Disease diagnosis based on the visual inspection of the pathological presentations or symptoms on the epithelial tissue such as the skin are subjective and highly depend on the experience of the doctors. Vital diagnostic information for the accurate identification of diseases is usually located underneath the surface and its depth distribution is known to be related to disease progression. Although optical spectroscopic measurements are fast and non-invasive, the accurate retrieval of the depth-specific diagnostic information is complicated by the heterogeneous nature of epithelial tissues. The optical signal measured from a tissue is often the result of averaging from a large tissue volume that mixes information from the region of interest and the surrounding tissue region, especially from the overlaying layers. Our group has developed a series of techniques for depth sensitive optical measurements from such layered tissues. We will first review the earlier development of composite fiber-optic probe, in which the source-detector separation and the angles of source and detector fibers are varied to achieve depth sensitive measurements. Then the more recent development of non-contact axicon lens based probes for depth sensitive fluorescence measurements and the corresponding numerical methods for optimization will be introduced. Finally, the most recently developed snapshot axicon lens based probe that can measure Raman spectra from five different depths at the same time will be discussed. Results from tissue phantoms, ex vivo pork samples and in vivo fingernail measurements will be presented, which indicates the great potential of depth sensitive optical spectroscopy for clinical tissue diagnosis.
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.
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.
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.
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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