Spectral-domain Doppler Optical Coherence Research Articles

Dual-beam delay-encoded all fiber Doppler optical coherence tomography for in vivo measurement of retinal blood flow

In this paper, we propose and demonstrate a dual-beam delay-encoded Doppler spectral domain optical coherence tomography (OCT) system for in vivo measurement of absolute retinal blood velocity and flow with arbitrary orientation. The incident beam is split by a beam displacer into two probe beams of the single-spectrometer spectral domain OCT system with orthogonal polarization states and an optical path length delay. We validate our approach with a phantom and in vivo experiments of human retinal blood flow, respectively.

Phase unwrapping for Doppler spectral domain optical coherence tomography flow measurement.

Doppler optical coherence tomography (OCT) offers additional flow velocity information, which extends the application of OCT. Phase wrapping is the inherent problem that limits measureable range of Doppler OCT. We propose a phase unwrapping method which is suitable for correcting phase in Doppler OCT images. Points (pixels) in flow region are divided into groups according to the radial distance. Points in the same group are supposed to have close velocity. Phase unwrapping algorithm begins at the boundary layer group and is performed sequentially toward the center. Using the proposed criterion, points in a group are separated into two categories, signal points and noise points. Wrapping rounds are determined for signal points phase unwrapping. Mean value of the corrected signal points replaces the noise points for noise reduction. The method is validated with capillary tube flow phantom and in vivo blood flow.

Retinal perfusion changes in radiation retinopathy.

To investigate retinal blood flow and oxygen saturation changes in patients diagnosed with retinopathy following plaque radiation treatment to treat choroidal melanoma. Eight patients (mean age 55.75years, SD 12.58years) who have developed unilateral ischaemic radiation-related retinopathy as confirmed by wide-field fluorescein angiography were recruited for the study. The fellow eye with no other ocular or retinal pathology was used as control. Both eyes underwent measurement of total retinal blood flow (TRBF) and retinal blood oxygen saturation using prototype methodologies of Doppler Spectral Domain Optical Coherence Tomography (OCT) and Hyperspectral Retinal Camera, respectively. The average TRBF in the retinopathy eye was significantly lower compared to the fellow eye (33.48±12.73μl/min versus 50.37±15.26μl/min; p=0.013). The arteriolar oxygen saturation (SaO2 ) and venular oxygen saturation (SvO2 ) were higher in the retinopathy eye compared to the fellow eye (101.11±4.26%, versus 94.45±5.79%; p=0.008) and (62.96±11.05% versus 51.24±6.88%, p=0.051), respectively. The ionizing radiation seems to have an impact on the TRBF, SaO2 and SvO2 , clinically presenting similar to a rapidly developing diabetic retinopathy. The results show an altered retinal vascular physiology in patients with radiation-related retinopathy.

Retinal Oximetry and blood flow

SummaryThe retina has highest metabolic demand compared to any other tissue in the human body and regulation of the retinal blood flow, blood oxygen saturation (SO2) and thereby oxygen delivery (DO2) are crucial to preserve vision and function. The study reports inner retinal DO2 and consumption (VO2) during controlled and stable normoxia, hyperoxia and hypoxia in humans. Eleven subjects underwent measurement of total retinal blood flow (TRBF) and retinal blood oxygen saturation (SO2) using prototype methodologies of Doppler Spectral Domain Optical Coherence Tomography and Metabolic Hyperspectral Camera, respectively. TRBF decreased significantly (p = 0.010) from 43.17 μl/min (+12.7) to 36.23 μl/min (+4.6) during hyperoxia, conversely, TRBF increased significantly (p < 0.008) to 52.89 μl/min (+10.9) from baseline during hypoxia. The average inner retinal O2 delivery during normoxia was 8.48 mlO2/100 g/min and inner retinal consumption was 3.64 mlO2/100 g/min and these values changed during provocation to maintain a stable DO2 and VO2. Change in TRBF and SO2 reflect metabolic autoregulatory function of the retinal tissue indicating that retinal blood flow and SO2 are able to precisely compensate for changes in inspired oxygen.

Intervisit Repeatability of Retinal Blood Oximetry and Total Retinal Blood Flow Under Varying Systemic Blood Gas Oxygen Saturations

The aim of the study is to validate and calibrate the Doppler spectral-domain optical coherence tomography (SD-OCT) derived total retinal blood flow (TRBF) and metabolic hyperspectral retinal camera (MHRC) derived oxygen saturation (SO2) of major retinal vessels in human volunteers using a novel and exact provocation technique (RespirAct) that allows the precise control of the end-tidal partial pressure of oxygen (PETO2). Between visit repeatability of the TRBF and retinal blood SO2 also were studied. One eye of 11 young healthy subjects was chosen randomly for the study. Total retinal blood flow and retinal SO2 measurements were obtained under conditions of normoxia, hyperoxia, and hypoxia. The order of hyperoxia and hypoxia was randomized between subjects. The measurements were repeated after a week interval. When the arterial PETO2 was increased from baseline (PETO2 = 100 mm Hg) to 200 and 300 mm Hg, the TRBF significantly reduced (P = 0.02) from 44.60 (±8.9) to 40.28 (±8.9) and 36.23 (±4.6) μL/min. Lowering the arterial PETO2, from baseline to 80, 60, and 50 mm Hg, TRBF significantly increased (P = 0.04) from 43.17 (±12.7) to 45.19 (±5.5), 49.71 (±13.4), and 52.89 (±10.9) μL/min with simultaneous reduction in the arterial blood SO2 content from 99.3% (±5.8) to 95.6% (±5.1), 89.6% (±2.8), and 83.3% (±3.9), respectively (P = 0.00). The coefficient of repeatability (COR) of TRBF, retinal arterial, and venous blood SO2 values are 21.8 μL/min, 18.4%, and 15.2%, respectively. Total retinal blood flow and retinal blood SO2 measurements performed under safe levels of hypoxia and hyperoxia were repeatable in healthy adults over the range of SO2 investigated.

Absolute velocity measurement using three-beam spectral-domain Doppler optical coherence tomography

We report the development of a three-beam spectral-domain Doppler optical coherence tomography setup that allows single interferometer-based measurement of absolute flow velocity. The setup makes use of galvo-based phase shifting to remove complex conjugate mirror artifact and a beam displacer in the sample arm to avoid cross talk image. The results show that the developed approach allows efficient utilization of the imaging range of the spectral-domain optical coherence tomography setup for three-beam-based velocity measurement.

Vascular distribution imaging of dorsal skin window chamber in mouse with spectral domain optical coherence tomography

Doppler optical coherence tomography or optical Doppler tomography (ODT) has been demonstrated to spatially localize flow velocity mapping as well as to obtain images of microstructure of samples simultaneously. In recent decades, spectral domain Doppler optical coherence tomography (OCT) has been applied to observe three-dimensional (3D) vascular distribution. In this study, we developed a spectral domain optical coherence tomography system (SD-OCT) using super luminescent diode (SLD) as light source. The center wavelength of SLD is 835 nm with a 45-nm bandwidth. Theoretically, the transverse resolution, axial resolution and penetration depth of this SD-OCT system are 6.13 μm, 6.84 μm and 3.62 mm, respectively. By imaging mouse model with dorsal skin window chamber, we obtained a series of real-time OCT images and reconstructed 3D images of the specific area inside the dorsal skin window chamber by Amira. As a result, we can obtain the clear and complex distribution images of blood vessels of mouse model.

Grader learning effect and reproducibility of Doppler Spectral‐Domain Optical Coherence Tomography derived retinal blood flow measurements

To investigate grader learning effect and to quantify intergrader reproducibility of Doppler Spectral-Domain Optical Coherence Tomography (SD-OCT) derived retinal blood flow measurements. Fifteen healthy young subjects (mean age 28.44; SD 3 years) underwent Doppler SD-OCT scans of one eye using the circumpapillary double circular scan protocol of the Optovue RTVue by one of two experienced operators. One trained (i.e. having undergone certification) and one novice (i.e. preliminary training comprising five standard practice data sets) individual then graded a standardized set of scans, consisting of 15 data sets (session 1) using custom Doppler Optical Coherence Tomography of Retinal Circulation (DOCTORC) software. One week later (session 2), the novice grader underwent further training by grading an additional 15 practice data sets and then both graders subsequently regraded the original 15 data sets. Measurements achieved by a novice grader during session 1 showed a trend to be higher in terms of total retinal venous blood flow (TRBF) and also to be significantly (p = 0.03) higher for venous area, compared with a trained grader. Session 2 results were not significantly different for either grader. The mean TRBF for session 2 for the trained and novice grader was 45.29 ± 9.28 μl/min and 44.39 ± 7.36 μl/min, respectively. The coefficient of repeatability (COR) of session 2 TRBF values between the trained and novice grader was 8.09 μl/min. There is a grader learning effect which impacts the venous area measurements. Reproducible and repeatable retinal blood flow measurements were achieved among trained graders using DOCTORC software.

Retinal blood flow and vascular reactivity in chronic smokers.

The aim of this study was to investigate the impact of cigarette smoking in otherwise healthy young individuals on retinal blood flow (RBF) and vascular reactivity (RVR). An automated gas flow controller (RespirAct) was used to achieve normoxic hypercapnia in 10 nonsmokers (mean age 28.9; SD 4.6 years) and nine smokers (mean age 27.55; SD 4.7 years). Retinal blood flow measurements were obtained using a prototype Doppler spectral-domain optical coherence tomographer (SD-OCT) and bidirectional laser Doppler velocimetry and simultaneous vessel densitometry during baseline, normoxic hypercapnia, and recovery. Group mean PETCO2 (end-tidal partial pressure of CO2) was increased by 15.9% in the nonsmoking group and by 15.7% in the smoking group, with a concomitant increase in PETO2 (end-tidal partial pressure of O2) by approximately 1.5% to 2% in both groups. In nonsmokers, retinal arteriolar diameter (P < 0.0001), centerline velocity (P = 0.0004), and blood flow (P < 0.0001) significantly increased during normoxic hypercapnia. Similarly, the venous area (P = 0.0418), venous velocity (P = 0.0068), and total venous RBF (P < 0.0001), as measured by the prototype Doppler SD-OCT, significantly increased. In smokers, normoxic hypercapnia resulted in a significant increase in velocity (P = 0.0019), flow (P = 0.0029), and total venous RBF (P = 0.002). Comparing smokers and nonsmokers, the percentage change in arteriolar diameter (P = 0.0379) and blood flow (P = 0.0101) was significantly lower in the smoking group. There was no significant difference in baseline PETCO2 level between smokers and nonsmokers. Retinal vascular reactivity in response to normoxic hypercapnia is significantly reduced in young, healthy smokers compared with nonsmokers.

Measurement of blood flow velocity profiles in retinal arterioles and venules using spectral-domain doppler optical coherence tomography in healthy subjects

Measurement of blood flow velocity profiles in retinal arterioles and venules using spectral-domain doppler optical coherence tomography in healthy subjects

In vitroandin vivothree-dimensional velocity vector measurement by three-beam spectral-domain Doppler optical coherence tomography

We developed a three-beam Doppler optical coherence tomography (OCT) system that enables measurement of the velocity vector of moving particles in three-dimensions (3-D). The spatial orientation as well as the magnitude of motion can be determined without prior knowledge of the geometry of motion. The system combines three spectral-domain OCT interferometers whose sample beams are focused at the sample by a common focusing lens at three different angles. This provides three spatially independent velocity components simultaneously from which the velocity vector can be reconstructed. We demonstrate the system in a simple test object (rotating disc), a flow phantom, and for blood flow measurements in the retina of a healthy human subject. Measurements of blood flow at a venous bifurcation achieve a good agreement between in- and outflow and demonstrate the reliability of the method.

Automatic retinal vessel segmentation based on active contours method in Doppler spectral-domain optical coherence tomography

We achieved fast and automatic retinal vessel segmentation by employing the active contours method in Doppler spectral-domain optical coherence tomography (SD-OCT). In a typical OCT B-scan image, we first extracted the phase variations between adjacent A-lines and removed bulk motion. Then we set the initial contour as the boundary of the whole image and iterated until all of the segmented vessel contours became stabilized. Using a typical office computer, the whole segmentation took no more than 50 s, making real-time retinal vessel segmentation possible. We tested the active contours method segmentation in both controlled phantom and in vivo rodent eye images.

Visualization and measurement of capillary-driven blood flow using spectral domain optical coherence tomography

Capillary-driven flow (CD-flow) in microchannels plays an important role in many microfluidic devices. These devices, the most popular being those based in lateral flow, are becoming increasingly used in health care and diagnostic applications. CD-flow can passively pump biological fluids as blood, serum or plasma, in microchannels and it can enhance the wall mass transfer by exploiting the convective effects of the flow behind the meniscus. The flow behind the meniscus has not been experimentally identified up to now because of the lack of high-resolution, non-invasive, cross-sectional imaging means. In this study, spectral-domain Doppler optical coherence tomography is used to visualize and measure the flow behind the meniscus in CD-flows of water and blood. Microchannels of polydimethylsiloxane and glass with different cross-sections are considered. The predictions of the flow behind the meniscus of numerical simulations using the power-law model for non-Newtonian fluids are in reasonable agreement with the measurements using blood as working fluid. The extension of the Lucas-Washburn equation to non-Newtonian power-law fluids predicts well the velocity of the meniscus of the experiments using blood.

Three-Dimensional Visualization of Ocular Vascular Pathology by Optical Coherence Angiography In Vivo

To demonstrate the clinical application of a noninvasive, three-dimensional, vascular imaging technique called Doppler optical coherence angiography (OCA). To evaluate the vascular architecture of polypoidal choroidal vasculopathy (PCV) using Doppler OCA. The authors prospectively examined the eyes of four healthy subjects and 15 PCV patients. Three-dimensional vascular flow imaging was performed using high-speed, high-resolution, and high-penetration spectral-domain Doppler optical coherence tomography. Two-dimensional images of the retina, choroid, and vascular lesions were obtained simultaneously. Distribution of blood flow detected by Doppler OCA imaging corresponded well with that by indocyanine angiographic imaging. PCV lesions were localized in the space between the retinal pigment epithelium and the Bruch's membrane. The authors found using Doppler OCA that PCV lesions are similar in architecture to choroidal neovascularization in age-related macular degeneration. Doppler OCA facilitates rapid and noninvasive examination of exudative macular diseases.

Monitoring of drug and stimulation induced cerebral blood flow velocity changes in rat sensory cortex using spectral domain Doppler optical coherence tomography

Doppler optical coherence tomography (DOCT) provides a novel method to measure blood flow velocity in vessels with diameter at micrometer scale. In this study, a developed spectral domain DOCT system is applied to monitor cerebral blood flow velocity changes in a rat. An animal model with a cranial window is used, and by application of a drug, light, and electric stimulations, changes in blood flow velocity of the pial artery in sensory cortex are measured in real time. The results show significant differences in blood flow velocity before and after drug administration or light and electric stimulations, demonstrating the feasibility of DOCT in cerebral microcirculation study. Given its noninvasive nature, high spatial resolution, high velocity sensitivity, and high imaging speed, DOCT shows great promise in brain research by imaging blood flow changes at micrometer scale vessels, which helps to understand the pathogenesis of cerebral diseases and neurodegenerative diseases.

Velocity Variation Assessment of Red Blood Cell Aggregation with Spectral Domain Doppler Optical Coherence Tomography

We propose spectral domain Doppler optical coherence tomography (SD-D-OCT) to qualitatively measure red blood cell aggregation. Variance/standard deviation (SD) of the Doppler frequency spectrum in Doppler variance imaging of flowing blood under shearing conditions was developed as a new aggregation index. In in vitro microchannel-flow experiments, porcine blood at various hematocrits with aggregation characteristics induced by dextran 500 or at the presence of plasma fibrinogen was measured by a SD-D-OCT system with a spectrum centered at 1310 nm. The effects of shear rate, hematocrit, aggregation level on the SD values were investigated. The results demonstrate that Doppler variance imaging using the SD value was capable of differentiating the normal and the aggregated blood with hematocrits of 30–55% flowing at a shear rate of 40–60 s−1. The SD value was found to be nonsignificant hematocrit-dependent. It is also a sensitive and repeatable aggregation index for comparison between nonaggregated and aggregated blood samples.

Parabolic BM-scan technique for full range Doppler spectral domain optical coherence tomography

A full range spectral domain optical coherence tomography (SD-OCT) technique that relies on the linear phase modulation of one of the interferometer arms has been widely utilized. Although this method is useful, the mirror image elimination is not perfect for samples in which regions with high axial motion exist. In this paper, we introduce a new modulation pattern to overcome this mirror image elimination failure. This new modulation is a parabolic phase modulation in the transverse scanning direction, and is applied to the SD-OCT reference beam by an electro-optic modulator. Flow phantom and in vivo experiments demonstrate that for moving structures with large velocities, this parabolic phase modulation technique presents better mirror image elimination than a standard linear phase modulation method. A direct consequence of this enhanced mirror image removal is an improved velocity range obtained with phase-resolved Doppler imaging. Consequently, applying the proposed technique in retinal blood flow measurements may be useful for ophthalmologic diagnosis.

Transit-time analysis based on delay-encoded beam shape for velocity vector quantification by spectral-domain Doppler optical coherence tomography

We propose a transit-time based method to ascertain the azimuth angle of a velocity vector by spectral-domain Doppler optical coherence tomography (DOCT), so that three-dimensional (3-D) velocity vector can be quantified. A custom-designed slit plate with predetermined slit orientation is placed into the sample beam to create three delay-encoded sub-beams of different beam shape for sample probing. Based on the transit-time analysis for Doppler bandwidth, the azimuth angle within 90 degrees range is evaluated by exploitation of the complex signals corresponding to three path length delays. 3-D velocity vector is quantified through further estimating of Doppler angle and flow velocity by combined Doppler shift and Doppler bandwidth measurements. The feasibility of the method is demonstrated by good agreement between the determined azimuth angles and the preset ones, and further confirmed by velocity vector measurement of flowing solution inside a capillary tube.

Quantification of cocaine-induced cortical blood flow changes using laser speckle contrast imaging and Doppler optical coherence tomography

We present a dual-imaging technique combining laser speckle contrast imaging and spectral-domain Doppler optical coherence tomography to enable quantitative characterization of local cerebral blood flow (CBF) changes in rat cortex in response to drug stimulus (e.g., cocaine) at high spatiotemporal resolutions. To examine the utility of this new technique, animal experiments were performed to study the influences of anesthetic regimes (e.g., isoflurane, alpha-chloralose) on the pharmadynamic effects of acute cocaine challenge. The results showed that cocaine-evoked CBF patterns (e.g., increases in alpha-chloralose and decreases in isoflurane regimes) were quantitatively characterized, thus rendering it a potentially useful tool for imaging studies of brain functions.

Optical coherence Doppler tomography quantifies laser speckle contrast imaging for blood flow imaging in the rat cerebral cortex

A dual-imaging modality is demonstrated for high-resolution quantitative imaging of local cerebral blood flow in the rat cortex by combining simultaneous spectral-domain Doppler optical coherence tomography (SDOCT) and full-field laser speckle contrast imaging (LSCI). Preliminary studies in tissue flow phantom and cocaine-induced cerebral blood flow changes indicated that by correlating coregistered cortical arterial blood flow, the relative measurement of flow changes by LSCI could be accurately calibrated by the absolute flow imaging provided by SDOCT (least square fit, r(2) approximately 0.96). Quantitative LSCI of cerebral blood flow is crucial to the quantitative analyses of the spatiotemporal hemodynamics of functional brain activations and thus improved understanding of neural process.