Yuemei Luo

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.

Enhancement and bias removal of optical coherence tomography images

Optical coherence tomography (OCT) has continually evolved and expanded as one of the most valuable routine tests in ophthalmology. However, noise (speckle) in the acquired images causes quality degradation of OCT images and makes it difficult to analyze the acquired images. In this paper, an iterative approach based on bilateral filtering is proposed for speckle reduction in multiframe OCT data. Gamma noise model is assumed for the observed OCT image. First, the adaptive version of the conventional bilateral filter is applied to enhance the multiframe OCT data and then the bias due to noise is reduced from each of the filtered frames. These unbiased filtered frames are then refined using an iterative approach. Finally, these refined frames are averaged to produce the denoised OCT image. Experimental results on phantom images and real OCT retinal images demonstrate the effectiveness of the proposed filter.

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.

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.

Depth of focus extension in optical coherence tomography via multiple aperture synthesis

In this paper, we report what we believe is a novel technique to overcome the depth-of-focus (DOF) limitation in optical coherence tomography (OCT). Using confocal optics on a sample arm, we scanned the illumination beam across the under-filled objective lens pupil plane by steering the beam at the pinhole using a microcylindrical lens. The detected interferometric signals from multiple distinctive apertures were digitally refocused, which is analogous to synthetic aperture radar (SAR). Using numerical simulations and imaging experiments, we verified that this technique can maintain a diffraction-limited transverse resolution along a DOF that is ∼10 times larger than the confocal parameter. The ability to extend the DOF without signal loss and sidelobe artifacts may ultimately overcome the DOF limitation in high-resolution OCT.

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 ∼25  dB 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.

Multifiber angular compounding optical coherence tomography for speckle reduction

We report on an integrated fiber optic design to implement multifiber angular compounding optical coherence tomography, which enables angular compounding for speckle reduction. A multi-facet fiber array delivers three light beams to the sample with different incident angles. Back-reflective/back-scattered signals from these channels were simultaneously detected by a three-channel spectrometer. The axial and lateral resolution was measured to be ∼3 and ∼3.5  μm, respectively, in air with ∼100  dB sensitivity. We conducted ex vivo experiments on a rat esophagus to demonstrate a contrast to noise improvement of 1.58.

Multiple aperture synthetic optical coherence tomography for biological tissue imaging

An inherent compromise must be made between transverse resolution and depth of focus (DOF) in spectral domain optical coherence tomography (SD-OCT). Thus far, OCT has not been capable of providing a sufficient DOF to stably acquire cellular-resolution images. We previously reported a novel technique named multiple aperture synthesis (MAS) to extend the DOF in high-resolution OCT [Optica4, 701 (2017)]. In this technique, the illumination beam is scanned across the objective lens pupil plane by being steered at the pinhole using a custom-made microcylindrical lens. Images captured via multiple distinctive apertures were digitally refocused, which is similar to synthetic aperture radar. In this study, we applied this technique for the first time to image both a homemade microparticle sample and biological tissue. The results demonstrated the feasibility and efficacy of high-resolution biological tissue imaging with a dramatic DOF extension.