT 开发和扫频成像目标。 Praevium 将开发调谐范围 >70nm 的波长扫频光源。 半高宽 (FWHM) 和峰值功率 >8mW（平均功率 ~3mW），重叠高对比度和 530-600nm 范围内的等吸血氧测定波长 Praevium 将开发新的 PPLN 波导设计。 和制造技术，在接近 1060 的新波长范围内实现创纪录的 MEMS-VCSEL 调谐范围 1200nm并开发匹配新型MEMS-VCSEL的高功率宽带半导体光放大器 我们的工作将通过三代扫频光源（GEN1、GEN2、GEN3）取得进展。 以下最小 FWHM 扫描范围/峰值功率：GEN1：20nm/1mW、GEN2：40nm/5mW 和 GEN3： 70nm/8mW。 SS-OCT 系统开发和成像目标将评估 MEMS-。 VCSEL+PPLN 源自 Praevium 并开发用于人类视网膜双成像的可见 SS-OCT 技术。 平衡检测将用于增加外差增益和灵敏度，并进行逐次扫描校准 使用 OCT 和校准信号的两个通道采集来实现统一的灵敏度和分辨率 这些进步有望实现约 400kHz 的 A 扫描速率，比现有技术快约 5-10 倍。 可见的 SD-OCT 合作者将开发分析框架来计算血氧饱和度 从可见光 SD-OCT 中改进血氧测定方法，有望实现视网膜成像。 毛细血管血氧测定法并使用可见 SS-OCT 血管造影估计相对血流速度最后，开始工作。 麻省理工学院的合作者将与正在进行的 NIH 项目 R01EY011289 中的临床合作者一起执行可见的 SS- 在一组正常受试者和糖尿病视网膜病变患者中进行 OCT 研究，以研究结构和 这项研究将评估使用 OCT、OCTA 和视网膜血氧测定法的功能生物标志物的可行性和临床效果。 可见 SS-OCT 成像的工作流程，并确定未来潜在的临床和研究应用。