| dc.description.abstract | Optical coherence tomography (OCT) is a label-free optical imaging technique that provides noninvasive visualization of biological tissue microstructures with micrometer-scale resolution and millimeter-scale penetration depth. OCT has become a well-established commercial product in ophthalmology due to its capability for noncontact and real-time imaging of ocular structures. Current research in OCT primarily focuses on applications in various biological and medical fields, alongside advancements in OCT system design. In this dissertation, we developed and applied multi-contrast OCT systems for early cancer detection, anticancer therapy monitoring, human organ transplantation viability evaluation, and aging vascular characterization.
In Chapter 1, I introduce the principle and development of the OCT system. I describe the systematic structure of multiple contract OCT systems including time-domain OCT (TD-OCT), spectral-domain OCT (SD-OCT), swept-source OCT (SS-OCT), doppler OCT (D-OCT), polarization-sensitive OCT (PS-OCT), and OCT angiography (OCTA) and their detecting principles in light-tissue interaction. Moreover, I outline the various biomedical applications based on these multi-contract OCT systems in this dissertation.
In Chapter 2, I discuss the application of SS-OCT on the classification of various in vitro MCTS, specifically focusing on drug screening and therapy monitoring. Multicellular tumor spheroid (MCTS) is a vital tool for in vitro study of anticancer drug screening and therapeutic effect monitoring. I proposed an anticancer therapy monitoring and drug screening platform using OCT imaging to reveal the longitudinal change of MCTS in morphological volume, internal microstructure, and internal microenvironment under the cell culture at different cell number, cell type, and drug treatment. With the applying of intrinsic attenuation contrast, uniformity degree, superficial-spatial-feature, and machine learning, OCT revealed that OCT intensity images can effectively distinguish OVCAR-8 MCTS with 5,000 and 50,000 cell culturing, Pan02-H7 MCTS with fibroblast cell culturing at 2:1, 1:1, and 1:2 ratios, and OVCAR-4 MCTS treated by 2-ME, AZD, and R-ke with a concentration of 1, 10, and 25 M.
In Chapter 3, I describe the application of PS-OCT on the detection and surgical guidance of early-stage renal tumor resection. Malignant tumors can significantly alter internal microstructural architecture and tissue properties. PS-OCT can distinguish between cancerous and normal renal tissues, as well as identifying specific types of renal tumors by detecting fibrosis and microstructural distributions. This PS-OCT-based early kidney tumor detection platform accurately delineates the boundary between cancerous and normal renal tissues, providing real-time surgical guidance for surgeons during tumor resection.
In Chapter 4, I describe the application of PS-OCT on pre-transplantation viability assessment of deceased human donor organs. Human organ transplant represents the final resort for patients suffering from advanced-stage diseases affecting vital organs such as the kidney, liver, and lung. However, a global shortage of donor organ sources has resulted in many patients dying while awaiting transplantation due to prolonged waiting times. We developed a human organ viability evaluation system based on PS-OCT to provide pre-transplantation assessment of deceased donor organs to increase the donor pool. By grading the histological performance of tissues from various regions within whole human organs, I have demonstrated that the biopsy performance of kidney, liver, and lung tissues is associated with specific areas, and that histological distribution is heterogeneous. I discovered that PS-OCT can detect volumetric tubule microstructures and quantify their distribution across the kidney through deep learning segmentation. Additionally, PS-OCT exhibits a strong correlation with histological scores, enabling the provision of fibrosis distribution and quantification. Moreover, I utilized PS-OCT to monitor volumetric steatosis microstructures throughout the entire liver, employing Sauvola segmentation for distribution quantification. PS-OCT has also proven effective in detecting and quantifying the distribution of hepatic fibrosis through linear fitting with biopsy results. Furthermore, PS-OCT can accurately detect alveolar size, density, and wall thickness, facilitating the quantification of their distribution across the entire lung. Our results underscore the capability of PS-OCT to identify crucial microstructures and tissue properties within human organs, offering a more comprehensive assessment of organ viability compared to conventional biopsy techniques.
In Chapter 5, I discuss the application of OCT angiography (OCTA) on the characterization and quantification of microvasculature of aging. Aging is a key factor in neural degeneration and plays a critical role in several diseases. I developed an aging microvascular imaging system by OCTA and two-photon microscopy (TPM) to monitor the change of mice cerebral microvasculature in various dimensions at different age stages. I discovered that OCTA and TPM can effectively compensate for the limitation of resolution and field-of-view (FOV) from single imaging modality, and quantify the difference of cerebral microvasculature in diverse dimensions at various ages. OCTA and TPM can achieve a more comprehensive analysis of mice cerebral blood vessels.
In Chapter 6, I describe the application of SS-OCT on the application of axial ocular structure detection for chick myopia monitoring. Chicks are an excellent model for studying myopia and its auto-recovery progress. I investigated the axial length (AL) and the thickness of different ocular structures in chicks’ eye undergoing visually induced changes using a SS-OCT system in vivo. I found that SS-OCT can serve as a promising tool to provide measurements of the entire ocular structures, for evaluating the change of thickness and depth of different ocular structures in chicks in vivo. The change of AL in the myopic and recovered chick eyes can be attributed to the thickness alterations of different ocular structures.
In summary, I utilized multi-contrast OCT systems, including SS-OCT, PS-OCT, and OCTA along with advanced imaging processing methods, to establish platforms for early cancer detection, monitoring anticancer therapy, assessing human organ transplantation viability, imaging microvascular changes associated with aging, and detecting the global ocular alterations in the chick myopia. Our applications demonstrated the efficacy of these OCT-based platforms in guiding surgical resection of renal tumors, evaluating therapeutic effects on MCTS, assessing pre-transplantation viabilities of deceased donor kidneys, livers, lungs, and quantifying vascular changes in the aging brain, and measuring the global alteration of chick eyes in myopia. These versatile multi-contrast OCT-based platforms hold significant potential for further development, promising broader applications in the realms of cancer research, therapeutic interventions, organ transplantation, aging, and ophthalmology studies. | en_US |
