Non-Invasive Oxygenation Measurement in Retinal Blood Vessel Phantoms Using Spectroscopic Pump-Probe Phase-Sensitive Oct

Abstract

Purpose: : Because the retina requires an uninterrupted oxygen supply, retinal hypoxia is a possible trigger of many retinal pathologies including diabetic retinopathy (DR) and glaucoma. Disease-induced changes, such as tissue oxygenation, often precede structural abnormalities associated with retinal pathologies and thus tissue oxygen could serve as an early biomarker of disease onset. We present a proof-of-concept study using spectroscopic pump-probe Phase-Sensitive OCT (PhS OCT) and retinal blood vessel phantoms to measure oxygenation (SO2). The long-term goal is to enable oxygenation tension measurement with laminar resolution in the human retinas.

Methods: : We combine an ultra-sensitive PhS-OCT system with pump-probe spectroscopy to measure blood oxygenation levels in phantom retinal blood vessels. Picometer phase sensitivity allows detection thermoelastic expansion of the walls of phantom retinal blood vessels due to hemoglobin absorption of infrared pump light. The amount of absorbed light, and thus thermoelastic expansion, of the phantom blood vessel wall depends on the oxyhemoglobin/deoxyhemoglobin ratio. Venous blood from the forearm of two volunteers was oxygenated to SO2 levels ranging between 71.7% and 98.3%, typically found in arteriole to arteries. Phantom vessels consist of conduits with a rectangular cross section and central lumen filled with blood. A 765 nm intensity modulated (5Hz) pump laser beam was directed onto the phantom blood vessel. The PhS-OCT system (1328nm) measured displacement amplitude of the outer wall of the 7 phantoms (3 measurements per phantom).

Results: : The oscillation amplitude of the outer wall of the phantom blood vessel decreased linearly with increasing oxygen saturation (slope: 7.5 pm/SO2 unit, R=0.94, RMS^0.5=21 pm). The measurement uncertainty of SO2 was 2.8%.

Conclusions: : We demonstrate in blood phantoms the feasibility of non-invasive depth-resolved measurement of blood oxygenation levels. Future studies will include larger ranges of SO2 (i.e., 40-70% typically found in capillary and veins) as well as in vivo applications. This finding set the stage for depth-resolved imaging of oxygen tension in the retina.

Keywords: diabetic retinopathy • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • blood supply