Phase-resolved Doppler Optical Coherence Research Articles

Noncontact longitudinal shear wave imaging for the evaluation of heterogeneous porcine brain biomechanical properties using optical coherence elastography.

High-resolution quantification of heterogeneous brain biomechanical properties has long been an important topic. Longitudinal shear waves (LSWs) can be used to assess the longitudinal Young's modulus, but contact excitation methods have been used in most previous studies. We propose an air-coupled ultrasound transducer-based optical coherence elastography (AcUT-OCE) technique for noncontact excitation and detection of LSWs in samples and assessment of the nonuniformity of the brain's biomechanical properties. The air-coupled ultrasonic transducer (AcUT) for noncontact excitation of LSWs in the sample has a center frequency of 250 kHz. Phase-resolved Doppler optical coherence tomography (OCT) was used to image and reconstruct the propagation behavior of LSWs and surface ultrasound waves at high resolution. An agar phantom model was used to verify the feasibility of the experimental protocol, and experiments with ex vivo porcine brain samples were used to assess the nonuniformity of the brain biomechanical properties. LSWs with velocities of 0.83 ± 0.11 m/s were successfully excited in the agar phantom model. The perivascular elastography results in the prefrontal cortex (PFC) of the ex vivo porcine brains showed that the Young's modulus was significantly higher in the longitudinal and transverse directions on the left side of the cerebral vessels than on the right side and that the Young's modulus of the PFC decreased with increasing depth. The AcUT-OCE technique, as a new scheme for LSW applications in in vivo elastography, can be used for noncontact excitation of LSWs in brain tissue and high-resolution detection of heterogeneous brain biomechanical properties.

Autocorrelation analysis-based OCT velocimetry for axial blood flow velocity imaging of the cerebral capillary network.

The accurate measurement of blood flow velocity in the capillary network is challenging due to the small size of the vessels and the slow flow of red blood cells (RBCs) within the vessel. Here, we introduce an autocorrelation analysis-based optical coherence tomography (OCT) method that takes less acquisition time to measure the axial blood flow velocity in the capillary network. The axial blood flow velocity was obtained from the phase change in the decorrelation period of the first-order field autocorrelation function (g1) of the OCT field data, which was acquired with M-mode acquisition (repeated A-scans). The rotation center of g1 in the complex plane was first re-centralized to the origin, then the phase change due to the movement of RBCs was extracted in the g1 decorrelation period which is usually 0.2-0.5 ms. In phantom experiments, the results suggest that the proposed method could accurately measure the axial speed with a wide range of 0.5-15 mm/s. We further tested the method on living animals. Compared with the phase-resolved Doppler optical coherence tomography (pr-DOCT), the proposed method can obtain robust axial velocity measurements with more than five times shorter acquisition time.

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.

Comparison of phase-resolved Doppler optical coherence tomography and optical coherence tomography angiography for measuring retinal blood vessels size

The goal of this study was to compare two OCT-based methods for measuring retinal blood vessels size: Phase-resolved Doppler OCT (DOCT) and OCT angiography (OCTA). The study was conducted in rats (n= 6) using a SD-OCT system operating at 1060 nm with 92 kHz image acquisition rate. Arteries and veins were separated by the phase polarity. Results from this study showed that the venal diameters are significantly larger than the arterial diameters, and there is no significant difference in the vessel diameters measured by both methods.

Visualization and Detection of Ciliary Beating Pattern and Frequency in the Upper Airway using Phase Resolved Doppler Optical Coherence Tomography

Ciliary motion plays a critical role in the overall respiratory health of the upper airway. These cilia beat at a native frequency and in a synchronized pattern to continuously transport foreign particulate trapped in a layer of mucous out of the upper airway. Disruption of ciliary motion can lead to severe respiratory diseases and compromised respiratory function. Currently, the study of cilia requires expensive high speed cameras and high powered microscopes which is unsuitable for in vivo imaging and diagnosis. Doppler based optical coherence tomography has the potential to visualize the microscopic motion of cilia during their beating cycle. We demonstrate the development of a high-speed Doppler optical coherence tomography system that not only can rapidly determine the cilia beat frequency, but also simultaneously visualize the temporal cilia beating pattern which plays critical roles in cilia function.

Phase-Resolved Doppler Optical Coherence Tomographic Features in Retinal Angiomatous Proliferation.

To study patients diagnosed with retinal angiomatous proliferation (RAP) based on conventional imaging techniques with phase-resolved Doppler optical coherence tomography (OCT) to detect and localize blood flow in RAP lesions; and to compare these findings to conventional imaging, which are mostly invasive and give limited information concerning intra- and transretinal blood flow. Single-center, consecutive observational case series. Twelve treatment-naïve patients diagnosed with RAP based on fundus examination, fluorescein angiography, and indocyanine green angiography were included. Median age was 79 years (range 65-90). Patients were imaged with an experimental 1040nm swept-source phase-resolved Doppler OCT instrument. Abnormal flow was defined as intraretinal neovascularization or retinal choroidal anastomosis. In 11 patients adequate phase-resolved Doppler OCT images were obtained showing abnormal blood flow in the RAP lesion. In 4 patients a retinal choroidal anastomosis was found, 3 patients showed intraretinal neovascularization connected with a pigment epithelial detachment, 2 patients showed only intraretinal neovascularization, and in 2 patients flow was limited to the subretinal or sub-retinal pigment epithelial space. Phase-resolved Doppler OCT is able to detect and localize abnormal blood flow within RAP lesions. Blood flow was mostly confined to the intraretinal structures with or without a connecting pigment epithelial detachment; in one-third of patients a retinal choroidal anastomosis was detected. The potential of angiography with phase-resolved Doppler OCT to accurately distinguish between normal and pathologic blood flow in addition to structural OCT data without invasive procedures will help to further elucidate both retinal andchoroidal vascular pathologies like RAP.

Direct Blood Flow Measurements in a Free RPE-Choroid Graft with Phase-Resolved Doppler OCT.

We directly demonstrated the revascularization in a free retinal pigment epithelium (RPE)-choroid graft with direct blood flow detection by experimental phase-resolved Doppler optical coherence tomography (PRD-OCT). Seven patients with age-related macular degeneration underwent an RPE-choroid graft translocation in a prospective institutional cohort study. Spectral domain optical coherence tomography (SD-OCT) was used to measure the revascularization stage. With PRD-OCT the presence of flow was imaged postoperatively. The PRD-OCT confirmed flow in three patients when SD-OCT indicated the afferent vessel ingrowth stage, and in all seven patients when the SD-OCT indicated the efferent vessel ingrowth stage. The PRD-OCT study was able to detect the presence of blood flow in a free RPE-choroid graft. The PRD-OCT findings directly confirmed the revascularization that was otherwise based on the more circumstantial evidence provided by SD-OCT images and angiography. The use of both techniques to monitor the revascularization process in a free graft in patients are an interesting example of replacing more invasive by noninvasive techniques. There is potential future use of PRD-OCT for the visualization of vascularization patterns in other pathologies.

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.

Visualization of microvasculature by dual-beam phase-resolved Doppler optical coherence tomography

We present a dual-beam Doppler optical coherence tomography system for visualizing the microvasculature within the retina. The sample arm beams from two identical spectral domain optical coherence tomography (SD-OCT) systems are combined such that there is a small horizontal offset between them at the retina. Thereby we record two tomograms which are slightly separated in time. Phase-resolved Doppler analysis is performed between these two data sets. This system allows blood capillary imaging with high flow sensitivity and variable velocity range. To demonstrate the performance of our system we present images of the microvascular network around the fovea and around the optic nerve head of the human eye.

Swept-source based, single-shot, multi-detectable velocity range Doppler optical coherence tomography

Phase-Resolved Doppler Optical Coherence Tomography (PR-DOCT) allows visualization and characterization of the location, direction, velocity, and profile of flow activity embedded in a static sample structure. The detectable Velocity Dynamic Range (VDR) of each particular PR-DOCT system is governed by a detectable Doppler phase shift, a flow angle, and an acquisition time interval used to determine the Doppler phase shift. In general, the lower boundary of the detectable Doppler phase shift is limited by the phase stability of the system, while the upper boundary is limited by the π phase ambiguity. For a given range of detectable Doppler phase shift, shortening the acquisition duration will increase not only the maximum detectable velocity but unfortunately also the minimum detectable velocity, which may lead to the invisibility of a slow flow. In this paper, we present an alternative acquisition scheme for PR-DOCT that extends the lower limit of the velocity dynamic range, while maintaining the maximum detectable velocity, hence increasing the overall VDR of PR-DOCT system. The essence of the approach is to implement a technique of multi-scale measurement to simultaneously acquire multiple VDRs in a single measurement. We demonstrate an example of implementation of the technique in a dual VDR DOCT, where two Doppler maps having different detectable VDRs were simultaneously detected, processed, and displayed in real time. One was a fixed VDR DOCT capable of measuring axial velocity of up to 10.9 mm/s without phase unwrapping. The other was a variable VDR DOCT capable of adjusting its detectable VDR to reveal slow flow information down to 11.3 μm/s. The technique is shown to effectively extend the overall detectable VDR of the PR-DOCT system. Examples of real time Doppler imaging of an African frog tadpole are demonstrated using the dual-VDR DOCT system.

Doppler optical micro-angiography for volumetric imaging of vascular perfusion in vivo

We propose a Doppler optical micro-angiography (DOMAG) method to image flow velocities of the blood flowing in functional vessels within microcirculatory tissue beds in vivo. The method takes the advantages of recently developed optical micro-angiography (OMAG) technology, in which the endogenous optical signals backscattered from the moving blood cells are isolated from those originated from the tissue background, i.e., the tissue microstructures. The phase difference between adjacent A scans of OMAG flow signals is used to evaluate the flow velocity, similar to phase-resolved Doppler optical coherence tomography (PRDOCT). To meet the requirement of correlation between adjacent A scans in using the phase resolved technique to evaluate flow velocity, an ideal tissue-sample background (i.e., optically homogeneous tissue sample) is digitally reconstructed to replace the signals that represent the heterogeneous features of the static sample that are rejected in the OMAG flow images. Because of the ideal optical-homogeneous sample, DOMAG is free from the characteristic texture pattern noise due to the heterogeneous property of sample, leading to dramatic improvement of the imaging performance. A series of phantom flow experiments are performed to evaluate quantitatively the improved imaging performance. We then conduct in vivo experiments on a mouse brain to demonstrate that DOMAG is capable of quantifying the flow velocities within cerebrovascular network, down to capillary level resolution. Finally, we compare the in vivo imaging performance of DOMAG with that of PRDOCT, and show that DOMAG delivers at least 15-fold increase over the PRDOCT method in terms of the lower limit of flow velocity that can be detected.

Statistical properties of phase-decorrelation in phase-resolved Doppler optical coherence tomography.

Decorrelation noise limits the ability of phase-resolved Doppler optical coherence tomography systems to detect smaller vessels exhibiting slower flow velocities, which limits the utility of the technique in many clinical and biological settings. An understanding of the statistical properties of decorrelation noise can aid in the optimal design of these systems and guide the development of noise mitigating strategies. In this work, the statistical properties of decorrelation noise are derived from the underlying statistics of the coherent imaging system and validated through comparison with empirical results and Monte Carlo modeling. Expressions for the noise distribution and the noise variance as a function of relevant imaging system parameters are given, and the implications of these results on both system and algorithm design are discussed.

Doppler optical microangiography improves the quantification of local fluid flow and shear stress within 3-D porous constructs

Traditional phase-resolved Doppler optical coherence tomography (DOCT) has been reported to have potential for characterizing local fluid flow within a microporous scaffold. In this work, we apply Doppler optical microangiography (DOMAG), a new imaging technique developed by combining optical microangiography (OMAG) with a phase-resolved method, for improved assessment of local fluid flow and its derived parameters, shear stress, and interconnectivity, within highly scattering porous constructs. Compared with DOCT, we demonstrate a dramatic improvement of DOMAG in quantifying flow-related properties within scaffolds in situ for functional tissue engineering.

Phase-resolved Doppler optical coherence tomography—limitations and improvements

We describe how the simple phase difference averaging causes a systematic bias in the velocity estimation obtained by phase-resolved Fourier domain optical coherence tomography (FdOCT). The magnitude of this bias depends on the signal-to-noise ratio as well as proximity of the measured velocity to the limits of the velocity range. We demonstrate the proper way of data processing, which enables obtaining velocity values free of this error. We validate the improved technique by measurements of flow velocity in glass capillaries, in human retinal vessels, and we compare the results with those obtained by standard phase-resolved FdOCT.

Phase-resolved optical frequency domain imaging

Phase-resolved Doppler optical coherence tomography has been used to image blood flow dynamics in various tissues using both time-domain and spectral-domain optical coherence tomography techniques. In this manuscript, we present phase-resolved Doppler imaging with a high-speed optical frequency domain imaging system. We demonstrate that by correcting for spurious timing-induced phase errors, excellent flow sensitivity can be achieved, limited only by the imaging signal-to-noise ratio. Conventional and Doppler images showing flow in an Intralipid phantom and in human skin are presented. Additionally, we demonstrate the ability of phase-resolved OFDI to measure high flow rates without the deleterious effects of fringe washout.