Gangjun Liu

Optical Coherence Tomography Angiography

Optical coherence tomography angiography (OCTA) is a noninvasive approach that can visualize blood vessels down to the capillary level. With the advent of high-speed OCT and efficient algorithms, practical OCTA of ocular circulation is now available to ophthalmologists. Clinical investigations that used OCTA have increased exponentially in the past few years. This review will cover the history of OCTA and survey its most important clinical applications. The salient problems in the interpretation and analysis of OCTA are described, and recent advances are highlighted.

Optimization of the split-spectrum amplitude-decorrelation angiography algorithm on a spectral optical coherence tomography system

The split-spectrum amplitude-decorrelation angiography algorithm was optimized on a spectral optical coherence tomography system using a flow phantom. The number of times the spectrum was split and the bandwidth of each split were adjusted to maximize the flow phantom decorrelation signal-to-noise ratio. The improvement in flow detection was then demonstrated with en face retinal angiograms. The optimized algorithm increased the detectable retinal microvascular flow and decreased the variability of the quantified vessel density in OCT retinal angiograms of healthy human subjects.

Automated motion correction using parallel-strip registration for wide-field en face OCT angiogram.

We propose an innovative registration method to correct motion artifacts for wide-field optical coherence tomography angiography (OCTA) acquired by ultrahigh-speed swept-source OCT (>200 kHz A-scan rate). Considering that the number of A-scans along the fast axis is much higher than the number of positions along slow axis in the wide-field OCTA scan, a non-orthogonal scheme is introduced. Two en face angiograms in the vertical priority (2 y-fast) are divided into microsaccade-free parallel strips. A gross registration based on large vessels and a fine registration based on small vessels are sequentially applied to register parallel strips into a composite image. This technique is extended to automatically montage individual registered, motion-free angiograms into an ultrawide-field view.

En face Doppler total retinal blood flow measurement with 70 kHz spectral optical coherence tomography.

Abstract. An automated algorithm was developed for total retinal blood flow (TRBF) using 70-kHz spectral optical coherence tomography (OCT). The OCT was calibrated for the transformation from Doppler shift to speed based on a flow phantom. The TRBF scan pattern contained five repeated volume scans (2×2  mm) obtained in 3 s and centered on central retinal vessels in the optic disc. The TRBF was calculated using an en face Doppler technique. For each retinal vein, blood flow was measured at an optimal plane where the calculated flow was maximized. The TRBF was calculated by summing flow in all veins. The algorithm tracked vascular branching so that either root or branch veins are summed, but never both. The TRBF in five repeated volumes were averaged to reduce variation due to cardiac cycle pulsation. Finally, the TRBF was corrected for eye length variation. Twelve healthy eyes and 12 glaucomatous eyes were enrolled to test the algorithm. The TRBF was 45.4±6.7  μl/min for healthy control and 34.7±7.6  μl/min for glaucomatous participants (p-value=0.01). The intravisit repeatability was 8.6% for healthy controls and 8.4% for glaucoma participants. The proposed automated method provided repeatable TRBF measurement.

Postprocessing algorithms to minimize fixed-pattern artifact and reduce trigger jitter in swept source optical coherence tomography.

We propose methods to align interferograms affected by trigger jitter to a reference interferogram based on the information (amplitude/phase) at a fixed-pattern noise location to reduce residual fixed-pattern noise and improve the phase stability of swept source optical coherence tomography (SS-OCT) systems. One proposed method achieved this by introducing a wavenumber shift (k-shift) in the interferograms of interest and searching for the k-shift that minimized the fixed-pattern noise amplitude. The other method calculated the relative k-shift using the phase information at the residual fixed-pattern noise location. Repeating this wavenumber alignment procedure for all A-lines of interest produced fixed-pattern noise free and phase stable OCT images. A system incorporating these correction routines was used for human retina OCT and Doppler OCT imaging. The results from the two methods were compared, and it was found that the intensity-based method provided better results.

Calibration of optical coherence tomography angiography with a microfluidic chip

Abstract. A microfluidic chip with microchannels ranging from 8 to 96  μm was used to mimic blood vessels down to the capillary level. Blood flow within the microfluidic channels was analyzed with split-spectrum amplitude-decorrelation angiography (SSADA)-based optical coherence tomography (OCT) angiography. It was found that the SSADA decorrelation value was related to both blood flow speed and channel width. SSADA could differentiate nonflowing blood inside the microfluidic channels from static paper. The SSADA decorrelation value was approximately linear with blood flow velocity up to a threshold Vsat of 5.83±1.33  mm/s (mean±standard deviation over the range of channel widths). Beyond this threshold, it approached a saturation value Dsat. Dsat was higher for wider channels, and approached a maximum value Dsm as the channel width became much larger than the beam focal spot diameter. These results indicate that decorrelation values (flow signal) in capillary networks would be proportional to both flow velocity and vessel caliber but would be capped at a saturation value in larger blood vessels. These findings are useful for interpretation and quantification of clinical OCT angiography results.

Split-spectrum phase-gradient optical coherence tomography angiography

A phase gradient angiography (PGA) method is proposed for optical coherence tomography (OCT). This method allows the use of phase information to map the microvasculature in tissue without the correction of bulk motion and laser trigger jitter induced phase artifacts. PGA can also be combined with the amplitude/intensity to improve the performance. Split-spectrum technique can further increase the signal to noise ratio by more than two times. In-vivo imaging of human retinal circulation is shown with a 70 kHz, 840 nm spectral domain OCT system and a 200 kHz, 1050 nm swept source OCT system. Four different OCT angiography methods are compared. The best performance was achieved with split-spectrum amplitude and phase-gradient angiography.

SPECTRAL FRACTIONATION DETECTION OF GOLD NANOROD CONTRAST AGENTS USING OPTICAL COHERENCE TOMOGRAPHY

We demonstrate the proof of concept of a novel Fourier-domain optical coherence tomography contrast mechanism using gold nanorod contrast agents and a spectral fractionation processing technique. The methodology detects the spectral shift of the backscattered light from the nanorods by comparing the ratio between the short and long wavelength halves of the optical coherence tomography signal intensity. Spectral fractionation further divides the halves into sub-bands to improve spectral contrast and suppress speckle noise. Herein, we show that this technique can detect gold nanorods in intralipid tissue phantoms. Furthermore, cellular labeling by gold nanorods was demonstrated using retinal pigment epithelial cells in vitro.

Imaging the anterior eye with dynamic-focus swept-source optical coherence tomography

Abstract. A custom-built dynamic-focus swept-source optical coherence tomography (SS-OCT) system with a central wavelength of 1310 nm was used to image the anterior eye from the cornea to the lens. An electrically tunable lens was utilized to dynamically control the positions of focusing planes over the imaging range of 10 mm. The B-scan images were acquired consecutively at the same position but with different focus settings. The B-scan images were then registered and averaged after filtering the out-of-focus regions using a Gaussian window. By fusing images obtained at different depth focus locations, high-resolution and high signal-strength images were obtained over the entire imaging depth. In vivo imaging of human anterior segment was demonstrated. The performance of the system was compared with two commercial OCT systems. The human eye ciliary body was better visualized with the dynamic-focusing SS-OCT system than using the commercial 840 and 1310 nm OCT systems. The sulcus-to-sulcus distance was measured, and the result agreed with that acquired with ultrasound biomicroscopy.

Extended axial imaging range, widefield swept source optical coherence tomography angiography

We developed a high-speed, swept source OCT system for widefield OCT angiography (OCTA) imaging. The system has an extended axial imaging range of 6.6 mm. An electrical lens is used for fast, automatic focusing. The recently developed split-spectrum amplitude and phase-gradient angiography allow high-resolution OCTA imaging with only two B-scan repetitions. An improved post-processing algorithm effectively removed trigger jitter artifacts and reduced noise in the flow signal. We demonstrated high contrast 3 mm×3 mm OCTA image with 400×400 pixels acquired in 3 seconds and high-definition 8 mm×6 mm and 12 mm×6 mm OCTA images with 850×400 pixels obtained in 4 seconds. A widefield 8 mm×11 mm OCTA image is produced by montaging two 8 mm×6 mm scans. An ultra-widefield (with a maximum of 22 mm along both vertical and horizontal directions) capillary-resolution OCTA image is obtained by montaging six 12 mm×6 mm scans.