Machine-learning based segmentation of the optic nerve head using multi-contrast Jones matrix optical coherence tomography with semi-automatic training dataset generation.

A pixel-by-pixel tissue classification framework using multiple contrasts obtained by Jones matrix optical coherence tomography (JM-OCT) is demonstrated. The JM-OCT is an extension of OCT that provides OCT, OCT angiography, birefringence tomography, degree-of-polarization uniformity tomography, and attenuation coefficient tomography, simultaneously. The classification framework consists of feature engineering, k-means clustering that generates a training dataset, training of a tissue classifier using the generated training dataset, and tissue classification by the trained classifier. The feature engineering process generates synthetic features from the primary optical contrasts obtained by JM-OCT. The tissue classification is performed in the feature space of the engineered features. We applied this framework to the in vivo analysis of optic nerve heads of posterior eyes. This classified each JM-OCT pixel into prelamina, lamina cribrosa (lamina beam), and retrolamina tissues. The lamina beam segmentation results were further utilized for birefringence and attenuation coefficient analysis of lamina beam.

Eye-motion-corrected optical coherence tomography angiography using Lissajous scanning.

To correct eye motion artifacts in en face optical coherence tomography angiography (OCT-A) images, a Lissajous scanning method with subsequent software-based motion correction is proposed. The standard Lissajous scanning pattern is modified to be compatible with OCT-A and a corresponding motion correction algorithm is designed. The effectiveness of our method was demonstrated by comparing en face OCT-A images with and without motion correction. The method was further validated by comparing motion-corrected images with scanning laser ophthalmoscopy images, and the repeatability of the method was evaluated using a checkerboard image. A motion-corrected en face OCT-A image from a blinking case is presented to demonstrate the ability of the method to deal with eye blinking. Results show that the method can produce accurate motion-free en face OCT-A images of the posterior segment of the eye in vivo.

Generation and optimization of superpixels as image processing kernels for Jones matrix optical coherence tomography.

Jones matrix-based polarization sensitive optical coherence tomography (JM-OCT) simultaneously measures optical intensity, birefringence, degree of polarization uniformity, and OCT angiography. The statistics of the optical features in a local region, such as the local mean of the OCT intensity, are frequently used for image processing and the quantitative analysis of JM-OCT. Conventionally, local statistics have been computed with fixed-size rectangular kernels. However, this results in a trade-off between image sharpness and statistical accuracy. We introduce a superpixel method to JM-OCT for generating the flexible kernels of local statistics. A superpixel is a cluster of image pixels that is formed by the pixels' spatial and signal value proximities. An algorithm for superpixel generation specialized for JM-OCT and its optimization methods are presented in this paper. The spatial proximity is in two-dimensional cross-sectional space and the signal values are the four optical features. Hence, the superpixel method is a six-dimensional clustering technique for JM-OCT pixels. The performance of the JM-OCT superpixels and its optimization methods are evaluated in detail using JM-OCT datasets of posterior eyes. The superpixels were found to well preserve tissue structures, such as layer structures, sclera, vessels, and retinal pigment epithelium. And hence, they are more suitable for local statistics kernels than conventional uniform rectangular kernels.

Noise-bias and polarization-artifact corrected optical coherence tomography by maximum a-posteriori intensity estimation.

We propose using maximum a-posteriori (MAP) estimation to improve the image signal-to-noise ratio (SNR) in polarization diversity (PD) optical coherence tomography. PD-detection removes polarization artifacts, which are common when imaging highly birefringent tissue or when using a flexible fiber catheter. However, dividing the probe power to two polarization detection channels inevitably reduces the SNR. Applying MAP estimation to PD-OCT allows for the removal of polarization artifacts while maintaining and improving image SNR. The effectiveness of the MAP-PD method is evaluated by comparing it with MAP-non-PD, intensity averaged PD, and intensity averaged non-PD methods. Evaluation was conducted in vivo with human eyes. The MAP-PD method is found to be optimal, demonstrating high SNR and artifact suppression, especially for highly birefringent tissue, such as the peripapillary sclera. The MAP-PD based attenuation coefficient image also shows better differentiation of attenuation levels than non-MAP attenuation images.

Three-dimensional multi-contrast imaging of in vivo human skin by Jones matrix optical coherence tomography.

A custom made dermatological Jones matrix optical coherence tomography (JM-OCT) is presented. It uses a passive-polarization-delay component based swept-source JM-OCT configuration, but is specially designed for in vivo human skin measurement. The center wavelength of its probe beam is 1310 nm and the A-line rate is 49.6 kHz. The JM-OCT is capable of simultaneously providing birefringence (local retardation) tomography, degree-of-polarization-uniformity tomography, complex-correlation-based optical coherence angiography, and conventional scattering OCT. To evaluate the performance of this JM-OCT, we measured in vivo human skin at several locations. Using the four kinds of OCT contrasts, the morphological characteristics and optical properties of different skin types were visualized.

Three-dimensional eye motion correction by Lissajous scan optical coherence tomography.

A three-dimensional optical coherence tomography imaging method based on Lissajous scanning is presented. This method was designed to correct eye motion in OCT images. A Lissajous scanning pattern, which has a trajectory that frequently overlaps with itself, is adopted as the OCT scanning protocol to obtain measurement data. Eye motion artifacts are then corrected automatically by software. By comparing the images without and with motion correction, we show the effectiveness of our method. We performed an experiment and compared the results obtained by our method with the ground truths to verify its validity. The experimental results showed that our method effectively corrects eye motion artifacts. Furthermore, the sufficient repeatability of our method was confirmed.

Evaluation of intraretinal migration of retinal pigment epithelial cells in age-related macular degeneration using polarimetric imaging.

The purpose of the present study was to evaluate the intraretinal migration of the retinal pigment epithelium (RPE) cells in age-related macular degeneration (AMD) using polarimetry. We evaluated 155 eyes at various AMD stages. Depolarized light images were computed using a polarization-sensitive scanning laser ophthalmoscope (PS-SLO), and the degree of polarization uniformity was calculated using polarization-sensitive optical coherence tomography (OCT). Each polarimetry image was compared with the corresponding autofluorescence (AF) images at 488 nm (SW-AF) and at 787 nm (NIR-AF). Intraretinal RPE migration was defined by the presence of depolarization at intraretinal hyperreflective foci on PS-SLO and PS-OCT images, and by the presence of hyper-AF on both NIR-AF and SW-AF images. RPE migration was detected in 52 of 155 eyes (33.5%) and was observed in drusenoid pigment epithelial detachment (PED) and serous PED with significantly higher frequencies than in other groups (P = 0.015). The volume of the migrated RPE cluster in serous PED was significantly correlated with the volume of the PED (R2 = 0.26; P = 0.011). Overall, our results showed that intraretinal RPE migrations occurred in various AMD stages, and that they occurred more commonly in eyes with serous and drusenoid PED.

Noise stochastic corrected maximum a posteriori estimator for birefringence imaging using polarization-sensitive optical coherence tomography.

This paper presents a noise-stochastic corrected maximum a posteriori estimator for birefringence imaging using Jones matrix optical coherence tomography. The estimator described in this paper is based on the relationship between probability distribution functions of the measured birefringence and the effective signal to noise ratio (ESNR) as well as the true birefringence and the true ESNR. The Monte Carlo method is used to numerically describe this relationship and adaptive 2D kernel density estimation provides the likelihood for a posteriori estimation of the true birefringence. Improved estimation is shown for the new estimator with stochastic model of ESNR in comparison to the old estimator, both based on the Jones matrix noise model. A comparison with the mean estimator is also done. Numerical simulation validates the superiority of the new estimator. The superior performance of the new estimator was also shown by in vivo measurement of optic nerve head.

Noise-immune complex correlation for optical coherence angiography based on standard and Jones matrix optical coherence tomography.

This paper describes a complex correlation mapping algorithm for optical coherence angiography (cmOCA). The proposed algorithm avoids the signal-to-noise ratio dependence and exhibits low noise in vasculature imaging. The complex correlation coefficient of the signals, rather than that of the measured data are estimated, and two-step averaging is introduced. Algorithms of motion artifact removal based on non perfusing tissue detection using correlation are developed. The algorithms are implemented with Jones-matrix OCT. Simultaneous imaging of pigmented tissue and vasculature is also achieved using degree of polarization uniformity imaging with cmOCA. An application of cmOCA to in vivo posterior human eyes is presented to demonstrate that high-contrast images of patients' eyes can be obtained.

Birefringence imaging of posterior eye by multi-functional Jones matrix optical coherence tomography.

A clinical grade prototype of posterior multifunctional Jones matrix optical coherence tomography (JM-OCT) is presented. This JM-OCT visualized depth-localized birefringence in addition to conventional cumulative phase retardation imaging through local Jones matrix analysis. In addition, it simultaneously provides a sensitivity enhanced scattering OCT, a quantitative polarization uniformity contrast, and OCT-based angiography. The probe beam is at 1-µm wavelength band. The measurement speed and the depth-resolution were 100,000 A-lines/s, and 6.6 µm in tissue, respectively. Normal and pathologic eyes are examined and several clinical features are revealed, which includes high birefringence in the choroid and lamina cribrosa, and birefringent layered structure of the sclera. The theoretical details of the depth-localized birefringence imaging and conventional phase retardation imaging are formulated. This formulation indicates that the birefringence imaging correctly measures a depth-localized single-trip phase retardation of a tissue, while the conventional phase retardation can provide correct single-trip phase retardation only for some specific types of samples.

Noninvasive vascular imaging of ruptured retinal arterial macroaneurysms by Doppler optical coherence tomography.

BACKGROUND: To describe Doppler optical coherence tomography (OCT) imaging of ruptured retinal arterial macroaneurysms (RAMs). METHODS: Four eyes of four patients with ruptured RAMs were prospectively studied. Vascular imaging was obtained using swept-source Doppler OCT, and compared with indocyanine green angiography images. RESULTS: En face projection of Doppler OCT images clearly showed RAMs at the corresponding locations of lesions in the indocyanine green angiography images. In Doppler OCT images, RAMs were located in the inner retina in three eyes and in the medium layer of the retina in one eye. In one eye, detection of RAMs by standard OCT was difficult because of the presence of inner retinal hemorrhage. In one eye, disappearance of blood flow after direct laser photocoagulation could be confirmed by Doppler OCT images. CONCLUSIONS: Doppler OCT imaging may potentially function as a noninvasive complementary procedure with indocyanine green angiography.

In-plane and out-of-plane tissue micro-displacement measurement by correlation coefficients of optical coherence tomography.

We propose a method to measure the in-plane and out-of-plane displacements of tissue using the correlation coefficients of optical coherence tomography (OCT) signals. The displacements are determined by the local correlation coefficients between digitally shifted reference OCT images and a target image. The method achieves sub-micron displacement measurement with an accuracy better than 0.32 µm and repeatability better than 0.36 µm. The feasibility of the method was examined by measuring the displacement field of a laser irradiated porcine retina. This method successfully visualized the dynamic change of the displacement field during laser irradiation.

Noninvasive vascular imaging of polypoidal choroidal vasculopathy by Doppler optical coherence tomography.

PURPOSE: To noninvasively investigate the vascular architecture of polypoidal lesions in polypoidal choroidal vasculopathy (PCV) using Doppler optical coherence tomography (OCT), and to evaluate the clinical usefulness of Doppler OCT for the assessment of therapeutic effects in PCV. METHODS: Fifteen eyes of 15 patients with treatment-naïve PCV were prospectively studied. Vascular imaging was obtained using 1060-nm swept-source Doppler OCT, and compared with indocyanine green angiography (ICGA) images. The therapeutic effect of three consecutive intravitreal aflibercept injections was evaluated with ICGA and Doppler OCT. RESULTS: In Doppler OCT images, polypoidal lesions were clearly detected at the corresponding locations of lesions in the ICGA images. By being insensitive to dye leakage, Doppler OCT identified the complicated vascular structure in the polypoidal lesions. The identified mean area of the polypoidal lesions in the Doppler OCT images (0.04 mm(2)) was significantly smaller than that of the ICGA images (0.13 mm(2)). Polypoidal lesions were located in the retinal pigment epithelial detachment in 13 eyes, in the choroid in one eye, and in both the retinal pigment epithelial detachment and choroid in one eye. After intravitreal aflibercept treatment, areas of polypoidal lesions in the ICGA images were decreased in 14 of 15 eyes. This therapeutic effect was clearly confirmed in the Doppler OCT images. CONCLUSIONS: Doppler OCT imaging clearly detected fine vascular structures at the polypoidal lesions in PCV. Doppler OCT might be useful for the diagnosis and evaluation of therapeutic effects in PCV.

Two-dimensional micro-displacement measurement for laser coagulation using optical coherence tomography.

To improve the reproducibility of photocoagulation, the ability to quantitatively monitor the thermal change of laser-irradiated retinal tissue is required. Recently, optical coherence tomography has enabled non-invasive and non-contact monitoring of the tissue structural changes during laser irradiation. To further improve the capability of this technique, a method is proposed to measure tissue displacement by simultaneously using Doppler phase shifts and correlation coefficients. The theoretical approach for this method is described, and its performance is experimentally confirmed and evaluated. Finally, lateral and axial displacements in the laser-irradiated retinal tissues of an enucleated porcine eye are observed. The proposed method is found to be useful for further understanding the direct thermal response of laser-irradiated retinal tissue.

Optically buffered Jones-matrix-based multifunctional optical coherence tomography with polarization mode dispersion correction.

Polarization mode dispersion (PMD) degrades the performance of Jones-matrix-based polarization-sensitive multifunctional optical coherence tomography (JM-OCT). The problem is specially acute for optically buffered JM-OCT, because the long fiber in the optical buffering module induces a large amount of PMD. This paper aims at presenting a method to correct the effect of PMD in JM-OCT. We first mathematically model the PMD in JM-OCT and then derive a method to correct the PMD. This method is a combination of simple hardware modification and subsequent software correction. The hardware modification is introduction of two polarizers which transform the PMD into global complex modulation of Jones matrix. Subsequently, the software correction demodulates the global modulation. The method is validated with an experimentally obtained point spread function with a mirror sample, as well as by in vivo measurement of a human retina.

Three-dimensional vascular imaging of proliferative diabetic retinopathy by Doppler optical coherence tomography.

PURPOSE: To evaluate the 3-dimensional architecture of neovascularization in proliferative diabetic retinopathy using Doppler optical coherence tomography (OCT). DESIGN: Prospective, nonrandomized clinical trial. METHODS: Seventeen eyes of 14 patients with proliferative diabetic retinopathy were prospectively studied. Prototype Doppler OCT was used to evaluate the 3-dimensional vascular architecture at vitreoretinal adhesions. RESULTS: Proliferative membranes were detected in all eyes with proliferative diabetic retinopathy by standard OCT images. Doppler OCT images detected blood flow by neovascularization of the disc in 12 eyes and neovascularization elsewhere in 11 eyes. Doppler OCT images showed the 3-dimensional extent of new vessels at various stages of neovascularization, and the extent of new vessels could be clearly confirmed at vitreoretinal adhesions. CONCLUSIONS: Doppler OCT is useful for the detection and evaluation of the 3-dimensional vascular structure of neovascularization, and can assist in the noninvasive assessment of proliferative diabetic retinopathy.

Degree of polarization uniformity with high noise immunity using polarization-sensitive optical coherence tomography.

A new metric representing polarization uniformity is presented. Noise corrected degree of polarization uniformity (DOPU) is computed from polarization-sensitive optical coherence tomography (OCT), and selectively visualizes tissue with the multiple scattering, such as highly pigmented tissues. The new metric is designed to be minimally sensitive to systematic additive noise. The performance of this new metric is analyzed by numerical simulation and in vivo human retinal imaging, using Jones matrix OCT. The new metric exhibited only a small dependency on the signal-to-noise ratio. Selective in vivo visualization of pigmented tissues in the human retina is demonstrated, with cross sectional and en-face images.

Simultaneous investigation of vascular and retinal pigment epithelial pathologies of exudative macular diseases by multifunctional optical coherence tomography.

PURPOSE: To investigate exudative macular disease, multifunctional optical coherence tomography (MF-OCT) using a 1-µm probe band was developed. The clinical utility of MF-OCT was examined in a descriptive case series. METHODS: Ten eyes of nine subjects with exudative macular disease, including one eye with age-related macular degeneration (AMD), one eye with idiopathic neovascular maculopathy, and eight eyes with polypoidal choroidal vasculopathy (PCV), were investigated. Areas of 6 × 6 mm(2) around the pathologic region were scanned with 512 × 1024 depth scans in 6.6 seconds. Structural OCT, Doppler optical coherence angiography (OCA), and cumulative phase retardation images were obtained with a single measurement. Each MF-OCT image visualized the structure, vasculature, and birefringence. Degree of polarization uniformity values were also obtained for selective visualization of the retinal pigment epithelium (RPE). The MF-OCT images were compared with conventional ophthalmic images. RESULTS: Abnormal vasculatures were observed with Doppler OCA in all eyes, which presented high similarity to indocyanine green angiography in the midphase. The RPE and exudation in the pathologic regions were discriminated in one eye with AMD and five of eight eyes with PCV. Cumulative phase retardation visualized fibrosis scars in two of the PCV cases. CONCLUSIONS: Multifunctional OCT revealed depth-resolved abnormal vasculatures, the integrity of the RPE and choroid, discrimination of the RPE and exudation, and existence of fibrosis scars in exudative macular diseases. Interpretation of MF-OCT examination is well matched with conventional ophthalmic examination. These results suggest that MF-OCT can be used as a noninvasive ophthalmic examination tool prior to conventional examinations in clinical routines.

Biosynthetic consequences of multiple sequential post-transition-state bifurcations.

Selectivity in chemical reactions that form complex molecular architectures from simpler precursors is usually rationalized by comparing competing transition-state structures that lead to different possible products. Herein we describe a system for which a single transition-state structure leads to the formation of many isomeric products via pathways that feature multiple sequential bifurcations. The reaction network described connects the pimar-15-en-8-yl cation to miltiradiene, a tricyclic diterpene natural product, and isomers via cyclizations and/or rearrangements. The results suggest that the selectivity of the reaction is controlled by (post-transition-state) dynamic effects, that is, how the carbocation structure changes in response to the distribution of energy in its vibrational modes. The inherent dynamical effects revealed herein (characterized through quasiclassical direct dynamics calculations using density functional theory) have implications not only for the general principles of selectivity prediction in systems with complex potential energy surfaces, but also for the mechanisms of terpene synthase enzymes and their evolution. These findings redefine the challenges faced by nature in controlling the biosynthesis of complex natural products.

Advanced multi-contrast Jones matrix optical coherence tomography for Doppler and polarization sensitive imaging.

An advanced version of Jones matrix optical coherence tomography (JMT) is demonstrated for Doppler and polarization sensitive imaging of the posterior eye. JMT is capable of providing localized flow tomography by Doppler detection and investigating the birefringence property of tissue through a three-dimensional (3-D) Jones matrix measurement. Owing to an incident polarization multiplexing scheme based on passive optical components, this system is stable, safe in a clinical environment, and cost effective. Since the properties of this version of JMT provide intrinsic compensation for system imperfection, the system is easy to calibrate. Compared with the previous version of JMT, this advanced JMT achieves a sufficiently long depth measurement range for clinical cases of posterior eye disease. Furthermore, a fine spectral shift compensation method based on the cross-correlation of calibration signals was devised for stabilizing the phase of OCT, which enables a high sensitivity Doppler OCT measurement. In addition, a new theory of JMT which integrates the Jones matrix measurement, Doppler measurement, and scattering measurement is presented. This theory enables a sensitivity-enhanced scattering OCT and high-sensitivity Doppler OCT. These new features enable the application of this system to clinical cases. A healthy subject and a geographic atrophy patient were measured in vivo, and simultaneous imaging of choroidal vasculature and birefringence structures are demonstrated.