Improving optical coherence tomography theories and techniques for advanced performance and reduced cost

Optical coherence tomography (OCT) has been developed as a high-resolution three-dimensional imaging technique for clinical diagnosis. This thesis proposes several theoretical discoveries and technical improvements to the current OCT systems aiming to drastically reduce system costs while achieving the state-of-the-art performance. Polarization-sensitive OCT (PS-OCT) is a functional extension of conventional OCT which offers the depth-resolved birefringence imaging capability. To resolve local retardation in tissue samples, the current PS-OCT system employs two multiplexed polarization states to illuminate the sample under investigation and detects the backscattered light with two detection channels. We observed that the polarization state of light after round-trip propagation through a birefringent medium frequently aligns with the employed input polarization state but "mirrored" by the horizontal plane of the Poincaré sphere. We explore the predisposition for this mirror state and demonstrate how it constrains the evolution of polarization states as a function of the round-trip depth into weakly scattering birefringent samples, as measured with PS-OCT. The constraint enables measurements of depth-resolved sample birefringence with PS-OCT using only one input polarization state, which offers a critical simplification and cost reduction compared to the use of multiple input states. We demonstrated the capability of polarization mirror state in local birefringence restoration with birefringent phantom imaging and swine retina imaging ex vivo. If we take transpose for both sides of the Jones transmission equation of a PS-OCT system with two input states and two detection channels, the mirror state constraint still holds while the input and output states exhibit interchangeability, which implies that depth-resolved birefringence imaging is possible with only one detection channel, if the sample is illuminated with two orthogonal polarization states. Considering the high cost of spectrometers and the difficulty of pixel alignment between two detection channels, the transposed mirror state constraint helps to cut the cost and complexity of spectral domain PS-OCT system. Inspired by the mirror state constraint, we realized that the polarization states of detected sample light, after propagating through a stochastically moving reciprocal optical path, would not distribute evenly on the Poincaré sphere, but tend to aggregate around the mirror state. This can be used to solve a long-standing problem that the detected interferograms of fiber-based OCT suffer from the fringe attenuation effect due to the polarization state mismatch between the light from the two interference arms which results in sensitivity deterioration and intensity fluctuation. This problem was conventionally solved by expensive polarization diverse detection. The polarization mirror states implies the existence of an optimal polarization state for the reference light. If the reference light is aligned with the polarization mirror state of the input light, a 3.5dB signal-to-noise ratio improvement is demonstrated without additional hardware costs. The axial resolution, being a critical parameter to the resolving power of OCT system, is determined by the light spectral shape and bandwidth. The pursuit of higher axial resolution leads to exponentially increasing system cost, and sometimes is even impossible because of the unavoidable gaps in the wavelength range of illumination, transmission, and detection. We demonstrate that the axial resolution deteriorated by gaps in OCT spectra can be restored by adopting the gapped amplitude and phase estimation (GAPES) method. The algorithm estimates the missing parts between separated spectral bands and obtains a tissue axial profile with reduced sidelobe artifacts and significantly improved axial resolution over the individual bands. This technique may make it possible to combine spectrally separated sources and detectors to improve axial resolution in OCT images, hence greatly reduce the cost of ultra-high-resolution OCT system. In conclusion, this thesis proposed methods to reduce the cost of current OCT system with advanced performances in terms of state-of-the-art contrast, sensitivity and resolution, which has been demonstrated with phantom imaging and biological tissue imaging.Doctor of Philosoph

Automatic differentiation of nonkeratinized stratified squamous epithelia and columnar epithelia through feature structure extraction using OCT

As a type of precancerous lesion, metaplasia is usually considered to be associated with developing cancer. In clinical practice, surveillance of metaplastic cases usually relies on excisional biopsy followed by histological processing and analysis. As it is an invasive method accompanied by other complications, non-invasive imaging methods such as optical coherence tomography (OCT) can complement the existing method by enabling large area scanning. However, because it takes time to review large amount of data acquired from the whole suspected mucosal areas, an automatic classification method is preferred to alleviate the laboring hours and to avoid ‘sampling errors’ during image analysis. In this study, we report an automatic method to differentiate non-keratinized squamous epithelia and columnar epithelia in OCT images. A high detection accuracy is achieved by using feature structure extraction techniques in intact tissues.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)Nanyang Technological UniversityNational Research Foundation (NRF)This research was supported in part by A*STAR Biomedical Research330 Council (H1701a008), National Natural Science Foundation of China (Grant331 No. 61705184), National Research Foundation Singapore (NRF-CRP13-332 2014-05), Ministry of Education Singapore (RG 83/18 (2018-T1-001-144)), and 333 NTUAIT-MUV program in advanced biomedical imaging (NAM/15005)

A two-step iteration mechanism for speckle reduction in optical coherence tomography

Optical coherence tomography (OCT) is an imaging tool that has been widely utilized for various disease diagnoses for its noninvasive and high-resolution properties. Due to the dual role of speckles in the imaging process, however, OCT images suffer from the unavoidable speckle noise, which is usually regarded to be multiplicative in nature and reduces image contrast and resolution. In this study, we propose to categorize OCT speckle noise into additive portion and multiplicative portion, and present a simple two-step iteration (TSI) mechanism to suppress such noises separately. With the augmented Lagrange minimization (ALM) method adopted to recover a low-rank image, the first step of TSI is to remove the additive Gaussian noise, while the second step of TSI is to suppress the multiplicative noise by employing a split Bregman method (SBM) to solve the total-variation (TV) de-noising problem. Extensive experiments with OCT images of the swine eye, human and rabbit retina are conducted to verify the effectiveness of the proposed method. Results show that the proposed TSI method outperforms the existing methods in different cases. Specifically, TSI helps improve the peak signal-to-noise ratio (PSNR) and structure similarity (SSIM) of the swine eye images from 17.19 dB to 33 dB and 0.12 to 0.92, respectively, with the important structural details well preserved. The clearer boundaries and higher image contrast obtained with the TSI method would largely facilitate image analyses and interpretations for the clinical applications of OCT systems.NRF (Natl Research Foundation, S’pore)MOE (Min. of Education, S’pore)NMRC (Natl Medical Research Council, S’pore)Accepted versio

Polarization management to mitigate misalignment-induced fringe fading in fiber-based optical coherence tomography

In fiber-based optical coherence tomography (OCT), the interference fringes suffer from the fading effect due to misalignment of the light polarization states between the reference and sample arms, resulting in sensitivity degradation and image intensity variation. We theoretically and experimentally analyzed the relation between the misalignment and the fading coefficient. Assuming that the variation of the light polarization in single-mode fiber (SMF) was a random process, we statistically quantified the fading effect. Furthermore, in OCT configuration based on the Michelson interferometer, we reported an interesting observation that the polarization states of light traveling a round-trip in SMF are not evenly distributed on the Poincare sphere. Based on this observation, we demonstrated the existence of an optimal output polarization state of the reference arm to mitigate the fading effect. We demonstrated that in an optimal setup, the statistical average signal-to-noise ratio could be 3.5 dB higher than a setup without proper polarization management.NRF (Natl Research Foundation, S’pore)MOE (Min. of Education, S’pore)NMRC (Natl Medical Research Council, S’pore)Published versio

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.NRF (Natl Research Foundation, S’pore)ASTAR (Agency for Sci., Tech. and Research, S’pore)MOE (Min. of Education, S’pore)NMRC (Natl Medical Research Council, S’pore)Accepted versio

Optical coherence tomography with gapped spectrum

The axial resolution of optical coherence tomography (OCT) is determined by the spectral shape and bandwidth of the detected light, which are limited by the gaps in the wavelength range of illumination, transmission, and detection. In this paper, we demonstrate that the axial resolution deteriorated by gaps in OCT spectra can be restored by adopting the gapped amplitude and phase estimation (GAPES) method. GAPES estimates the missing parts between separated spectral bands and obtains the axial profile of tissue with reduced sidelobe artifacts compared to the gapped spectra and significantly improved axial resolution over the individual bands. This technique may make it possible to combine spectrally separated sources and detectors to improve axial resolution in OCT images.Ministry of Education (MOE)National Medical Research Council (NMRC)National Research Foundation (NRF)Published versionThis work was supported inpart by the National Research Foundation Singapore under Grant NRF-CRP13-2014-05, in part by the National Medical Research Council Singapore under Grant NMRC/CBRG/0036/2013, in part by the Ministry of Education Singapore under Grant MOE2013-T2-2-107, and in part by the NTU-AIT-MUV program in advanced biomedical imaging under Grant NAM/15005

Design and optimization of a spectrometer for high-resolution SD-OCT

We report the design of a high-efficiency spectrometer for high-resolution spectral-domain optical coherence tomography (SD-OCT). The advantages of the proposed spectrometer are two-fold: first, we use a concave mirror instead of a camera lens (as typically used) as the focusing optics to both improve the transmission efficiency and eliminate chromatic aberrations; second, the efficiency of the proposed spectrometer is approximately 1.23 times that of a refractive optics-based spectrometer for an SD-OCT system, with comparable ranging depth and axial resolution. Both theoretical analyses and imaging experiments were conducted to characterize and validate the performance of the proposed spectrometer.Ministry of Education (MOE)Nanyang Technological UniversityNational Medical Research Council (NMRC)National Research Foundation (NRF)Accepted versionThis research was supported in part by the National Natural Science Foundation of China (Grant No. 61705184), the Natural Science Basic Research Plan in Shaanxi Province of China (Grant No. 2018JQ6014), the National Research Foundation Singapore (NRF-CRP13-2014-05), National Medical Research Council Singapore (NMRC/CBRG/0036/2013), Ministry of Education Singapore (MOE2013-T2-2-107), NTU-AIT-MUV program in advanced biomedical imaging (NAM/15005), and the Fundamental Research Funds for the Central Universities (Grant No. G2018KY0308)

Single input state polarization-sensitive optical coherence tomography with high resolution and polarization distortion correction

Abstract: In single input state polarization-sensitive optical coherence tomography (PS-OCT) with high resolution, the imperfections of quarter-wave plate (QWP) and the sensitivity roll-off mismatch between the two detection channels cause unpredictable polarization distortion. We present a correction method based on the Jones matrix modeling of the system. In a single input PS-OCT system working at 840 nm with an axial resolution of ~2.3 μm, the method yielded better estimation of retardation and optic axis orientation with significantly reduced noise level, especially in weakly birefringent samples. Numerical simulations and quantitative imaging of a sample of known birefringence were performed to validate the performance. We further demonstrate the advantages of our approach with birefringence imaging of swine retina, rat aortic wall, and rat esophageal mucosa for potential clinical applications.NRF (Natl Research Foundation, S’pore)ASTAR (Agency for Sci., Tech. and Research, S’pore)MOE (Min. of Education, S’pore)Published versio