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Conor Leahy, Harsha Radhakrishnan, Jeffrey L Goldberg, Vivek Srinivasan; Label-free optical quantification of inner retinal oxygen metabolism. Invest. Ophthalmol. Vis. Sci. 2014;55(13):223.
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Non-invasive measurements of inner retinal oxygen metabolism have the potential to enable better detection of retinal diseases where early tissue hypoxia plays a role. Hemoglobin saturation or blood flow measurements, if considered alone, may be misleading, particularly when metabolism and hemodynamics are uncoupled. Retinal metabolic rate of oxygen consumption (RMRO2) is a biomarker that overcomes these limitations, and may yield more accurate tracking of disease progression in diseases such as diabetic retinopathy or glaucoma. Here, by simultaneous imaging of the retina with visible light multispectral oximetry and infrared light Doppler Optical Coherence Tomography (OCT), we demonstrate a methodology for RMRO2 quantification, which does not require exogenous dyes or contrast agents.
To quantify oxygen metabolism, one can apply Fick’s principle and estimate consumption as the difference between the total oxygen inflow rate via arteries and the total oxygen outflow via veins. We demonstrate combined Doppler OCT / multispectral oximetry to quantify inner retinal metabolism in the retina of a Sprague-Dawley rat, anesthetized with 2-2.5% v/v isoflurane. Blood flow is calculated using a robust Doppler OCT method, which does not require explicit knowledge of vessel angle. We simultaneously perform multispectral en-face imaging of the retina using 6 wavelengths with peaks from 560-610 nm, and fit the reflectance measurements with a parametric model of light propagation to determine hemoglobin oxygen saturation.
In a preliminary experiment, Doppler OCT measurements gave a magnitude of total flow of 17.95 μL/min (arterial), and 20.83 μL/min (venous). Retinal oximetry calculations gave the mean oxygen saturations as 52.2±2.9% (arterial) and 35.1±8.1% (venous), which are comparable to previous studies. Applying Fick’s principle yielded a preliminary inner RMRO2 of 392.1 nL/min. Further results will be presented.
We demonstrated an all-optical methodology for quantifying inner retinal oxygen metabolism. Multispectral oximetry and Doppler OCT are compatible techniques that can image the retina simultaneously and provide complementary information on oxygenation and flow. Oxygen metabolism promises to provide a more direct assay of inner retinal tissue status than either flow or hemoglobin saturation measurements alone, and hence has the potential to be a valuable indicator of disease progression.
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