Doppler Optical Coherence Tomography Research Articles

Investigating spontaneous retinal venous pulsation using Doppler optical coherence tomography

We demonstrate the advantages of optical coherence tomography (OCT) imaging for investigation of spontaneous retinal venous pulsation (SRVP). The pulsatile changes in venous vessel caliber are analyzed qualitatively and quantitatively using conventional intensity-based OCT as well as the functional extension Doppler OCT (DOCT). Single-channel and double-channel line scanning protocols of our multi-channel OCT prototype are employed to investigate venous pulsatile caliber oscillations as well as venous flow pulsatility in the eyes of healthy volunteers. A comparison to recordings of scanning laser ophthalmoscopy (SLO) – a standard en-face imaging modality for evaluation of SRVP – is provided, emphasizing the advantages of tomographic image acquisition. To the best of our knowledge, this is the first quantitative time-resolved investigation of SRVP and associated retinal perfusion characteristics using OCT.

Automatic boundary segmentation of vascular Doppler optical coherence tomography images based on cascaded U-net architecture

Doppler optical coherence tomography (OCT) imaging of vessels after anastomosis procedures can provide high resolution structure and blood flow imaging of the vessel simultaneously for objective surgical evaluation. Automatic boundary segmentation of the outer vessel wall boundary and its inner lumen contour is a very crucial and fundamental step for the responsive and complicated quantitative analysis required in future clinical applications of Doppler OCT imaging. In this work, we proposed a cascaded U-net (CU-net) architecture to segment the vascular intensity image and its corresponding phase image for the outer vessel wall boundary and the inner blood flowing lumen contour, respectively. CU-net architecture was developed by training two specific U-net frameworks in coordination: the first performs intensity image segmentation while the second performs phase image segmentation. Output of the first framework was sent to the input of the second framework as a mask to select area of interests. Model training time can be reduced effectively by cascading two U-net frameworks. Testing segmentation accuracy for outer vessel wall boundary and inner lumen contour were calculated to be 96.7%±0.2% and 94.8%±0.2%, respectively. The CU-net architecture requires no pre-processing on noises inherent with OCT images, such as random noise and speckle noise. The segmentation was automatic and end-to-end. 250 Doppler OCT images from one in-vivo mouse femoral artery imaging were successfully segmented automatically with an average processing time of 0.68s including both the outer vessel boundary and inner lumen contour. Thrombosis morphology, the inner blood flowing lumen area, and its radius variation were quantitatively analyzed based on the segmentation results, demonstrating the potential for clinical objective evaluation.

Artifacts in speckle tracking and multi-aperture Doppler OCT imaging of lateral motion.

In optical coherence tomography (OCT), lateral motion is determined either by speckle tracking or by multi-aperture Doppler OCT. Here we show that both methods may provide incorrect results because, outside the focal plane, non-uniform axial motion is misinterpreted as lateral motion. First, we demonstrate the existence of this artifact by means of a simulation for speckle tracking. Then the physical origin of the artifact and its mathematical relation to defocus and axial motion are explained. It is shown that speckle tracking and multi-aperture Doppler OCT are equally affected by the artifact, which has a considerable effect, even for a defocus of less than one Rayleigh length.

Computationally effective 2D and 3D fast phase unwrapping algorithms and their applications to Doppler optical coherence tomography.

We propose a simplification for a robust and easy to implement fast phase unwrapping (FPU) algorithm that is used to solve the phase wrapping problem encountered in various fields of optical imaging and metrology. We show that the number of necessary computations using the algorithm can be reduced compared to its original version. FPU can be easily extended from two to three spatial dimensions. We demonstrate the applicability of the two- and three-dimensional FPU algorithm for Doppler optical coherence tomography (DOCT) in numerical simulations, and in the imaging of a flow phantom and blood flow in the human retina in vivo. We introduce an FPU applicability plot for use as a guide in the selection of the most suitable version of the algorithm depending on the phase noise in the acquired data. This plot uses the circular standard deviation of the wrapped phase distribution as a measure of noise and relates it to the root-mean-square error of the recovered, unwrapped phase.

Boundary segmentation based on modified random walks for vascular Doppler optical coherence tomography images

Vascular Doppler optical coherence tomography (DOCT) images with weak boundaries are usually difficult for most algorithms to segment. We propose a modified random walk (MRW) algorithm with a novel regularization for the segmentation of DOCT vessel images. Based on MRW, we perform automatic boundary detection of the vascular wall from intensity images and boundary extraction of the blood flowing region from Doppler phase images. Dice, sensitivity, and specificity coefficients were adopted to verify the segmentation performance. The experimental study on DOCT images of the mouse femoral artery showed the effectiveness of our proposed method, yielding three-dimensional visualization and quantitative evaluation of the vessel.

基于差分相位解析的复频域多普勒光学相干层析成像技术

基于差分相位解析的复频域多普勒光学相干层析成像技术

Basic study on Micro-tomographic Visualizing System of Pharmacokinetics by Photo-Thermal Doppler OCT (PT-OCDV)

Basic study on Micro-tomographic Visualizing System of Pharmacokinetics by Photo-Thermal Doppler OCT (PT-OCDV)

Endoscopic optical coherence tomography with wide field-of-view for the morphological and functional assessment of the human tympanic membrane.

.An endoscopic optical coherence tomography (OCT) system with a wide field-of-view of 8 mm is presented, which combines the image capability of endoscopic imaging at the middle ear with the advantages of functional OCT imaging, allowing a morphological and functional assessment of the human tympanic membrane. The endoscopic tube has a diameter of 3.5 mm and contains gradient-index optics for simultaneous forward-viewing OCT and video endoscopy. The endoscope allows the three-dimensional visualization of nearly the entire tympanic membrane. In addition, the oscillation of the tympanic membrane is measured spatially resolved and in the frequency range between 500 Hz and 5 kHz with 125 Hz resolution, which is realized by phase-resolved Doppler OCT imaging during acoustical excitation with chirp signals. The applicability of the OCT system is demonstrated in vivo. Due to the fast image acquisition, structural and functional measurements are only slightly affected by motion artifacts.

Perspective: Current challenges and solutions of Doppler optical coherence tomography and angiography for neuroimaging

The nervous system, based on a complex network of nerves and cells, carries messages by transmitting signals to and from different parts of the body. The supply of blood flow in the nervous system is critical to maintain physiological functions. Optical coherence tomography (OCT) has the ability to noninvasively image the microvascular networks and accurately quantify the blood flow in vivo with high spatial and temporal resolutions in three dimensions. It has been used to measure changes in blood supplies and assess physiological functions before and after occurrences of diseases, drug administration, and external stimulation in the nervous system, especially in the brain. In this paper, we discuss current challenges of Doppler OCT and angiography in the data processing algorithms and imaging systems for neuroscience research. The advancements and feasible solutions for current challenges are proposed.

Buffer-averaging super-continuum source based spectral domain optical coherence tomography for high speed imaging.

In super-continuum (SC) source based spectral domain optical coherence tomography (SC-SDOCT), the stability of the power spectral density (PSD) has a significant impact on OCT system sensitivity and image signal to noise ratio (SNR). High speed imaging decreases the camera's exposure time, thus each A-scan contained fewer laser pulse excited SC wideband emissions, resulting in a decrease of SNR. In this manuscript, we present a buffer-averaging SC-SDOCT (BASC-SDOCT) to improve the system's performance without losing imaging speed, taking advantage of the excess output power from typical SC sources. In our proposed technique, the output light from SC was passed through a fiber based light buffering and averaging system to improve the PSD stability by averaging 8 SC emissions. The results showed that 6.96 µs of SC emission after buffering and averaging can achieve the same PSD stability equivalent to a longer exposure time of 55.68 µs, despite increasing the imaging speed from 16.8 kHz to 91.9 kHz. The system sensitivity was improved by 8.6 dB, reaching 100.6 dB, which in turn improved SNR of structural imaging, Doppler OCT velocity measurement, and speckle variance OCT (SVOCT) angiographic imaging as demonstrated by phantom and in vivo experiments.

Multimodal Optical Medical Imaging Concepts Based on Optical Coherence Tomography

Optical medical imaging techniques in general exhibit outstanding resolution and molecule-specific contrast. They come however with a limited penetration in depth and small field of view. Multimodal concepts help to combine complementary strengths of different imaging technologies. The present article reviews the advantages of optical multimodal imaging concepts using optical coherence tomography (OCT) as core technology. In particular we first discuss polarization sensitive OCT, Doppler OCT and OCT angiography, OCT elastography and spectroscopic OCT as intramodal concepts. To highlight intermodal imaging concepts, we then chose the combination of OCT with photoacoustics, and with non-linear optical microscopy. The selected multimodal concepts and their particular complementary strengths and applications are discussed in detail. The article concludes with notes on standardization of OCT imaging and multimodal extensions.

Doppler OCT clutter rejection using variance minimization and offset extrapolation.

Doppler optical coherence tomography (OCT) is widely used for high-resolution mapping of flow velocities and is based on analysis of temporal changes in the phase of an OCT signal (i.e., how fast the OCT signal rotates in the complex plane). Determination of the rate of phase change or rotation speed critically depends on the center of rotation. Here, we demonstrate the bias in high-pass filtering, the current widely used method to determine the center of rotation, and propose two advanced methods for Doppler OCT clutter rejection. The bias in the high-pass filtering method becomes increasingly significant with lower velocities or larger signal noise. Two novel methods based on variance minimization and offset extrapolation can potentially reduce this bias and thereby improve the accuracy of Doppler OCT measurements of flow velocities, even for low-velocity and/or high-noise signals. The two novel methods and the current standard method (high-pass filtering) have been tested in combination with several currently used velocity measurement algorithms: Kasai, autocorrelation function fitting, and maximum likelihood estimation. The newly proposed methods are shown to improve the accuracy in both the center of rotation and resultant velocity by up to 60 percentage points and reduce the flow conservation error by 30% when applied to in vivo cerebral blood flow imaging of the rodent brain cortex.

The Retinal Oxygen Saturation Measured by Dual Wavelength Oximetry in Larger Retinal Vessels is Influenced by the Linear Velocity of the Blood

ABSTRACTPurpose: Dual wavelength retinal oximetry allows the quantification of oxygen saturation in the larger retinal vessels. However, the technique might be refined further by identifying factors that are responsible for the different oxygen saturations in first order arterioles from the same eye shortly after their branching from the central retinal artery. The purpose of the present study is to investigate whether these factors involve rheological characteristics in the studied vessels.Materials and Methods: In fourty healthy persons the oxygen saturation was measured by dual wavelength oximetry and the blood flow by Doppler OCT in the upper and lower temporal and nasal arterioles and venules shortly after their branching from the central retinal artery and vein. The relationship of the measured oxygen saturations with age, vessel diameter, and blood linear velocity were assessed.Results: The measured oxygen saturations were (mean± SD) 97.8% ± 6.4% in the arterioles and 60.2% ± 8.8% in the venules. For both the arterioles and the venules the measured oxygen saturation (Sm) correlated significantly with the linear velocity (v) of the blood in mm/s (Sm = 101.6–0.28*v, p < 0.0001 for arterioles and Sm = 64.5–0.38*v, p = 0.002 for venules). After correction for the variation in linear velocity, the differences in saturation between first order branches from both arterioles and venules were significantly reduced and the standard deviation of the oxygen saturations were reduced to less than one third.Conclusions: Measurements of oxygen saturation in larger retinal arterioles and venules using dual wavelength oximetry can be improved by correcting for the influence of the linear velocity of the blood.

Intravital imaging of adriamycin-induced renal pathology using two-photon microscopy and optical coherence tomography

Adriamycin (doxorubicin), a common cancer chemotherapeutic drug, can be used to induce a model of chronic progressive glomerular disease in rodents. In our studies, we evaluated renal changes in a rat model after Adriamycin injection using two-photon microscopy (TPM), optical coherence tomography (OCT) and Doppler OCT (DOCT). Taking advantage of deep penetration and fast scanning speed for three-dimensional (3D) label-free imaging, OCT/DOCT system was able to reveal glomerular and tubular pathology noninvasively and in real time. By imaging renal pathology following the infusion of fluorophore-labeled dextrans of different molecular weights, TPM can provide direct views of glomerular and tubular flow dynamics with the onset and progression of renal disease. Specifically, glomerular permeability and filtration, proximal and distal tubular flow dynamics can be revealed. 6–8 weeks after injection of Adriamycin, TPM and OCT/DOCT imaging revealed glomerular sclerosis, compromised flow across the glomerular wall, tubular atrophy, tubular dilation, and variable intra-tubular flow dynamics. Our results indicate that TPM and OCT/DOCT provide real-time imaging of renal pathology in vivo that has not been previously available using conventional microscopic procedures.

Comparative Study of Optical Coherence Tomography Angiography and Phase-Resolved Doppler Optical Coherence Tomography for Measurement of Retinal Blood Vessels Caliber.

PurposeTo compare the accuracy of Doppler optical coherence tomography (DOCT) and OCT angiography (OCTA) for measuring retinal blood vessel caliber at different flow rates.MethodsA research-grade 1060-nm OCT system with 3.5-μm axial resolution in retinal tissue and 92,000 A scan/s image acquisition rate was used in this study. DOCT and OCTA measurements were acquired both from a flow phantom and in vivo from retinal blood vessels in six male Brown Norway rats. The total retinal blood flow (TRBF) was modified from baseline to 70% and 20% of baseline by reducing the ocular perfusion pressure (OPP). The retinal blood vessel caliber (RBVC) was measured from OCTA and DOCT images. The caliber measurements were conducted by two separate graders using a custom MATLAB-based image processing algorithm.ResultsThe RBVC measured with OCTA and DOCT for normal blood flow rates were not significantly different (56.69 ± 12.17 and 57.17 ± 9.46 μm, P = 0.27, respectively). However, significant differences were detected when TRBF was reduced to 70% (55.69 ± 11.56 vs. 50.62 ± 8.85 μm, P < 0.01) and 20% (50.29 ± 9.29 vs. 44.88 ± 7.13 μm, P < 0.01) of baseline.ConclusionsReduced TRBF resulted in inaccuracy of the RBVC measurements with DOCT in both the phantom and animal study. This result suggests that OCTA is a more accurate tool for RBVC evaluation when applied to retinal diseases associated with reduced TRBF, such as glaucoma and diabetic retinopathy.Translational RelevanceResults from this study are directly applicable to clinical studies of retinal blood flow measured with OCTA and DOCT.

In Vivo Vibration Measurement of Middle Ear Structure Using Doppler Optical Coherence Tomography: Preliminary Study.

Objectives Doppler optical coherence tomography (DOCT) is useful for both, the spatially resolved measurement of the tympanic membrane (TM) oscillation and high-resolution imaging. We demonstrated a new technique capable of providing real-time two-dimensional Doppler OCT image of rapidly oscillatory latex mini-drum and in vivo rat TM and ossicles.Methods Using DOCT system, the oscillation of sample was measured at frequency range of 1–4 kHz at an output of 15 W. After the sensitivity of the DOCT system was verified using a latex mini-drum consisting of a 100 μm-thick latex membrane, changes in displacement of the umbo and contacted area between TM and malleus in normal and pathologic conditions.Results The oscillation cycles of the mini-drum for stimulus frequencies were 1.006 kHz for 1 kHz, 2.012 kHz for 2kHz, and 3.912 kHz for 4 kHz, which means that the oscillation cycle of the mini-drum become short in proportional to the frequency of stimuli. The oscillation cycles of umbo area and the junction area in normal TM for frequencies of the stimuli showed similar integer ratio with the data of latex mini-drum for stimuli less than 4 kHz. In the case of middle ear effusion condition, the Doppler signal showed a tendency of attenuation in all frequencies, which was prominent at 1 kHz and 2 kHz.Conclusion The TM vibration under sound stimulation with frequencies from 1 kHz to 4 kHz in normal and pathologic conditions was demonstrated using signal demodulation method in in vivo condition. The OCT technology could be helpful for functional and structural assessment as an optional modality.

Interferometric detection of 3D motion using computational subapertures in optical coherence tomography.

Doppler optical coherence tomography (OCT) quantifies axial motion with high precision, whereas lateral motion cannot be detected by a mere evaluation of phase changes. This problem was solved by the introduction of three-beam Doppler OCT, which, however, entails a high experimental effort. Here, we present the numerical analogue to this experimental approach. Phase-stable complex-valued OCT datasets, recorded with full-field swept-source OCT, are filtered in the Fourier domain to limit imaging to different computational subapertures. These are used to calculate all three components of the motion vector with interferometric precision. As known from conventional Doppler OCT for axial motion only, the achievable accuracy exceeds the actual imaging resolution by orders of magnitude in all three dimensions. The feasibility of this method is first demonstrated by quantifying micro-rotation of a scattering sample. Subsequently, a potential application is explored by recording the 3D motion vector field of tissue during laser photocoagulation in ex-vivo porcine retina.

Measurement of flow-mediated dilation of mouse femoral artery in vivo by optical coherence tomography.

Flow-mediated vasodilation (FMD) is used for assessment of vascular endothelial function in humans as a predictor of cardiovascular events. It has been challenging to carry it on preclinical murine models due to the diminutive size of the femoral artery. Here, we present a new approach to accurately measure the blood velocity and femoral artery diameters of mice by acquiring Doppler optical coherence tomography and optical coherence tomography angiography continuously within 1 single experimental scanning protocol. Using the 3-dimensional imaging and new velocity algorithm, the measurement precision of diameter, blood flow, velocity and wall shear stress are improved to 0.91%, 11.0%, 10.7% and 14.0%, respectively. FMD of healthy mouse femoral artery measured by this method was 11.96% ± 0.98%, which was blunted to 5.69% ± 0.4% by intravenous administration of endothelial nitric oxide synthase inhibitor (L-NG -Nitroarginine methyl ester), in agreement with that reported in the literature.

Adaptable switching schemes for time-encoded multichannel optical coherence tomography.

We introduce the approach of variable time encoding for multichannel optical coherence tomography (OCT). High-speed fiber optical switches are applied for sequential sample arm switching to enable quasisimultaneous image acquisition from three different orientation angles. In comparison with previous multichannel OCT (using simultaneous sample illumination), time-encoded multichannel OCT has no need for division of illumination power among the respective channels to satisfy laser safety requirements. Especially for ophthalmic applications-in particular retinal imaging, which the presented prototype was developed for-this advantage strongly influences image quality through an enhanced sensitivity. Nevertheless, time encoding comes at the cost of a decrease in imaging speed due to sequential channel illumination. For the typical multichannel OCT modality Doppler OCT, this results in a reduction of the maximum unambiguously determinable Doppler velocity. However, we demonstrate that this drawback can be overcome by adaptation of the illumination channel switching scheme. Thus, a re-extension of the maximum unambiguously determinable Doppler frequency to the full A-scan rate of the tunable light source is presented. The performance of the technique is demonstrated by flow phantom experiments and measurements of retinal blood flow in the eyes of healthy human volunteers.

Quantitative hemodynamic analysis of cerebral blood flow and neurovascular coupling using optical coherence tomography angiography

Functional hyperemia in the rat cortex was investigated using high-speed optical coherence tomography (OCT) angiography and Doppler OCT. OCT angiography (OCTA) was performed to image the hemodynamic stimulus-response over a wide field of view. Temporal changes in vessel diameters in different vessel compartments, which were determined as the diameters of erythrocyte flows in OCT angiograms, were measured in order to monitor localized hemodynamic changes. Our results showed that the dilation of arterioles at the site of activation was accompanied by the dilation of upstream arteries. Relatively negligible dilation was observed in veins. An increase in the OCTA signal was observed during stimulus in multiple capillaries, which may imply that capillary blood flow increases as a result of the expanded arterial blood volume. These results agree with previous observations using two-photon laser scanning microscopy (TPLSM). Doppler OCT was performed to quantitatively measure stimulus-induced blood flow response in pial arteries. The measurement showed small but clear hemodynamic response in upstream arteries with diameters exceeding 100 m. Our results demonstrate the potential of OCTA and Doppler OCT for the investigation of neurovascular coupling in small animal models.