Xiaojun Yu

Dual spectrometer system with spectral compounding for 1-μm optical coherence tomography in vivo.

1 μm axial resolution spectral domain optical coherence tomography (OCT) is demonstrated for in vivo cellular resolution imaging. Output of two superluminescent diode sources is combined to provide near infrared illumination from 755 to 1105 nm. The spectral interference is detected using two spectrometers based on a Si camera and an InGaAs camera, respectively. Spectra from the two spectrometers are combined to achieve an axial resolution of 1.27 μm in air. Imaging was conducted on zebra fish larvae to visualize cellular details.

High-resolution extended source optical coherence tomography

High resolution optical coherence tomography (OCT) is capable of providing detailed tissue microstructures that are critical for disease diagnosis, yet its sensitivity is usually degraded since the system key components are typically not working at their respective center wavelengths. We developed a novel imaging system that achieves enhanced sensitivity without axial resolution degradation by the use of a spectrally encoded extended source (SEES) technique; it allows larger sample power without exceeding the maximum permissible exposure (MPE). In this study, we demonstrate a high-resolution extended source (HRES) OCT system, which is capable of providing a transverse resolution of 4.4 µm and an axial resolution of 2.1 µm in air with the SEES technique. We first theoretically show a sensitivity advantage of 6-dB of the HRES-OCT over that of its point source counterpart using numerical simulations, and then experimentally validate the applicability of the SEES technique to high-resolution OCT (HR-OCT) by comparing the HRES-OCT with an equivalent point-source system. In the HRES-OCT system, a dispersive prism was placed in the infinity space of the sample arm optics to spectrally extend the visual angle (angular subtense) of the light source to 10.3 mrad. This extended source allowed ~4 times larger MPE than its point source counterpart, which results in an enhancement of ~6 dB in sensitivity. Specifically, to solve the unbalanced dispersion between the sample and the reference arm optics, we proposed easy and efficient methods for system calibration and dispersion correction, respectively. With a maximum scanning speed reaching up to 60K A-lines/s, we further conducted imaging experiments with HRES-OCT using the human fingertip in vivo and the swine eye tissues ex vivo. Results demonstrate that the HRES-OCT is able to achieve significantly larger penetration depth than its conventional point source OCT counterpart.

Depth extension and sidelobe suppression in optical coherence tomography using pupil filters

We demonstrate a new focus engineering scheme to achieve both extended depth of focus (DOF) and sidelobe suppression in spectral-domain optical coherence tomography (SD-OCT) system. Each of the illumination pupil function and the detection pupil function is modulated using an annular pupil filter implemented by center obscuration. The two pupil filters are arranged in a dark-field configuration such that the first sidelobe of the illumination point-spread function (PSF) matches the first minimum of the detection PSF in the lateral focal plane. We tested the feasibility of the proposed scheme numerically, and then constructed a dark-field OCT (DF-OCT) system to further verify its effectiveness experimentally. Simulation results show that a DOF gain of 4.2 can be achieved compared with a full aperture OCT (FA-OCT) system, with a suppression ratio of 2.9 dB for the first sidelobe compared with an annular-aperture bright-field OCT (BF-OCT) system. Experimental results show that the constructed DF-OCT extends the DOF by three-fold compared with the constructed FA-OCT, and suppresses the first sidelobe by 3.1 dB compared with the BF-OCT. The penalty for the extended DOF is an ~11.6 dB drop in sensitivity compared with the FA-OCT system.

Spectral estimation optical coherence tomography for axial super-resolution.

The depth reflectivity profile of Fourier domain optical coherence tomography (FD-OCT) is estimated from the inverse Fourier transform of the spectral interference signals (interferograms). As a result, the axial resolution is fundamentally limited by the coherence length of the light source. We demonstrate that using the autoregressive spectral estimation technique instead of the inverse Fourier transform, to analyze the spectral interferograms can improve the axial resolution. We name this method spectral estimation OCT (SE-OCT). SE-OCT breaks the coherence length limitation and improves the axial resolution by a factor of up to 4.7 compared with FD-OCT. Furthermore, SE-OCT provides complete sidelobe suppression in the depth point-spread function, further improving the image quality. We demonstrate that these technical advances enables clear identification of corneal endothelium anatomical details ex vivo that cannot be identified using the corresponding FD-OCT. Given that SE-OCT can be implemented in the FD-OCT devices without any hardware changes, the new capabilities provided by SE-OCT are likely to offer immediate improvements to the diagnosis and management of diseases based on OCT imaging.

Spectrally encoded extended source optical coherence tomography.

We have developed an extended source optical coherence tomography (SEES-OCT) technique in an attempt to improve signal strength for ophthalmic imaging. A line illumination with a visual angle of 7.9xa0mrad is produced by introducing a dispersive element in the infinity space of the sample arm. The maximum permissible exposure (MPE) of such an extended source is 3.1 times larger than that of a standard point source OCT, which corresponds to sensitivity improvement of 5xa0dB. The advantage of SEES-OCT in providing superior penetration depth over a point source system is demonstrated using swine eye tissues ex vivo.

Toward High-Speed Imaging of Cellular Structures in Rat Colon Using Micro-optical Coherence Tomography

The mucosal microanatomy of the large intestine is characterized by the presence of crypts of Lieberkühn, which is associated predominantly with goblet cells. Such cellular-level intestinal microstructures undergo morphological changes during the progression of bowel diseases, such as colon cancer or ulcerative colitis. As an indicator of gastric cancers, intestinal metaplasia in the large intestine is characterized by the appearance of goblet cells in gastric epithelium, and therefore, visualization of intestinal microstructure changes in cross-sectional view, particularly in vivo, in a high-speed fashion would assist early disease diagnosis and its treatment. In this paper, we investigated the capability of micro-optical coherence tomography (μOCT) for high-speed cellular-level crypt and goblet cell structures imaging ex vivo and in vivo . The adopted μOCT system achieved a resolution of 2.0 μm in both the lateral and axial directions in air. Ex vivo and video-rate in vivo images acquired in 3-D at respective imaging rates of 20 and 60 frames/s are presented and compared with the histology images. Imaging results show that the detailed microstructures, such as the crypt lumen and the goblet cells, could be clearly identified and are also comparable with those in histology images. Such comparisons also indicate that high-resolution μOCT could be a powerful tool to perform “optical biopsy” in colorectal tissue. This is the first work, to the best of our knowledge, on cellular-level structure imaging in intestinal mucosa using spectral-domain OCT.

Spectral-domain optical coherence tomography with dual-balanced detection for auto-correlation artifacts reduction

We developed a spectral domain optical coherence tomography (SD-OCT) to reduce auto-correlation artifacts (AC) using dual-balanced detection (DBD). AC were composed of the interference signals between different sample tissue depths, and shown up as artifacts in OCT images. This system employed a free-space Michelson interferometer, at the refraction plane of whose beam splitter, the light reflected experienced a π/2 phase shift with respect to the light transmitted. Then two phase-opposed interferometric spectra sharing the same spectrometer optics were obtained simultaneously using two lines of a three-line CCD. This new design was of lower cost compared to the dual spectrometer design reported previously. DBD enabled this SD-OCT to achieve two-fold increase in the interested signal amplitude inherently, and obtain a SNR increase of ~2.9 dB experimentally. To demonstrate the feasibility and performance of this SD-OCT system with DBD, we conducted an imaging experiment using a glass plate to obtain the optimal spectral matching between dual-balanced spectrometer channels. As a result, this SD-OCT achieved AC reduction up to about 9 dB and direct current (DC) term suppression up to about 30 dB by cancelling the identical components between dual-balanced spectrometer channels. The efficacy of AC reduction and DC suppression was validated by imaging the polymer coating of a drug-eluting stent and fresh swine corneal tissue ex vivo. The quality of DBD optimized images was significantly improved with regard to the single-channel images.

Contrast Enhanced Subsurface Fingerprint Detection Using High-Speed Optical Coherence Tomography

Spectral-domain optical coherence tomography (SD-OCT) has been demonstrated to be a viable tool in forensic science for fingerprint detection, yet it still suffers from certain practical issues, e.g., the limited scanning speed and low image contrast. In this letter, we report a high-speed SD-OCT together with an image contrast enhancement mechanism for reliable subsurface fingerprint detection. The constructed SD-OCT system achieves a scanning rate up to 60k A-lines/s, and thus, both 3D volumetric images, reaching up to 20 mm × 20 mm × 1.2 mm, and en face internal fingerprint furrow pattern images could be obtained. Based upon the analyses of the papillary layer anatomical structures, the contrast enhancement technique not only suppresses image artifacts, but also is effective in detecting fingerprint spoofing. Experiments on healthy subjects have also been conducted to verify the system imaging capability and the effectiveness of the contrast-enhancement technique.

Single-camera full-range high-resolution spectral domain optical coherence tomography

We developed spectral domain optical coherence tomography using a dual-channel spectrometer for complex conjugate artifacts (CCA) suppression. We used a three-line charge coupled device to simultaneously detect two interferometric spectra with 2π/3 phase difference. The complex interferometric signal was reconstructed by trigonometric manipulation of two real interferometric spectra, and then full-range images were obtained by use of inverse Fourier transform. Artifacts at direct current (DC) and the ghost remnant of the CCA are common issues with the previously reported two-spectrometer method because the slight mismatching between two spectral detection channels had strong negative effects on CCA suppression and appeared to be the limiting factor on system performance. This novel dual-channel spectrometer uses the same spectrometer optics for the two spectral detection channels and, therefore, achieves better matching between two spectral detection channels and consequently better performance in CCA suppression as compared with the dual spectrometer solution. Full-range imaging with CCA suppression up to ∼25u2009u2009dB was demonstrated when imaging an attenuated reflector. The efficacy of both CCA and DC suppressions also was validated by imaging the anterior segment of a rat eye ex vivo. The quality of CCA-suppressed images was significantly improved with regard to those obtained with the dual-spectrometer design.

Modeling of Mechanical Stress Exerted by Cholesterol Crystallization on Atherosclerotic Plaques

Plaque rupture is the critical cause of cardiovascular thrombosis, but the detailed mechanisms are not fully understood. Recent studies have found abundant cholesterol crystals in ruptured plaques, and it has been proposed that the rapid expansion of cholesterol crystals in a limited space during crystallization may contribute to plaque rupture. To evaluate the effect of cholesterol crystal growth on atherosclerotic plaques, we modeled the expansion of cholesterol crystals during the crystallization process in the necrotic core and estimated the stress on the thin cap with different arrangements of cholesterol crystals. We developed a two-dimensional finite element method model of atherosclerotic plaques containing expanding cholesterol crystals and investigated the effect of the magnitude and distribution of crystallization on the peak circumferential stress born by the cap. Using micro-optical coherence tomography (μOCT), we extracted the cross-sectional geometric information of cholesterol crystals in human atherosclerotic aorta tissue ex vivo and applied the information to the model. The results demonstrate that (1) the peak circumference stress is proportionally dependent on the cholesterol crystal growth; (2) cholesterol crystals at the cap shoulder impose the highest peak circumference stress; and (3) spatial distributions of cholesterol crystals have a significant impact on the peak circumference stress: evenly distributed cholesterol crystals exert less peak circumferential stress on the cap than concentrated crystals.