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