Yiheng Lim

Visualization of phase retardation of deep posterior eye by polarization-sensitive swept-source optical coherence tomography with 1-µm probe

Polarization-sensitive optical coherence tomography (PS-OCT) can measure cross-sectional and volumetric images of birefringence in fibrous tissues that provides additional contrast to the intensity images. In this study, we develop polarization-sensitive swept-source OCT (PS-SS-OCT) at 1 microm for deep penetration of the sclera and lamina cribrosa in the posterior part of human eyes. A calibration method for polarization mode dispersion of a circulator, which is employed to conserve the optical power of the interferometer and achieve system sensitivity sufficient for retinal imaging is demonstrated. The A-scan rate, the axial resolution, and the sensitivity of the PS-SS-OCT are 28,000 Hz, 11.0 microm, 94.2 dB, respectively. The posterior part of the eyes of a healthy male subject are measured in vivo. Phase-retardation images show birefringence of deep sclera and lamina cribrosa and enhance the contrast which is not visible in the intensity images. In addition, unlike conventional OCT, our PS-SS-OCT showed polarization-insensitive intensity images, in which an artifact created by the birefringence of sclera has been successfully eliminated.

Birefringence measurement of cornea and anterior segment by office-based polarization-sensitive optical coherence tomography

We present a case series of cornea and anterior segment disorders investigated by an office-based polarization-sensitive optical coherence tomography (PS-OCT). Blebs of glaucoma patients treated by trabeculectomy, and corneas of keratoconus and keratoplasty patients were measured by PS-OCT. Birefringence formations in trabeculectomy bleb were measured in 1 control eye and 3 eyes of trabeculectomy model rabbits. Polarization insensitive scattering OCT and the depth-resolved birefringence were measured simultaneously by PS-OCT. Abnormal birefringence was observed in keratoconus cases with advanced thinning and with a rupture of Descemet’s membrane. The graft-host interface of the keratoplasty case showed abnormal birefringence. The appearance of abnormal birefringence in the cornea was likely to be an indication of cross-linking of collagen fibrils. The measurement of rabbit showed abnormal birefringence in the scarring eyes. Wide regions of strong birefringence were observed in the eyes of trabeculectomy patients who had high intraocular pressure. Visualization of scarring in bleb by PS-OCT may be useful for the planning of secondary surgery. PS-OCT showed promising for the study and diagnosis diseases related to abnormal fibrous tissues of the cornea and anterior eye segment.

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.

Passive component based multifunctional Jones matrix swept source optical coherence tomography for Doppler and polarization imaging

We present a fiber based multifunctional Jones matrix swept source optical coherence tomography (SS-OCT) system for Doppler and polarization imaging. Jones matrix measurement without using active components such as electro-optic modulators is realized by incident polarization multiplexing based on independent delay of two orthogonal polarization states and polarization diversity detection. In addition to polarization sensitivity, this system measures Doppler flow without extra hardware for phase stabilized SS-OCT detection. An eighth-wave plate was measured to demonstrate the polarization detection accuracy. The optic nerve head of a retina was measured in vivo. Detailed vasculature and birefringent structures were investigated simultaneously.

Full-range polarization-sensitive swept-source optical coherence tomography by simultaneous transversal and spectral modulation

Polarization-sensitive swept-source optical coherence tomography (PS-SS-OCT) is used to measure three-dimensional phase-retardation images of birefringent biological tissue in vivo. PS-SS-OCT with continuous source polarization modulation is used to multiplex the incident states of polarization in the signal frequency of each A-scan. Although it offers the advantage of measurement speed that is as high as that of standard SS-OCT, its disadvantage is low axial measurement range. To overcome this drawback, we employed the B-M-mode scan (BM-scan) method, which removes complex conjugate ambiguity by applying phase modulation along the transversal scanning direction. Since polarization modulation and BM-scan are applied in different scanning directions, these methods can be combined to make the optimum use of both full range and polarization-sensitive imaging. Phase fluctuations that cause measurement failure were numerically canceled before demodulating the B-scan oriented modulation. After removing complex conjugate artifacts, the axial measurement range was 5.35 mm, and the signal-to-conjugate ratio was 40.5 dB. We demonstrated retinal imaging using the PS-SS-OCT system with a frequency-swept laser at a center wavelength of 1064 nm and an axial resolution of 11.4 microm in tissue. Full-range polarization-sensitive retinal images showed characteristic birefringence of fibrous tissues such as retinal nerve fiber, sclera, and lamina cribrosa.

In vivo evaluation of human skin anisotropy by polarization-sensitive optical coherence tomography

Abstract We performed an in vivo three-dimensional analysis of anisotropic changes in the dermal birefringence of mechanically deformed human skin using polarization-sensitive optical coherence tomography (PS-OCT). The papillary-dermal birefringence of the forehead increased significantly when the skin was shrunk parallel to the body axis, and decreased significantly when the skin was shrunk perpendicular to the body axis. En-face images of the papillary-dermal birefringence revealed variations among individual subjects, and that both shrinking parallel to and stretching in perpendicular to the body axis promoted the formation of macro rope-like birefringent domains. We found that PS-OCT is useful for understanding anisotropic properties of collagen structure in the skin.

Keratoconus Diagnosis Using Anterior Segment Polarization-Sensitive Optical Coherence Tomography

PURPOSE To investigate the tissue properties of keratoconic and normal corneas in vivo by using polarization-sensitive optical coherence tomography (PS-OCT), and to evaluate early keratoconus by the area under the receiver operating characteristic curve (AUROC) and Mahalanobis distance analysis. METHODS Thirty-one eyes of 20 patients with keratoconus, 7 eyes of 7 patients with keratoconus suspect, and 25 eyes of 25 normal subjects were investigated by PS-OCT and corneal and anterior segment (CAS)-OCT. Average of en face phase retardation of the posterior surface of the cornea, curvature, videokeratographic parameters, regular and irregular astigmatism, pachymetry map, and elevation were measured. The AUROC of each parameter was calculated to evaluate the diagnostic power to detect keratoconus and keratoconus suspect. RESULTS While in normal controls, the center of the en face phase retardation map showed low and homogeneous birefringence, in keratoconic corneas the birefringence increased with disease severity. Some keratoconus suspects had apparent high birefringence values without displaying morphologic signs of keratoconus in the anterior surface. The phase retardation values for normal, keratoconus suspect, and keratoconus subjects were, respectively, 0.20 ± 0.06, 0.35 ± 0.06, and 0.50 ± 0.14 radians in 3 mm diameter and 0.29 ± 0.22, 0.33 ± 0.13, and 0.74 ± 0.45 radians in 6 mm diameter. Outer morphological parameters such as curvature, videokeratographic parameters, regular and irregular astigmatism, and elevation showed high AUROCs for discriminating keratoconus from normal controls. On the other hand, using Mahalanobis distance, the AUROC of phase retardation, which represents microstructural properties of tissue, showed high value (0.989-1.000) for discriminating between keratoconus suspects and normal controls. CONCLUSIONS Average of en face phase retardation of the posterior surface of the cornea was increased in keratoconus patients due to changes in the lamellar structure of collagen fibers. Phase retardation was sensitive with regard to discriminating keratoconus suspect and might be useful for detecting very early or even subclinical keratoconus.

Monte-Carlo-based phase retardation estimator for polarization sensitive optical coherence tomography

A Monte-Carlo-based phase retardation estimator is developed to correct the systematic error in phase retardation measurement by polarization sensitive optical coherence tomography (PS-OCT). Recent research has revealed that the phase retardation measured by PS-OCT has a distribution that is neither symmetric nor centered at the true value. Hence, a standard mean estimator gives us erroneous estimations of phase retardation, and it degrades the performance of PS-OCT for quantitative assessment. In this paper, the noise property in phase retardation is investigated in detail by Monte-Carlo simulation and experiments. A distribution transform function is designed to eliminate the systematic error by using the result of the Monte-Carlo simulation. This distribution transformation is followed by a mean estimator. This process provides a significantly better estimation of phase retardation than a standard mean estimator. This method is validated both by numerical simulations and experiments. The application of this method to in vitro and in vivo biological samples is also demonstrated.

Optical Rheology of Porcine Sclera by Birefringence Imaging

Purpose To investigate a relationship between birefringence and elasticity of porcine sclera ex vivo using polarization-sensitive optical coherence tomography (PS-OCT). Methods Elastic parameters and birefringence of 19 porcine eyes were measured. Four pieces of scleral strips which were parallel to the limbus, with a width of 4 mm, were dissected from the optic nerve head to the temporal side of each porcine eye. Birefringence of the sclera was measured with a prototype PS-OCT. The strain and force were measured with a uniaxial material tester as the sample was stretched with a speed of 1.8 mm/min after preconditioning. A derivative of the exponentially-fitted stress-strain curve at 0% strain was extracted as the tangent modulus. Power of exponential stress-strain function was also extracted from the fitting. To consider a net stiffness of sclera, structural stiffness was calculated as a product of tangent modulus and thickness. Correlations between birefringence and these elastic parameters were examined. Results Statistically significant correlations between birefringence and all of the elastic parameters were found at 2 central positions. Structural stiffness and power of exponential stress-strain function were correlated with birefringence at the position near the optic nerve head. No correlation was found at the position near the equator. Conclusions The evidence of correlations between birefringence and elasticity of sclera tested uniaxially was shown for the first time. This work may become a basis for in vivo measurement of scleral biomechanics using PS-OCT.

Multimodal analysis of pearls and pearl treatments by using optical coherence tomography and fluorescence spectroscopy

We present an integrated optical system that consists of optical coherence tomography (OCT) and laser-induced fluorescence (LIF) spectroscopy for multimodal analysis of pearls and pearl treatments. The OCT source and the LIF excitation beams were aligned together to illuminate the same spot of a pearl fixed on the sample stage that was under rotation. As a result, both OCT images and LIF spectra of the pearls were detected at the same time and also at the same place. For OCT, a 1310 nm-centered swept laser source was used. For LIF, a 405 nm laser diode was used and a lensed multimode fiber was utilized as a fluorescence probe. The tomographic investigation on the internal structure of a pearl allowed us to evaluate and categorize the pearl nondestructively as was previously reported. In addition, the measurements of fluorescence spectrum and its decaying rate helped to determine the species of mother oyster. The proposed multimodal analysis made it possible to classify the pearls and also to disclose the treatments made on the pearls.