We report a pioneer clinical study using triple-input polarization-sensitive optical coherence tomography (TRIPS-OCT) to assess sub-macular scleral birefringence in 60 children with myopia. Results showed a significant difference in scleral birefringence between high and low myopia groups. In addition, we observed a correlation between axial length and birefringence in the low myopia group. This suggests the potential of using sub-macular scleral birefringence as a biomarker for myopia progression. Despite a high exclusion ratio due to inadequate scleral visibility and other limitations, these findings warrant further large-scale studies.
Polarization-sensitive OCT (PS-OCT) derives image contrast from tissue birefringence. Here, we introduced triple-input polarization sensitive optical coherence tomography (TRIPS-OCT), a new polarimetric modulation and reconstruction strategy for depth-resolved tomographic birefringence imaging in-vivo. We modulated the polarization states between three repeated frames and enabled the reconstruction of the Mueller matrix at each location within the triple-measured frames. We demonstrated a 2-fold reduction of the birefringence noise floor compared to the conventional dual-input reconstruction method, and a 3-fold reduction of the measurement error of optic axis orientation in retinal imaging with the compensation of corneal retardance and diattenuation.
In frequency-domain optical coherence tomography (OCT) only half of the available depth range is used. This is due to the occurrence of complex conjugate (CC) ambiguity, which is an artifact resulting from the symmetry properties of the Fourier transform on real-valued spectrum that undermines the optimal sensitivity window. Current approaches require additional active or passive components, and increase systems complexity and cost. We present a novel deep-learning method for CC removal (CCR) based on a generative adversarial network (GAN). The model was trained to learn how to translate OCT scans with CC artifacts into full range images without the requirement of additional equipment or measurement. The data was collected from a phantom sample and human skin in vivo, using a swept source-OCT prototype. The GAN architecture adopted is based on the Pix2Pix model, where the discriminator is a PatchGAN and the generator is a U-net with skipped connections, and has been adapted for high resolution images of 864 × 1024 pixels. CCR-GAN receives as input the complete OCT signal, which consists of intensity and phase images. The findings and the evaluation metrics show that our model is able to effectively suppress CC artifact in OCT scans thereby providing a doubled imaging range. We demonstrated that our model is superior to prior approaches with respect to design complexity, imaging speed, and cost. CCR-GAN can be effectively used to suppress the CC mirror terms and generate full depth range in clinical imaging, that requires large ranging depth and high sensitivity.
KEYWORDS: Optical coherence tomography, Polarization, Ranging, Space mirrors, Range imaging, Demodulation, Phase shifts, Fourier transforms, Mirrors, In vivo imaging
In Fourier domain OCT, the depth profile is mirrored about the zero delay, limiting the imaging depth to half of the entire ranging space. We present a novel configuration for OCT to robustly remove the complex conjugate artifact. Our method utilizes the intrinsic delay of circularly polarized light in two polarization channels, using only passive broadband polarization optics and conventional polarization diversity detection unit. Our method is immune to sample motion and adds no restrictions to source bandwidth, imaging speed or computational load. 45 dB suppression of the mirror artifact is demonstrated by an SSOCT with some in-vivo images.
Flexible fiber-optic based imaging probes have significantly broadened the clinical application scope of optical coherence tomography (OCT), enabling high-resolution imaging of several regions in human body. The movement of flexible catheter causes the asymmetries of fiber geometry and stress, resulting in the presence of fiber birefringence. Scanning and flexing of the OCT probes results in variations in the polarization states of light from the sample arm. When the polarization states of light from the sample are misaligned with those of the reference arm, the interference fringes would fade out, leading to intensity variations and SNR degradation in OCT images.
From the statistical view, we characterized the intensity fluctuation and average signal-to-noise ratio (SNR) loss induced by the fringe fading of the sample arm polarization randomization. By taking advantage of an interesting observation, that the output polarization states of round-trip sample arm SMF are not uniformly distributed on the Poincare sphere, an optimum polarization state of reference arm can be found for the Michelson-type OCT configuration. From our analysis, we also suggested that the light source with low degree of polarization such as super-continuum source, or light source with long fiber, should be carefully managed to achieve the optimal SNR. We demonstrated our optimal polarization management, using two additional polarizers, could statistically provide 3.5 dB increase in system sensitivity.
Optical coherence tomography (OCT) provides high resolution and cross-sectional images of biological tissue and is widely used for diagnosis of ocular diseases. However, OCT images suffer from speckle noise, which typically considered as multiplicative noise in nature, reducing the image resolution and contrast. In this study, we propose a two-step iteration (TSI) method to suppress those noises. We first utilize augmented Lagrange method to recover a low-rank OCT image and remove additive Gaussian noise, and then employ the simple and efficient split Bregman method to solve the Total-Variation Denoising model. We validated such proposed method using images of swine, rabbit and human retina. Results demonstrate that our TSI method outperforms the other popular methods in achieving higher peak signal-to-noise ratio (PSNR) and structure similarity (SSIM) while preserving important structural details, such as tiny capillaries and thin layers in retinal OCT images. In addition, the results of our TSI method show clearer boundaries and maintains high image contrast, which facilitates better image interpretations and analyses.
Polarization sensitive optical coherence tomography (PS-OCT) is increasingly used in a range of applications, both in bench-top and catheter-based imaging configurations. Reconstruction of tissue birefringence is subject to many system and processing-dependent artifacts. However, methods for the calibration and validation of PS-OCT are missing. Here, we report on a method to fabricate tissue-like imaging phantoms exhibiting clearly defined regions with controllable amounts of birefringence. We employed the photoelastic effect to enable the generation of controllable amounts of stress-induced birefringence in rubber samples, verified with polarized light microscopy. Pigmented ink was added to liquid latex solution to mold and cure rubber bands with controlled backscattering and transparency. Differently stretched segments were embedded in a stress-free background matrix to generate clearly defined areas with high birefringence contrast in an area of homogenous backscatter intensity. Arranged in planar geometry or on the outside of a glass capillary, the stretched rubber bands defined phantoms for bench-top and catheter-based imaging, respectively. Segmentation of the defined regions of interest in the reconstructed volumetric birefringence tomograms enabled assessing measurement consistency, between repeated imaging with a single system, or between independent imaging systems.
Consistent and durable imaging phantoms are crucial for advancing PS-OCT imaging technology. Our tissue-like imaging phantoms exhibit clearly defined regions with controlled amounts of birefringence and facilitate testing, calibration, and validation of imaging systems and reconstruction strategies.
The evaluation of the endothelium coverage on the vessel wall is most wanted by cardiologists. Arterial endothelial cells play a crucial role in keeping low-density lipoprotein and leukocytes from entering into the intima. The damage of endothelial cells is considered as the first step of atherosclerosis development and the presence of endothelial cells is an indicator of arterial healing after stent implantation.
Intravascular OCT (IVOCT) is the highest-resolution coronary imaging modality, but it is still limited by an axial resolution of 10-15 µm. This limitation in axial resolution hinders our ability to visualize cellular level details associated with coronary atherosclerosis. Spectral estimation optical coherence tomography (SE-OCT) uses modern spectral estimation techniques and may help reveal the microstructures underlying the resolution limit. In this presentation, we conduct an ex vivo study using SE-OCT to image the endothelium cells on the fresh swine aorta. We find that in OCT images with an axial resolution of 10 µm, we may gain the visibility of individual endothelium cells by applying the autoregressive spectral estimation techniques to enhance the axial resolution. We believe the SE-OCT can provide a potential to evaluate the coverage of endothelium cells using current IVOCT with a 10-µm axial resolution.
Plaque rupture is the critical cause of cardiovascular thrombosis but this process is still under discussion. Recent studies show that, during crystallization, cholesterol crystals in atheromatous plaques accumulate rapidly in a limited space and may result in plaque rupture. However, the actual role of cholesterol crystals on plaque rupture remains unclear due to the lack of detailed morphological information of cholesterol crystals. In this study, we used a Micro-optical coherence tomography (µOCT) setup with 1-2 µm spatial resolution to extract the geometry of cholesterol crystals from human atherosclerotic artery ex vivo firstly. With measured dimensions of cholesterol crystals by this µOCT system (the average length and thickness of 269.1±80.16 µm and 3.0±0.33 µm), we developed a two-dimensional mechanical model in which rectangular shaped cholesterol crystals distribute at different locations spatially. We predicted the stress on the thin cap induced by the expansion of cholesterol crystals by use of finite-element method. Since a large portion of plaques (58%) rupture at points of peak circumferential stress (PCS), we used PCS as the primary indicator of plaque stability with blood pressure of 14.6 kPa on the lumen. The results demonstrate that loading of the concentrated crystals especially at the cap shoulder destabilize the plaque by proportionally increasing the PCS, while evenly distributed crystals loading along the cap might impose less PCS to the plaque than the concentrated case.
The sample 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 an axial resolution improvement method by using the autoregressive spectral estimation technique to instead of the inverse Fourier transform to analyze the spectral interferograms, which is named as spectral estimation OCT (SE-OCT). SE-OCT improves the axial resolution by a factor of up to 4.7 compared with the corresponding FD-OCT. Furthermore, SE-OCT provides a complete sidelobe suppression in the point-spread function. Using phantoms such as an air wedge and micro particles, we prove the ability of resolution improvement. To test SE-OCT for real biological tissue, we image the rat cornea and demonstrate that SE-OCT enables clear identification of corneal endothelium anatomical details ex vivo. We also find that the performance of SE-OCT is depended on SNR of the feature object. To evaluate the potential usage and define the application scope of SE-OCT, we further investigate the property of SNR dependence and the artifacts that may be caused. We find SE-OCT may be uniquely suited for viewing high SNR layer structures, such as the epithelium and endothelium in cornea, retina and aorta. Given that SE-OCT can be implemented in the FD-OCT devices easily, the new capabilities provided by SE-OCT are likely to offer immediate improvements to the diagnosis and management of diseases based on OCT imaging.
High-resolution optical coherence tomography (OCT) is of critical importance to disease diagnosis because it is capable of providing detailed microstructural information of the biological tissues. However, a compromise usually has to be made between its spatial resolutions and sensitivity due to the suboptimal spectral response of the system components, such as the linear camera, the dispersion grating, and the focusing lenses, etc. In this study, we demonstrate an OCT system that achieves both high spatial resolutions and enhanced sensitivity through utilizing a spectrally encoded source. The system achieves a lateral resolution of 3.1 μm and an axial resolution of 2.3 μm in air; when with a simple dispersive prism placed in the infinity space of the sample arm optics, the illumination beam on the sample is transformed into a line source with a visual angle of 10.3 mrad. Such an extended source technique allows a ~4 times larger maximum permissible exposure (MPE) than its point source counterpart, which thus improves the system sensitivity by ~6dB. In addition, the dispersive prism can be conveniently switched to a reflector. Such flexibility helps increase the penetration depth of the system without increasing the complexity of the current point source devices. We conducted experiments to characterize the system’s imaging capability using the human fingertip in vivo and the swine eye optic never disc ex vivo. The higher penetration depth of such a system over the conventional point source OCT system is also demonstrated in these two tissues.
We developed a spectral domain optical coherence tomography (SD-OCT) system employing dual-balanced detection (DBD) for direct current term suppression and SNR enhancement, especially for auto-autocorrelation artifacts reduction. The DBD was achieved by using a beam splitter to building a free-space Michelson interferometer, which generated two interferometric spectra with a phase difference of π. These two phase-opposed spectra were guided to the spectrometer through two single mode fibers of the 8 fiber v-groove array and acquired by ultizing the upper two lines of a three-line CCD camera. We rotated this fiber v-groove array by 1.35 degrees to focus two spectra onto the first and second line of the CCD camera. Two spectra were aligned by optimum spectrum matching algorithm. By subtracting one spectrum from the other, this dual-balanced detection system achieved a direct current term suppression of ~30 dB, SNR enhancement of ~3 dB, and auto-autocorrelation artifacts reduction of ~10 dB experimentally. Finally we respectively validated the feasibility and performance of dual-balanced detection by imaging a glass plate and swine corneal tissue ex vivo. The quality of images obtained using dual-balanced detection was significantly improved with regard to the conventional single-detection (SD) images.
KEYWORDS: Cameras, Optical coherence tomography, In vivo imaging, Signal to noise ratio, Image resolution, Imaging systems, Mirrors, Electrons, Spectral resolution, Near infrared
We developed a spectral domain OCT system combining two NIR, CW light sources of different spectral range. Its resolving power is validated by visualizing the cellular structures of zebra fish larvae in vivo. An NIR extended illumination from 755-1100 nm is achieved. The axial resolution is 1.27 μm in air, corresponding to 0.93μm in tissue (n=1.36), which is the highest axial resolution using NIR, CW laser sources up to date to the best of our knowledge. In vivo imaging is conducted to demonstrate the resolving power of proposed one-micron resolution OCT system. The top and bottom surfaces of individual disk-like red blood cell is reliably visualized, as well as flat, spindle shaped endothelial cells lining along the luminal surface of the blood vessel wall. This study provides a viable solution for cellular and subcellular level OCT imaging system which is also very competitive in cost.
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