Assessing total retinal blood flow using ultrahigh speed, swept source OCT at 1050 nm
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In the past two decades, the applications of optical monitoring for non-invasive assessment of glucose have been pursued with limited success. We have investigated potential application of optical coherence tomography (OCT) for non- invasive and continuous monitoring of blood glucose concentration. An OCT system with the wavelength of 1300 nm was used in phantom and in vivo studies. Polystyrene spheres with the diameter of 0.76 micrometers were used as scatterers in aqueous solutions in the phantom studies. We have found 4.5% change of the OCT signal slope as a function of glucose concentration in the range from 0 to 100 mM in the phantoms. This is in good agreement with theoretical calculations performed using Mie's theory. Bolus glucose injection and glucose clamping experiments were performed in New Zealand rabbits and Yucatan micropigs. OCT images were obtained from skin (dorsal area of the pigs and rabbit ear). Our pilot studies show close correlation between actual blood glucose concentration and slope of the OCT signals. The slope decreased substantially (about 40% in tissues in vivo) with the increase of blood glucose concentration from 4 to 30 mM. In conclusion, we have demonstrated that glucose-induced changes in optical properties of skin can be monitored by OCT suggesting that a new OCT-based optical sensor could be developed for sensitive and accurate non-invasive monitoring of glucose concentration in vivo.
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A line-field, spectral domain optical coherence tomography (LF-SD-OCT) system was developed for in-vivo, noncontact, cellular resolution imaging of biological tissue. The LF-SD-OCT system utilizes a broadband laser with a spectrum centered at ~790 nm and spectral bandwidth of ~140 nm to achieve 1.8 μm axial and ~5 μm isotropic lateral resolution in biological tissue. A high speed 2D camera was used to achieve frame rate of 2.5k B-scans/s. The system's SNR was measured to be 92 dB at 100 μm away from the zero-delay line for 2.8 mW optical power incident on the imaged object, with 18 dB roll-off over a scanning range of 1 mm. The LF-SD-OCT system was used to image the cellular structure of cucumber and the cucumber seed where the high spatial resolution was sufficient to resolve cellular nuclei. Then the system was used to image in-vivo human skin (fingertip), where the spiral structures of the sweat glands, as well as a large number of capillaries were observed in the epidermal layer. Images of the healthy human cornea were also acquired from locations near the corneal apex and the periphery and showed the tissue cellular structure and vasculature. Currently, the corneal images were acquired ex-vivo, as we are waiting for ethics clearance to conduct in-vivo corneal imaging studies with the novel LF-SD-OCT system.
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Biological Imaging
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Doppler OCT provides depth-resolved information on flow in biological tissues. In this article, we demonstrate ultrahigh speed swept source/Fourier domain OCT for visualization and quantitative assessment of retinal blood flow. Using swept laser technology, the system operated in the 1050-nm wavelength range at a high axial scan rate of 200 kHz. The rapid imaging speed not only enables volumetric imaging with high axial scan densities, but also enables measurement of high flow velocities in the central retinal vessels. Deep penetration in the optic nerve and lamina cribrosa was achieved by imaging at 1-µm wavelengths. By analyzing en-face images extracted from 3D Doppler data sets, absolute flow in single vessels as well as total retinal blood flow was measured using a simple and robust protocol that does not require measurement of Doppler angles. The results from measurements in healthy eyes suggest that ultrahigh speed swept source/Fourier domain OCT could be a promising technique for volumetric imaging of retinal vasculature and quantitation of retinal blood flow in a wide range of retinal diseases.
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Purpose. To demonstrate the ability of a new high-speed polarization-sensitive optical coherence tomography (PS-OCT) system for retinal imaging at 1040 nm. Methods. A new polarization-sensitive swept source OCT system in the 1 μm wavelength range is used to image the retina of healthy volunteers. The instrument is operated at an A-scan rate of 100 kHz which is about three times faster than previously reported PS-OCT instruments in this wavelength region. The increased imaging speed can be used to record densely sampled volumes of the retina. Moreover, it enables averaging of several B-scans recorded at the same location to obtain high-definition B-scans without the use of an eye tracker. Results. Polarization-sensitive images of healthy volunteers clearly show the retinal pigment epithelium as a depolarizing layer. In addition, the good tissue penetration of the system allows the visualization of the sclera, which is highly birefringent and therefore shows increased image contrast with PS-OCT. Conclusions. PS-OCT in the 1 μm wavelength region shows similar polarization effects as in the 840 nm wavelength range. The high speed enables averaging of several B-scans to obtain high-definition polarization-sensitive images. The new system provides excellent penetration depth into the choroid and sclera.
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A swept-source dual-wavelength photothermal (DWP) optical coherence tomography (OCT) system is demonstrated for quantitative imaging of microvasculature oxygen saturation. DWP-OCT is capable of recording three-dimensional images of tissue and depth-resolved phase variation in response to photothermal excitation. A 1,064-nm OCT probe and 770-nm and 800-nm photothermal excitation beams are combined in a single-mode optical fiber to measure microvasculature hemoglobin oxygen saturation (SO 2 ) levels in phantom blood vessels with a range of blood flow speeds (0 to 17 mm/s ). A 50-μm-diameter blood vessel phantom is imaged, and SO 2 levels are measured using DWP-OCT and compared with values provided by a commercial oximeter at various blood oxygen concentrations. The influences of blood flow speed and mechanisms of SNR phase degradation on the accuracy of SO 2 measurement are identified and investigated.
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The design of a multi-functional fiber-based Optical Coherence Tomography (OCT) system for human retinal imaging with < 2 micron axial resolution in tissue is described. A detailed noise characterization of two supercontinuum light sources with different pulse repetition rates is presented. The higher repetition rate and lower noise source is found to enable a sensitivity of 96 dB with 0.15 mW light power at the cornea and a 98 microsecond exposure time. Using a broadband (560 ± 50 nm), 90/10, fused single-mode fiber coupler designed for visible wavelengths, the sample arm is integrated into an ophthalmoscope platform, similar to current clinical OCT systems. To demonstrate the instrument’s range of operation, in vivo structural retinal imaging is also shown at 0.15 mW exposure with 10,000 and 70,000 axial scans per second (the latter comparable to commercial OCT systems), and at 0.03 mW exposure and 10,000 axial scans per second (below maximum permissible continuous exposure levels). Lastly, in vivo spectroscopic imaging of anatomy, saturation, and hemoglobin content in the human retina is also demonstrated.
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Noninvasive in vivo functional optical imaging of the intact retina is demonstrated by using high-speed, ultrahigh-resolution optical coherence tomography (OCT). Imaging was performed with 2.8 μm resolution at a rate of 24,000 axial scans per second. A white-light stimulus was applied to the dark-adapted rat retina, and the average reflectivities from different intraretinal layers were monitored as a function of time. A 10%-15% increase in the average amplitude reflectance of the photoreceptor outer segments was observed in response to the stimulus. The spatial distribution of the change in the OCT signal is consistent with an increase in backscatter from the photoreceptor outer segments. To our knowledge, this is the first in vivo demonstration of OCT functional imaging in the intact retina.
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A high speed (47,000 A-scan/s), high resoluiton FD-OCT system, operating in the 1060nm wavelength range was used to acquire in-vivo 3D image of healthy and pathological rat retinas. The images were acquired with ~4.3µm axial and ~5µm lateral resolution in the rat eye and 102dB sensitivity at 1.3mW optical power of the imaging beam. The images of the healthy rat retinas show increased penetration into the choroid, clear visualization of all intra-retinal layers and the choroidal blood network, as well as part of the underlying sclera. The high imaging resolution of the OCT system is also sufficient for resolving tiny capillaries imbedded in the inner - and outer plexiform layers of the retina. The high data acquisition rate of the FD-OCT system combined with the high axial resolution is also suitable for probing light induced physiological processes in the retina simultaneously with the morphological imaging.
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