Visible-light Optical Coherence Tomography Research Articles

Visible-Light Optical Coherence Tomography Angiography for Monitoring Laser-Induced Choroidal Neovascularization in Mice.

PurposeThis study sought to determine the earliest time-point at which evidence of choroidal neovascularization (CNV) could be detected with visible-light optical coherence tomography angiography (vis-OCTA) in a mouse model of laser-induced CNV.MethodsVisible light-OCTA was used to study laser-induced CNV at different time-points after laser injury to monitor CNV development and measure CNV lesion size. Measurements obtained from vis-OCTA angiograms were compared with histopathologic measurements from isolectin-stained choroidal flatmounts.ResultsChoroidal neovascularization area measurements between the vis-OCTA system and isolectin-stained choroidal flatmounts were significantly different in area for days 2 to 4 postlaser injury, and were not significantly different in area for days 5, 7, and 14. Choroidal neovascularization area measurements taken from the stained flatmounts were larger than their vis-OCTA counterparts for all time-points. Both modalities showed a similar trend of CNV size increasing from the day of laser injury until a peak of day 7 postlaser injury and subsequently decreasing by day 14.ConclusionsThe earliest vis-OCTA can detect the presence of aberrant vessels in a mouse laser-induced CNV model is 5 days after laser injury. Visible light-OCTA was able to visualize the maximum of the CNV network 7 days postlaser injury, in accordance with choroidal flatmount immunostaining. Visible light-OCTA is a reliable tool in both detecting the presence of CNV development, as well as accurately determining the size of the lesion in a mouse laser-induced CNV model.

Inner retinal oxygen metabolism in the 50/10 oxygen-induced retinopathy model.

Retinopathy of prematurity (ROP) represents a major cause of childhood vision loss worldwide. The 50/10 oxygen-induced retinopathy (OIR) model mimics the findings of ROP, including peripheral vascular attenuation and neovascularization. The oxygen metabolism of the inner retina has not been previously explored in this model. Using visible-light optical coherence tomography (vis-OCT), we measured the oxygen saturation of hemoglobin and blood flow within inner retinal vessels, enabling us to compute the inner retinal oxygen delivery (irDO2) and metabolic rate of oxygen (irMRO2). We compared these measurements between age-matched room-air controls and rats with 50/10 OIR on postnatal day 18. To account for a 61% decrease in the irDO2 in the OIR group, we found an overall statistically significant decrease in retinal vascular density affecting the superficial and deep retinal vascular capillary networks in rats with OIR compared to controls. Furthermore, matching the reduced irDO2, we found a 59% decrease in irMRO2, which we correlated with a statistically significant reduction in retinal thickness in the OIR group, suggesting that the decreased irMRO2 was due to decreased neuronal oxygen utilization. By exploring these biological and metabolic changes in great detail, our study provides an improved understanding of the pathophysiology of OIR model.

Depth-resolved rhodopsin molecular contrast imaging for functional assessment of photoreceptors.

Rhodopsin, the light-sensing molecule in the outer segments of rod photoreceptors, is responsible for converting light into neuronal signals in a process known as phototransduction. Rhodopsin is thus a functional biomarker for rod photoreceptors. Here we report a novel technology based on visible-light optical coherence tomography (VIS-OCT) for in vivo molecular imaging of rhodopsin. The depth resolution of OCT allows the visualization of the location where the change of optical absorption occurs and provides a potentially accurate assessment of rhodopsin content by segmentation of the image at the location. Rhodopsin OCT can be used to quantitatively image rhodopsin distribution and thus assess the distribution of functional rod photoreceptors in the retina. Rhodopsin OCT can bring significant impact into ophthalmic clinics by providing a tool for the diagnosis and severity assessment of a variety of retinal conditions.

Visible light optical coherence tomography measures retinal oxygen metabolic response to systemic oxygenation.

The lack of capability to quantify oxygen metabolism noninvasively impedes both fundamental investigation and clinical diagnosis of a wide spectrum of diseases including all the major blinding diseases such as age-related macular degeneration, diabetic retinopathy, and glaucoma. Using visible light optical coherence tomography (vis-OCT), we demonstrated accurate and robust measurement of retinal oxygen metabolic rate (rMRO2) noninvasively in rat eyes. We continuously monitored the regulatory response of oxygen consumption to a progressive hypoxic challenge. We found that both oxygen delivery, and rMRO2 increased from the highly regulated retinal circulation (RC) under hypoxia, by 0.28 ± 0.08 μL min−1 (p < 0.001), and 0.20 ± 0.04 μL min−1 (p < 0.001) per 100 mmHg systemic pO2 reduction, respectively. The increased oxygen extraction compensated for the deficient oxygen supply from the poorly regulated choroidal circulation. Results from an oxygen diffusion model based on previous oxygen electrode measurements corroborated our in vivo observations. We believe that vis-OCT has the potential to reveal the fundamental role of oxygen metabolism in various retinal diseases.

Human retinal imaging using visible-light optical coherence tomography guided by scanning laser ophthalmoscopy.

We achieved human retinal imaging using visible-light optical coherence tomography (vis-OCT) guided by an integrated scanning laser ophthalmoscopy (SLO). We adapted a spectral domain OCT configuration and used a supercontinuum laser as the illumating source. The center wavelength was 564 nm and the bandwidth was 115 nm, which provided a 0.97 µm axial resolution measured in air. We characterized the sensitivity to be 86 dB with 226 µW incidence power on the pupil. We also integrated an SLO that shared the same optical path of the vis-OCT sample arm for alignment purposes. We demonstrated the retinal imaging from both systems centered at the fovea and optic nerve head with 20° × 20° and 10° × 10° field of view. We observed similar anatomical structures in vis-OCT and NIR-OCT. The contrast appeared different from vis-OCT to NIR-OCT, including slightly weaker signal from intra-retinal layers, and increased visibility and contrast of anatomical layers in the outer retina.

Measuring oxygen saturation in retinal and choroidal circulations in rats using visible light optical coherence tomography angiography.

Visible light optical coherence tomography (vis-OCT) has demonstrated its capability of measuring vascular oxygen saturation (sO2) in vivo. Enhanced by OCT angiography, the signal from microvasculature can be further isolated and directly used for sO2 extraction. In this work, we extended the theoretical formulation for OCT angiography-based oximetry by incorporating the contribution from motion contrast enhancement. We presented a new method to eliminate the associated confounding variables due to blood flow. First, we performed in vitro experiments to verify our theory, showing a stable spectral derivative within the selected wavelength bands for sO2 extraction. Then, we tested our method in vivo to measure retinal sO2 in rats inhaling different gas mixtures: normal air, 5% CO2, pure O2, and 10% O2. Absolute sO2 values in major arterioles and venules in the retinal circulation can be accurately measured. In addition, we demonstrated the relative changes of sO2 can be measured non-invasively from choriocapillaris immediately underneath the retinal pigmented epithelium (RPE) in rodents.

In vivo functional microangiography by visible-light optical coherence tomography.

Although hemoglobin oxygen saturation (sO2) in the microvasculature is an essential physiological parameter of local tissue functions, non-invasive measurement of microvascular sO2 is still challenging. Here, we demonstrated that visible-light optical coherence tomography (vis-OCT) can simultaneously provide three-dimensional anatomical tissue morphology, visualize microvasculature at the capillary level, and measure sO2 from the microvasculature in vivo. We utilized speckle contrast caused by the moving blood cells to enhance microvascular imaging. We applied a series of short-time inverse Fourier transforms to obtain the spectroscopic profile of blood optical attenuation, from which we quantified sO2. We validated the sO2 measurement in mouse ears in vivo through hypoxia and hyperoxia challenges. We further demonstrated that vis-OCT can continuously monitor dynamic changes of microvascular sO2.

Visible-light optical coherence tomography for retinal oximetry

We applied a visible-light spectroscopic optical coherence tomography (vis-OCT) for in vivo retinal oximetry. To extract hemoglobin oxygen saturation (sO(2)) in individual retinal vessels, we established a comprehensive analytical model to describe optical absorption, optical scattering, and blood cell packing factor in the whole blood and fit the acquired vis-OCT signals from the bottom of each imaged vessel. We found that averaged sO(2) values in arterial and venous bloods were 95% and 72%, respectively.