Assessment of total retinal blood flow using Doppler Fourier Domain Optical Coherence Tomography during systemic hypercapnia and hypocapnia.

The purpose of this study was to investigate changes in total retinal blood flow (RBF) using Doppler Fourier Domain Optical Coherence Tomography (Doppler FD-OCT) in response to the manipulation of systemic partial pressure of CO2 (PETCO2). Double circular Doppler blood flow scans were captured in nine healthy individuals (mean age ± standard deviation: 27.1 ± 4.1, six males) using the RTVue(™) FD-OCT (Optovue). PETCO2 was manipulated using a custom-designed computer-controlled gas blender (RespirAct(™)) connected to a sequential gas delivery rebreathing circuit. Doppler FD-OCT measurements were captured at baseline, during stages of hypercapnia (+5/+10/+15 mmHg PETCO2), return to baseline and during stages of hypocapnia (-5/-10/-15 mmHg PETCO2). Repeated measures analysis of variance (reANOVA) and Tukeys post hoc analysis were used to compare Doppler FD-OCT measurements between the various PETCO2 levels relative to baseline. The effect of PETCO2 on TRBF was also investigated using linear regression models. The average RBF significantly increased by 15% (P < 0.0001) with an increase in PETCO2 and decreased significantly by 10% with a decrease in PETCO2 (P = 0.001). Venous velocity significantly increased by 3.11% from baseline to extreme hypercapnia (P < 0.001) and reduced significantly by 2.01% at extreme hypocapnia (P = 0.012). No significant changes were found in the average venous area measurements under hypercapnia (P = 0.36) or hypocapnia (P = 0.40). Overall, increased and decreased PETCO2 values had a significant effect on RBF outcomes (P < 0.002). In healthy individuals, altered end-tidal CO2 levels significantly changed RBF as measured by Doppler FD-OCT

Optical Coherence Tomography Angiography Vessel Density in Healthy, Glaucoma Suspect, and Glaucoma Eyes.

PurposeThe purpose of this study was to compare retinal nerve fiber layer (RNFL) thickness and optical coherence tomography angiography (OCT-A) retinal vasculature measurements in healthy, glaucoma suspect, and glaucoma patients.MethodsTwo hundred sixty-one eyes of 164 healthy, glaucoma suspect, and open-angle glaucoma (OAG) participants from the Diagnostic Innovations in Glaucoma Study with good quality OCT-A images were included. Retinal vasculature information was summarized as a vessel density map and as vessel density (%), which is the proportion of flowing vessel area over the total area evaluated. Two vessel density measurements extracted from the RNFL were analyzed: (1) circumpapillary vessel density (cpVD) measured in a 750-μm-wide elliptical annulus around the disc and (2) whole image vessel density (wiVD) measured over the entire image. Areas under the receiver operating characteristic curves (AUROC) were used to evaluate diagnostic accuracy.ResultsAge-adjusted mean vessel density was significantly lower in OAG eyes compared with glaucoma suspects and healthy eyes. (cpVD: 55.1 ± 7%, 60.3 ± 5%, and 64.2 ± 3%, respectively; P < 0.001; and wiVD: 46.2 ± 6%, 51.3 ± 5%, and 56.6 ± 3%, respectively; P < 0.001). For differentiating between glaucoma and healthy eyes, the age-adjusted AUROC was highest for wiVD (0.94), followed by RNFL thickness (0.92) and cpVD (0.83). The AUROCs for differentiating between healthy and glaucoma suspect eyes were highest for wiVD (0.70), followed by cpVD (0.65) and RNFL thickness (0.65).ConclusionsOptical coherence tomography angiography vessel density had similar diagnostic accuracy to RNFL thickness measurements for differentiating between healthy and glaucoma eyes. These results suggest that OCT-A measurements reflect damage to tissues relevant to the pathophysiology of OAG

Variable velocity range imaging of the choroid with dual-beam optical coherence angiography

In this study, we present dual-beam Doppler optical coherence angiography with variable beam separation. Altering beam distance, independently of the scanning protocol, provides a flexible way to select the velocity range of detectable blood flow. This system utilized a one-micrometer wavelength light source to visualize deep into the posterior eye, i.e., the choroid. Two-dimensional choroidal vasculature maps of a human subject acquired with different beam separations, and hence with several velocity ranges, are presented. Combining these maps yields a semi-quantitative visualization of axial velocity of the choroidal circulation. The proposed technique may be useful for identifying choroidal abnormalities that occur in pathological conditions of the eye

Comprehensive in vivo micro-vascular imaging of the human eye by dual-beam-scan Doppler optical coherence angiography

Comprehensive angiography provides insight into the diagnosis of vascular-related diseases. However, complex microvascular networks of unstable in vivo organs such as the eye require micron-scale resolution in three dimensions and a high sampling rate to access a wide area as maintaining the high resolution. Here, we introduce dual-beam-scan Doppler optical coherence angiography (OCA) as a label-free comprehensive ophthalmic angiography that satisfies theses requirements. In addition to high resolution and high imaging speed, high sensitivity to motion for detecting tiny blood flow of microvessels is achieved by detecting two time-delayed signals with scanning of two probing beams separated on a sample. We present in vivo three-dimensional imaging of the microvasculature of the posterior part of the human eye. The demonstrated results show that this technique may be used for comprehensive ophthalmic angiography to evaluate the vasculature of the posterior human eye and to diagnose variety of vascular diseases.This paper was published in Optics Express and is made available as an electronic reprint with the permission of OSA. The paper can be found at the following URL on the OSA website: http://www.opticsinfobase.org/abstract.cfm?uri=oe-19-2-1271. Systematic or multiple reproduction or distribution to multiple locations via electronic or other means is prohibited and is subject to penalties under law

Quantitative cerebral blood flow with optical coherence tomography

Absolute measurements of cerebral blood flow (CBF) are an important endpoint in studies of cerebral pathophysiology. Currently no accepted method exists for in vivo longitudinal monitoring of CBF with high resolution in rats and mice. Using three-dimensional Doppler Optical Coherence Tomography and cranial window preparations, we present methods and algorithms for regional CBF measurements in the rat cortex. Towards this end, we develop and validate a quantitative statistical model to describe the effect of static tissue on velocity sensitivity. This model is used to design scanning protocols and algorithms for sensitive 3D flow measurements and angiography of the cortex. We also introduce a method of absolute flow calculation that does not require explicit knowledge of vessel angles. We show that OCT estimates of absolute CBF values in rats agree with prior measures by autoradiography, suggesting that Doppler OCT can perform absolute flow measurements in animal models.National Institutes of Health (U.S.) (Grant number R01-NS057476)National Institutes of Health (U.S.) (Grant number P01NS055104)National Institutes of Health (U.S.) (Grant number P50NS010828)ational Institutes of Health (U.S.) (Grant number K99NS067050)National Institutes of Health (U.S.) (Grant number R01-CA075289-13)United States. Air Force Office of Scientific Research (FA9550-07-1-0014)United States. Dept. of Defense. Medical Free Electron Laser Program (FA9550-07-1-0101

Volumetric and quantitative imaging of retinal blood flow in rats with optical microangiography

In this paper, we present methods for 3D visualization and quantitative measurements of retinal blood flow in rats by the use of optical microangiography imaging technique (OMAG). We use ultrahigh sensitive OMAG to provide high-quality 3D RBF perfusion maps in the rat eye, from which the Doppler angle, as well as the diameters of blood vessels, are evaluated. Estimation of flow velocity (i.e. axial flow velocity) is achieved by the use of Doppler OMAG, which has its origins in phase-resolved Doppler optical coherence tomography. The measurements of the Doppler angle, vessel size, and the axial velocity lead to the quantitative assessment of the absolute flow velocity and the blood flow rate in selected retinal vessels. We demonstrate the feasibility of OMAG to provide 3D microangiograms and quantitative assessment of retinal blood flow in a rat model subjected to raised intra-ocular pressure (IOP). We show that OMAG is capable of monitoring the longitudinal response of absolute blood velocity and flow rate of retinal blood vessels to increased IOP in the rat, demonstrating its usefulness for ophthalmological research

Blood flow rate estimation in optic disc capillaries and vessels using Doppler optical coherence tomography with 3D fast phase unwrapping

The retinal volumetric flow rate contains useful information not only for ophthalmology but also for the diagnosis of common civilization diseases such as diabetes, Alzheimer's disease, or cerebrovascular diseases. Non-invasive optical methods for quantitative flow assessment, such as Doppler optical coherence tomography (OCT), have certain limitations. One is the phase wrapping that makes simultaneous calculations of the flow in all human retinal vessels impossible due to a very large span of flow velocities. We demonstrate that three-dimensional Doppler OCT combined with three-dimensional four Fourier transform fast phase unwrapping (3D 4FT FPU) allows for the calculation of the volumetric blood flow rate in real-time by the implementation of the algorithms in a graphics processing unit (GPU). The additive character of the flow at the furcations is proven using a microfluidic device with controlled flow rates as well as in the retinal veins bifurcations imaged in the optic disc area of five healthy volunteers. We show values of blood flow rates calculated for retinal capillaries and vessels with diameters in the range of 12-150 µm. The potential of quantitative measurement of retinal blood flow volume includes noninvasive detection of carotid artery stenosis or occlusion, measuring vascular reactivity and evaluation of vessel wall stiffness

Real-time eye motion correction in phase-resolved OCT angiography with tracking SLO

In phase-resolved OCT angiography blood flow is detected from phase changes in between A-scans that are obtained from the same location. In ophthalmology, this technique is vulnerable to eye motion. We address this problem by combining inter-B-scan phase-resolved OCT angiography with real-time eye tracking. A tracking scanning laser ophthalmoscope (TSLO) at 840 nm provided eye tracking functionality and was combined with a phase-stabilized optical frequency domain imaging (OFDI) system at 1040 nm. Real-time eye tracking corrected eye drift and prevented discontinuity artifacts from (micro)saccadic eye motion in OCT angiograms. This improved the OCT spot stability on the retina and consequently reduced the phase-noise, thereby enabling the detection of slower blood flows by extending the inter-B-scan time interval. In addition, eye tracking enabled the easy compounding of multiple data sets from the fovea of a healthy volunteer to create high-quality eye motion artifact-free angiograms. High-quality images are presented of two distinct layers of vasculature in the retina and the dense vasculature of the choroid. Additionally we present, for the first time, a phase-resolved OCT angiogram of the mesh-like network of the choriocapillaris containing typical pore openings. © 2012 Optical Society of America

Doppler velocity detection limitations in spectrometer-based versus swept-source optical coherence tomography

Recent advances in Doppler techniques have enabled high sensitivity imaging of biological flow to measure blood velocities and vascular perfusion. Here we compare spectrometer-based and wavelength-swept Doppler OCT implementations theoretically and experimentally, characterizing the lower and upper observable velocity limits in each configuration. We specifically characterize the washout limit for Doppler OCT, the velocity at which signal degradation results in loss of flow information, which is valid for both quantitative and qualitative flow imaging techniques. We also clearly differentiate the washout effect from the separate phenomenon of phase wrapping. We demonstrate that the maximum detectable Doppler velocity is determined by the fringe washout limit and not phase wrapping. Both theory and experimental results from phantom flow data and retinal blood flow data demonstrate the superiority of the swept-source technique for imaging vessels with high flow rates