Development of cellular resolution optical coherence tomography

• Main Author: Bo, En
• Other Authors: Liu Linbo
• Format: Theses and Dissertations
• Language: English
• Published: 2019
• Subjects: DRNTU::Engineering::Bioengineering
• Online Access: https://hdl.handle.net/10356/81264; http://hdl.handle.net/10220/47468
• Institution: Nanyang Technological University

Diagnosis of most mucosal diseases including epithelial cancers relies on white-light endoscopy/visual inspection followed by random biopsy and histologic examination. These current standard-of-care tools are associated with many issues such as sampling errors, tissue destruction, and processing artifacts. In addition, it is too traumatic to take a biopsy from tissues like eyes and coronary arteries. Being high resolution, high speed, and non-invasive, optical coherence tomography (OCT) has emerged as an endoscopic and intravascular imaging tool that provides valuable anatomic information complementary to the standard-of-care techniques. However, it has a typical resolution of 10 μm, which is too coarse to visualize most cellular structures. Micro-optical coherence tomography μOCT provides spatial resolutions of 1~2 um to visualize microstructures at the cellular and sub-cellular level. One of the major inherent issues with the current μOCT imaging systems is the limited depth of focus (DOF). The DOF, defined as the confocal parameter in the classical theory of Fourier domain OCT (FD-OCT), is proportional to the square of the transverse resolution. Consequently, a trade-off occurs between the transverse resolution and the DOF in which a lower transverse resolution results in a larger DOF and vice versa. Another two of the major inherent issues with current μOCT imaging systems are the auto-correlation artifacts (ACA) and complex conjugate artifacts (CCA). ACA originates from the interference between sample reflectors or scatters of different depths; CCA arises from the fact that the current μOCT system can only detect the real part of the complex interferometric signal. The main objective of this research is to develop novel optomechanical techniques and apparatus to overcome the above-mentioned issues with OCT to facilitate its clinical applications. The main contribution of this thesis is the development and validation of multiple aperture synthesis (MAS) techniques and imaging systems to overcome the aberrations of the imaging system such as defocus and those from the turbid tissue. MAS is a kind of digital refocusing technique, which is analogous to synthetic aperture radar (SAR). The key technology of MAS is the implementation of aperture division and the multiplexing apparatus. In the first attempt, a micro cylindrical lens driven by a piezoelectric transducer (PZT) is employed to demonstrate the feasibility of DOF extension without signal loss and sidelobe artifacts, but at the cost of imaging speed. In the second attempt, a mirror with two surfaces coated is employed to achieve the same DOF extension purpose without sacrificing the imaging time. In the third attempt, I design and develop a calcite beam displacer based MAS apparatus for overcoming defocus and aberrations induced by turbid tissue, which has the potential to scale down and be miniaturized in an endoscopic fiber probe. The proposed MAS techniques may ultimately overcome the inherent trade-off between DOF extension, signal loss/sidelobe artifacts/imaging speed in high-resolution OCT. Additionally, I develop a novel homemade dual-channel spectrometer by employing two lines of a three-line camera to suppress ACA and CCA. For ACA suppression, two interferometric spectra with a phase difference of π are detected by the dual-channel spectrometer simultaneously. ACA is suppressed by counterbalance signals obtained from dual channels. For CCA suppression, two interferometric spectra with a phase difference of 2π/3 are detected by the dual-channel spectrometer simultaneously. The complex interferometric signal is reconstructed by trigonometric manipulation of two real interferometric spectra, and then ACA is suppressed by use of inverse Fourier transform. The problems of limited DOF, turbid tissue induced aberration, and fundamental ACA and CCA are addressed in this thesis, which enables us to visualize imperceptible changes in cellular and sub-cellular resolution, and evaluates pathological lesion in an early period by characterizing the cellular and sub-cellular morphology of human tissues. All the novelties enable this project to play a potential role in the clinical practice of disease diagnosis and treatment, especially for gastrointestinal cancer, epithelial cancer, and atherosclerosis.