Doppler Optical Coherence Tomography Research Articles

Relationship Between Macular Vessel Density and Total Retinal Blood Flow in Primary Open-angle Glaucoma.

An association between macular vessel density (VD) and total retinal blood flow (TRBF) was demonstrated in subjects with primary open-angle glaucoma (POAG) and visual field (VF) loss. The purpose of this study was to report relationships of macular VD metrics and TRBF in POAG. A total of 24 POAG and 19 healthy control subjects participated in the study. Subjects underwent optical coherence tomography and angiography for measurements of inner retinal thickness (IRT), VD, and spacing between large vessels (SLV) and small vessels (SSV). Doppler optical coherence tomography imaging was performed for TRBF measurement. In POAG subjects, automated perimetry was performed and VF loss expressed as mean deviation was measured. Compared with the control group, POAG group had decreased VD, TRBF, IRT, and increased SLV (P<0.0001). Decreased VD (Pearson correlation, r=0.51; P<0.0001; N=43) and increased SLV (Spearman correlation, rs=-0.47; P=0.001) were correlated with decreased TRBF. Decreased VD and SSV (r≥0.39; P≤0.001; N=43) and increased SLV (rs=-0.71; P<0.0001) were associated with decreased IRT. Decreased VF mean deviation was correlated with decreased VD, SSV, IRT (r≥0.53; P≤0.001; N=24), and with increased SLV (rs=-0.84; P<0.0001). The finding of an association between macular VD and TRBF supports the role of vascular factors in the pathophysiology of POAG and potential conduct of future studies aimed at identifying multiple image-based vascular metrics for disease diagnosis.

Prenatal alcohol exposure causes structural and functional cardiac defects, which can be prevented with folate supplementation

Increased regurgitant blood flow has been linked to endocardial cushion defects and resultant congenital heart diseases (CHDs). Prenatal alcohol exposure (PAE) has been shown to alter early blood flow resulting in abnormal endocardial cushions and CHDs. Compounds, including folic acid (FA), mitigate PAE effects and prevent CHDs, but few studies have assessed their effects on blood flow. We modeled binge drinking in avian embryos at gastrulation. Embryos were exposed to ethanol alone, FA (3.2 μg/egg) alone, and the two simultaneously. We quantified in cardiac looping stages (equivalent to 4 weeks of human gestation) regurgitant blood flow with Doppler optical coherence tomography (OCT) and endocardial cushion volumes using OCT imaging. Incidences of abnormal body curvature and heart rates were also measured. Embryos exposed to ethanol showed significantly increased regurgitant blood flow compared to controls, while embryos given FA with ethanol had significantly reduced regurgitant blood flow but did not return to control levels. Ethanol exposure led to significantly smaller, abnormal endocardial cushions and the addition of FA improved their size, but they remained smaller than controls. Abnormal body curvatures after PAE were reduced in incidence but not fully prevented by FA. FA supplementation partially alleviated PAE induced abnormal cardiovascular function and morphology. Normal blood flow and endocardial cushions are both required to produce a healthy four-chambered heart. These findings support that FA supplementation should begin early in pregnancy to prevent heart as well as neural tube defects. Investigations into the efficacy of combinations of compounds to prevent PAE-induced defects is warranted.

Minimally-invasive diagnostic approaches in periodontics: laser Doppler imaging and optical coherence tomography

Minimally-invasive diagnostic approaches in periodontics: laser Doppler imaging and optical coherence tomography

Evaluation on tissue vibration mechanism by visco-elastic diagnosis using Ultrasound Assisted Doppler OCT (UA-OCDV)

Evaluation on tissue vibration mechanism by visco-elastic diagnosis using Ultrasound Assisted Doppler OCT (UA-OCDV)

Plexus-specific effect of flicker-light stimulation on the retinal microvasculature assessed with optical coherence tomography angiography.

In neural tissues, the coupling between neural activity and blood flow is a physiological key principle in blood flow regulation. We used optical coherence tomography angiography to investigate stimulus-evoked hemodynamic responses in different microvascular layers of the human retina. Twenty-two healthy subjects were included. Vessel density before and during light stimulation was measured using optical coherence tomography angiography and assessed for the superficial, intermediate, and deep capillary plexus of the retinal circulation. Volumetric blood flow was measured using a custom-built Doppler optical coherence tomography system. Our results show that flicker stimulation induced a significant increase in the vessel density of +9.9 ± 6.7% in the superficial capillary plexus, +6.6 ± 1.7% in the intermediate capillary plexus, and +4.9 ± 2.3% in the deep capillary plexus. The hyperemic response of the superficial capillary plexus was significantly higher compared to the intermediate capillary plexus (P = 0.02) and deep capillary plexus (P = 0.002). Volumetric retinal blood flow increased by +39.9 ± 34.9% in arteries and by +29.8 ± 16.8% in veins. In conclusion, we showed a strong increase in the retinal microvascular density in response to light stimulation, with the most pronounced effect in the superficial capillary plexus. This is compatible with the hypothesis that the microvasculature exerts an important function in mediating functional hyperemia in humans.NEW & NOTEWORTHY We present vessel density alterations in response to flicker stimulation using optical coherence tomography angiography and identified the superficial capillary plexus as the layer with the most pronounced effect. This points out the physiological importance of the microvasculature in mediating functional hyperemia and suggests a fine-tuned plexus-specific mechanism to meet cellular metabolic demands.

Endovascular Cerebral Venous Sinus Imaging with Optical Coherence Tomography.

Imaging of the cerebral venous sinuses has evolved Substantially during the past 2 decades, and most recently intravascular sinus imaging with sonography has shed light on the pathophysiology of sinus thrombosis and intracranial hypertension. Optical coherence tomography is the highest resolution intravascular imaging technique available but has not been previously used in cerebral sinus imaging. The purpose of this study was to develop a preclinical animal model of endovascular optical coherence tomography cerebral venous sinus imaging and compare optical coherence tomography findings with histology. Four consecutive Yorkshire swine were selected. The superior sagittal sinus was first catheterized with a microwire, and the optical coherence tomography catheter was delivered via a monorail technique into the sinus. Luminal blood was cleared with a single arterial injection. After structural and Doppler optical coherence tomography imaging, a craniotomy was performed and the sinus and adjacent dura/veins were resected. Bland-Altman analysis was performed to compare optical coherence tomography and histology. Technically successful optical coherence tomography images were obtained in 3 of 4 swine. The luminal environment and visualization of dural arteries and draining cortical veins were characterized. The average maximum diameters of the sinus, dural arteries, and cortical veins were 3.14 mm, 135 µm, and 260 µm, respectively. Bland-Altman analysis demonstrated good agreement between histology and optical coherence tomography images. Endovascular optical coherence tomography imaging was feasible in this preclinical animal study. Adoption of this imaging technique in the human cerebral venous sinus could aid in the diagnosis, treatment, and understanding of the pathophysiology of various diseases of the sinus. Human safety and feasibility studies are needed.

Embryonic Mouse Cardiodynamic OCT Imaging.

The embryonic heart is an active and developing organ. Genetic studies in mouse models have generated great insight into normal heart development and congenital heart defects, and suggest mechanical forces such as heart contraction and blood flow to be implicated in cardiogenesis and disease. To explore this relationship and investigate the interplay between biomechanical forces and cardiac development, live dynamic cardiac imaging is essential. Cardiodynamic imaging with optical coherence tomography (OCT) is proving to be a unique approach to functional analysis of the embryonic mouse heart. Its compatibility with live culture systems, reagent-free contrast, cellular level resolution, and millimeter scale imaging depth make it capable of imaging the heart volumetrically and providing spatially resolved information on heart wall dynamics and blood flow. Here, we review the progress made in mouse embryonic cardiodynamic imaging with OCT, highlighting leaps in technology to overcome limitations in resolution and acquisition speed. We describe state-of-the-art functional OCT methods such as Doppler OCT and OCT angiography for blood flow imaging and quantification in the beating heart. As OCT is a continuously developing technology, we provide insight into the future developments of this area, toward the investigation of normal cardiogenesis and congenital heart defects.

Ophthalmic Artery and Superior Ophthalmic Vein Blood Flow Dynamics in Glaucoma Investigated by Phase Contrast Magnetic Resonance Imaging.

Ophthalmic artery (OA) and superior ophthalmic vein (SOV) blood flow were quantified by phase contrast magnetic resonance imaging (PC MRI) and seemed lower in glaucoma. Venous flow dynamics was different in glaucoma patients with a significantly decreased pulsatility. Studies using color Doppler imaging and optical coherence tomography flowmetry strongly suggested that vascular changes are involved in the pathophysiology of glaucoma, but the venous outflow has been little studied beyond the episcleral veins. This study measured the OA and the SOV flow by PC MRI in glaucoma patients compared with controls. Eleven primary open-angle glaucoma patients, with a mean±SD visual field deficit of -2.3±2.7 dB and retinal nerve fiber layer thickness of 92±13 µ, and 10 controls of similar age, were examined by PC MRI. The mean, maximal and minimal flow over cardiac cycle were measured. The variation of flow (ΔQ) was calculated. The OA mean±SD mean flow was 13.21±6.79 in patients and 15.09±7.62 mL/min in controls (P=0.35) and the OA maximal flow was 25.70±12.08 mL/min in patients, and 28.45±10.64 mL/min in controls (P=0.22). In the SOV the mean±SD mean flow was 6.46±5.50 mL/min in patients and 7.21±6.04 mL/min in controls (P=0.81) and the maximal flow was 9.06±6.67 in patients versus 11.96±9.29 mL/min in controls (P=0.47). The ΔQ in the SOV was significantly lower in patients (5.45±2.54 mL/min) than in controls (9.09±5.74 mL/min) (P=0.04). Although no significant difference was found, the mean and maximal flow in the OA and SOV seemed lower in glaucoma patients than in controls. The SOV flow waveform might be affected in glaucoma, corroborating the hypothesis of an impairment of venous outflow in those patients.

Semi-automated shear stress measurements in developing embryonic hearts.

Blood-induced shear stress influences gene expression. Abnormal shear stress patterns on the endocardium of the early-stage heart tube can lead to congenital heart defects. To have a better understanding of these mechanisms, it is essential to include shear stress measurements in longitudinal cohort studies of cardiac development. Previously reported approaches are computationally expensive and nonpractical when assessing many animals. Here, we introduce a new approach to estimate shear stress that does not rely on recording 4D image sets and extensive post processing. Our method uses two adjacent optical coherence tomography frames (B-scans) where lumen geometry and flow direction are determined from the structural data and the velocity is measured from the Doppler OCT signal. We validated our shear stress estimate by flow phantom experiments and applied it to live quail embryo hearts where observed shear stress patterns were similar to previous studies.

A deep-learning-based approach for noise reduction in high-speed optical coherence Doppler tomography.

Optical coherence Doppler tomography (ODT) increasingly attracts attention because of its unprecedented advantages with respect to high contrast, capillary-level resolution and flow speed quantification. However, the trade-off between the signal-to-noise ratio of ODT images and A-scan sampling density significantly slows down the imaging speed, constraining its clinical applications. To accelerate ODT imaging, a deep-learning-based approach is proposed to suppress the overwhelming phase noise from low-sampling density. To handle the issue of limited paired training datasets, a generative adversarial network is performed to implicitly learn the distribution underlying Doppler phase noise and to generate the synthetic data. Then a 3D based convolutional neural network is trained and applied for the image denoising. We demonstrate this approach outperforms traditional denoise methods in noise reduction and image details preservation, enabling high speed ODT imaging with low A-scan sampling density.

Cerebral tissue pO2 response to treadmill exercise in awake mice

We exploited two-photon microscopy and Doppler optical coherence tomography to examine the cerebral blood flow and tissue pO2 response to forced treadmill exercise in awake mice. To our knowledge, this is the first study performing both direct measure of brain tissue pO2 during acute forced exercise and underlying microvascular response at capillary and non-capillary levels. We observed that cerebral perfusion and oxygenation are enhanced during running at 5 m/min compared to rest. At faster running speeds (10 and 15 m/min), decreasing trends in arteriolar and capillary flow speed were observed, which could be due to cerebral autoregulation and constriction of arterioles in response to blood pressure increase. However, tissue pO2 was maintained, likely due to an increase in RBC linear density. Higher cerebral oxygenation at exercise levels 5–15 m/min suggests beneficial effects of exercise in situations where oxygen delivery to the brain is compromised, such as in aging, atherosclerosis and Alzheimer Disease.

Morphological and hemodynamic changes of sciatic nerves and their vasa nervorum during circular compression and relaxation

The main aim of this study was to evaluate the biomechanical and hemodynamic responses of vasa nervorum under transverse circular compression. In situ compress-and-hold experiments were performed on the sciatic nerves of healthy and diabetic rats, and the blood flow within the vasa nervorum was observed using Doppler-optical coherence tomography. A new technique was developed to obtain the time-course of the cross sectional area and the morphology of the vasa nervorum from the tomographic images. A quasi-linear viscoelastic model was used to investigate the overall biomechanical properties of the nerves, and a two-dimensional three-layered finite element model was constructed to analyze the distribution of stress and the morphological changes during the compression-relaxation process.The results showed that the lumenal area of vasa nervorum was reduced in the compression stage, especially for the diabetic nerves. The reduction was greater than 70% when the reduction of the nerve diameter was only 10%. The quasi-linear viscoelastic model showed that normal nerves were more elastic but less viscous than the diabetic nerves. The finite element analyses demonstrated that perineurium could sustain more stress than other layers, while epineurium served as a cushion to protect vasa nervora. In addition, there were regions within epineurium with less stress, so that vasa nervora in these saddle regions were less deformed. The vasa nervorum in diabetic rats was more prone to compression and reduction of blood flow than that of the normal rats. The histological studies supported the simulation results.

Repeatability and Reproducibility of Total Retinal Blood Flow Measurements Using Bi-Directional Doppler OCT.

PurposeTo investigate the repeatability and reproducibility of total retinal blood flow measurements using a custom-built dual-beam bidirectional Doppler optical coherence tomography (OCT) system in healthy subjects.MethodsRepeatability and reproducibility were analyzed in 10 and 34 healthy subjects, respectively. For repeatability, measurements were taken twice within 30 minutes, for reproducibility, twice within two to five weeks. Two analysis approaches were compared for calculation of absolute blood velocities: a previously published approach resulting in values for total arterial (QA,abs) and total venous blood flow (QV,abs) and a novel approach taking into account that there is a fixed relation between the phase shift in the two OCT channels (QA,new, QV,new). Repeatability and reproducibility were quantified using intraclass correlation coefficients (ICCs).ResultsFor QA,abs and QV,abs, ICC values between 0.78 and 0.84 were obtained. QA,new and QV,new values revealed better repeatability and reproducibility as compared to the convential appoach. Repeatability ICCs for QA,new and QV,new were between 0.91 and 0.93, and reproducibility ICCs were between 0.87 and 0.91 indicating excellent reproducibility. Good agreement was observed between total retinal blood flow values as measured from retinal arteries and retinal veins.ConclusionsMeasurement of total retinal blood flow using dual-beam Doppler OCT shows excellent reproducibility, which can further be improved by using a novel algorithm for calculating blood velocities in retinal vessels.Translational RelevanceOur data indicate that dual-beam Doppler OCT can be used for longitudinal studies. Hence, quantitative retinal blood flow may be established as a biomarker for progression vascular eye diseases.

Deterioration of Retinal Blood Flow Parameters in Branch Retinal Vein Occlusion Measured by Doppler Optical Coherence Tomography Flowmeter.

Background: Doppler optical coherence tomography (DOCT) flowmeter can be used to measure retinal blood flow (RBF) parameters, including vessel diameter, blood velocity, and the absolute value of RBF within 2.0 s. We investigated the RBF parameters in eyes with branch retinal vein occlusion (BRVO) using a DOCT flowmeter. Methods: Seventeen patients with unilateral BRVO were enrolled. All subjects underwent comprehensive ophthalmologic examinations. The RBF parameters were assessed from three veins, i.e., (1) an occluded vein, (2) a non-occluded vein in the BRVO eyes, and (3) an equivalent (superior or inferior) vein in the fellow eye (non-affected vein), using prototype DOCT flowmeter (Topcon, Tokyo, Japan). Moreover, the correlation between RBF parameters and the best corrected visual acuity (BCVA) was examined. We investigated the correlation between (1) the RBF parameters and the time from the initial visit, (2) the RBF parameters and the time from the last injection, and (3) the RBF parameters and the number of anti-vascular endothelial growth factor injections (VEGF). Results: The diameter of the occluded vein (95.9 ± 24.7 µm) was smaller than that of the non-occluded vein (127.9 ± 23.7 µm) and that of the healthy veins (116.4 ± 13.9 µm). The RBF was lower in the occluded veins (4.7 ± 3.7 µL/min) than that in the non-occluded veins (10.3 ± 5.1 µL/min; p < 0.01) and in the fellow eyes (8.6 ± 4.0 µL/min; p = 0.013). In contrast, the blood velocity was not significantly different among the three types of veins. BCVA was correlated with the diameter of the occluded vein (ρ = 0.711, p = 0.001) but not with the RBF and blood velocity. The time from the initial visit, the time from the last injection, and the total number of anti-VEGF injections were not associated with any RBF parameters on the occluded vein. Conclusions: The RBF was significantly lower in the occluded veins than that in the other veins, and the diameter of the occluded vein was significantly smaller than that of the other veins in patients with BRVO. However, neither the time from the initial visit, nor the time from the last injection, nor the number of anti-VEGF injections were correlated with the RBF parameters on the occluded vein.

9.4 MHz A-line rate optical coherence tomography at 1300\u2009nm using a wavelength-swept laser based on stretched-pulse active mode-locking

In optical coherence tomography (OCT), high-speed systems based at 1300 nm are among the most broadly used. Here, we present 9.4 MHz A-line rate OCT system at 1300 nm. A wavelength-swept laser based on stretched-pulse active mode locking (SPML) provides a continuous and linear-in-wavenumber sweep from 1240 nm to 1340 nm, and the OCT system using this light source provides a sensitivity of 98 dB and a single-sided 6-dB roll-off depth of 2.5 mm. We present new capabilities of the 9.4 MHz SPML-OCT system in three microscopy applications. First, we demonstrate high quality OCTA imaging at a rate of 1.3 volumes/s. Second, by utilizing its inherent phase stable characteristics, we present wide dynamic range en face Doppler OCT imaging with multiple time intervals ranging from 0.25 ms to 2.0 ms at a rate of 0.53 volumes/s. Third, we demonstrate video-rate 4D microscopic imaging of a beating Xenopus embryo heart at a rate of 30 volumes/s. This high-speed and high-performance OCT system centered at 1300 nm suggests that it can be one of the most promising high-speed OCT platforms enabling a wide range of new scientific research, industrial, and clinical applications at speeds of 10 MHz.

Label-free assessment of hemodynamics in individual cortical brain vessels using third harmonic generation microscopy.

We show that third harmonic generation (THG) microscopy using a 1-MHz train of 1,300-nm femtosecond duration laser pulses enabled visualization of the structure and quantification of flow speed in the cortical microvascular network of mice to a depth of > 1 mm. Simultaneous three-photon imaging of an intravascular fluorescent tracer enabled us to quantify the cell free layer thickness. Using the label-free imaging capability of THG, we measured flow speed in different types of vessels with and without the presence of an intravascular tracer conjugated to a high molecular weight dextran (2 MDa FITC-dextran, 5% w/v in saline, 100 µl). We found a ∼20% decrease in flow speeds in arterioles and venules due to the dextran-conjugated FITC, which we confirmed with Doppler optical coherence tomography. Capillary flow speeds did not change, although we saw a ∼7% decrease in red blood cell flux with dextran-conjugated FITC injection.

Doppler optical coherence tomography for energy seal evaluation and comparison to visual evaluation (Erratum).

.The erratum corrects a misspelled author surname.

Retinal blood flow reduction in normal-tension glaucoma with single-hemifield damage by Doppler optical coherence tomography

AimsTo evaluate the associations between retinal blood flow (RBF) and optical coherence tomography (OCT) structural measurements in normal-tension glaucoma (NTG) eyes with single-hemifield visual field (VF) damage by the Doppler...

Anatomical and functional changes in the retina in patients with Alzheimer's disease and mild cognitive impairment.

PurposeThere is evidence that mild cognitive impairment (MCI) or Alzheimer's disease (AD) is accompanied by alterations in the retina. The current study was performed to investigate structural and functional changes in patients with systemic neurodegenerative disease.MethodsA total of 47 patients with either MCI or AD and 43 healthy age‐ and sex‐matched control subjects were included. Inclusion criteria for MCI were abnormal memory function and a mini‐mental state examination (MMSE) score >26 points, for patients with AD a diagnosis of probable AD of mild to moderate degree and an MMSE score in the range of 20–26. Retinal blood flow was measured using a Doppler optical coherence tomography (OCT) system. Retinal vessel diameter, oxygen saturation and flicker‐induced vasodilatation were measured using a Vessel Analyzer. Retinal nerve fibre layer thickness (RNFLT) was assessed using an OCT system.ResultsGlobal RNFLT was lower in patients compared to healthy controls (93.7 ± 12.8 µm versus 99.1 ± 9.0 µm, p = 0.02). The same was found in regards to retinal arterial blood flow, which was 9.3 ± 2.4 and 12.3 ± 3.2 μl/min in the patient and control groups, respectively (p < 0.001). Mean retinal arterial diameter was reduced in patients (76.0 ± 8.9 µm versus 80.6 ± 8.0 µm, p = 0.03). Arteriovenous difference in oxygen saturation was lower in patients (20.4 ± 5.1% versus 23.5 ± 4.0%, p < 0.01). No difference in the flicker response was observed.ConclusionIn patients with MCI and AD, arteriovenous difference in oxygen saturation, retinal blood flow and arterial vessel diameter was reduced. No difference was found in flicker response between groups. This indicates alterations in retinal oxygen metabolism in patients with neurodegenerative disease.

Functional optical coherence tomography and photoacoustic microscopy imaging for zebrafish larvae.

We present a dual modality functional optical coherence tomography and photoacoustic microscopy (OCT-PAM) system. The photoacoustic modality employs an akinetic optical sensor with a large imaging window. This imaging window enables direct reflection mode operation, and a seamless integration of optical coherence tomography (OCT) as a second imaging modality. Functional extensions to the OCT-PAM system include Doppler OCT (DOCT) and spectroscopic PAM (sPAM). This functional and non-invasive imaging system is applied to image zebrafish larvae, demonstrating its capability to extract both morphological and hemodynamic parameters in vivo in small animals, which are essential and critical in preclinical imaging for physiological, pathophysiological and drug response studies.