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.

本提案旨在发展新一代扫频光源光学相干层析成像技术（SS-OCT） 在530- 600 nm附近的可见光波长下工作的技术，用于视网膜成像和血氧测定。这项工作将 开发第一个可见光波长范围内的扫频光源和SS-OCT系统， 与当前可见光谱域OCT（SD-OCT）系统相比， 超连续谱激光源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，以实现波长扫近的宽可调谐二次谐波产生 微机电系统的红外激光发射垂直腔面发射激光器 （MEMS-VCSEL），部分在先前NIH赠款R44 EY 022864和R44 CA 101067下开发。组合NIR 采用先进PPLN波导技术的MEMS-VCSEL将创造高性能、体积可扩展的 用于OCT技术的可见扫频光源。这项为期2.5年的快速SBIR工作的八个具体目标可以是 大致分为扫频源开发目标、SS-OCT开发和成像目标，如下所述。扫 源开发目标。Praevium将开发调谐范围> 70 nm全波长扫频光源 半高宽（FWHM）和峰值功率> 8 mW（平均功率约3 mW），重叠高对比度和 在530- 600 nm范围内的等吸光度血氧测定波长。Praevium将开发新的PPLN波导设计 和制造技术，实现了在1060- 1060 nm附近的新波长范围内的MEMS-VCSEL的记录调谐范围。 1200 nm，开发与新型MEMS-VCSEL相匹配的高功率宽带半导体光放大器 波长我们的工作将通过三个扫频源代（GEN 1，GEN 2，GEN 3）进行， 以下最小FWHM扫描范围/峰值功率：GEN 1：20 nm/1 mW，GEN 2：40 nm/5 mW，GEN 3： 70nm/8mW。SS-OCT系统开发和成像目标。麻省理工学院的合作者将评估MEMS- VCSEL+PPLN来自Praevium，并开发用于人类视网膜成像的可见SS-OCT技术。双 将使用平衡检测来增加外差增益和灵敏度，并进行逐扫描校准 使用OCT和校准信号的双通道采集， 长成像距离。这些进步有望实现~ 400 kHz的A扫描速率，比现有的快~5-10倍 可见SD-OCT。麻省理工学院的合作者将开发分析框架来计算血氧饱和度， 从可见光SD-OCT中提炼血氧测量方法。更高的速度和灵敏度有望使视网膜 毛细血管血氧测定法和使用可见SS-OCT血管造影术估计相对血流速度。最后，工作 与正在进行的NIH项目R 01 EY 011289的临床合作者一起，麻省理工学院的合作者将进行可见的SS- 在正常受试者和糖尿病视网膜病变患者队列中进行OCT研究，以研究结构和 使用OCT、OCTA和视网膜血氧测定法的功能性生物标志物。本研究将评估其可行性和临床 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。