Ultrahigh resolution spectral domain optical coherence tomography and its functional extension for human myocardium and breast tissue imaging

Over the past 25 years of development and innovation, optical coherence tomography (OCT) has successfully fills the gap between the ex vivo high-resolution optical microscopy technologies and in vivo low-resolution medical imaging modalities, including computed tomography (CT), magnetic resonance imaging (MRI), ultrasound (US). Ultrahigh resolution (UHR) OCT categorizes OCT systems with an axial resolution below 3 µm in tissue. With the improved resolution, UHR OCT may impart the knowledge of detailed structures of the tissues that are almost close to what histology may provide. This is how UHR OCT can act as a bridge between radiology and histology. This thesis will present an ultrahigh-resolution (UHR) spectral domain (SD) OCT system that features both high axial resolution and long imaging range, and will demonstrate its applications in human myocardium and breast tissue imaging. The UHR OCT system accommodates a supercontinuum light source, and a home-built spectrometer designed to achieve optimized imaging performance. Specifically, the spectrometer features a customized focusing lenses that are comprised of off-the-shelf optics and a 2k-pixel camera to minimize the cost of the instrument. The system manifests an axial resolution of 2.72 µm and a lateral resolution of 5.52 µm, with a large imaging range of 1.78 mm. The sensitivity of the system is 93 dB with a 6-dB sensitivity fall-off range of 0.89 mm. For human myocardium, currently there is no high-resolution non-destructive real-time imaging modality available for biopsy guidance. As a real-time and non-destructive imaging tool, UHR OCT offers additional benefits compared with standard OCT, which are illustrated by successful delineation of micro-structures such as thin elastic fibers and Purkinje fibers in the endomyocardial side. These structures are otherwise not visible within standard-resolution OCT images. Moreover, by adding the cross-polarization (CP) functionality to the UHR SD system, different types of myocardial tissue can be better delineated through the CP contrast. The functional information provided by CP-OCT may also facilitate automatic tissue classification by using A-line signals. For breast tissue imaging, we show qualitatively and quantitatively that UHR OCT images may enable better visualization of detailed features in different types of breast tissue, including healthy and cancerous ones. UHR OCT images of new breast cancer types such as phyllodes tumor, necrotic tumor and fibrotic focus carcinoma are provided for future references. Features developed from UHR OCT images enable a better yield from relevance vector machine (RVM) based stochastic classification model, compared with that from standard resolution OCT images. UHR OCT shows a great promise for automated classification of different tissue types in human breast tissue based off on UHR OCT images. Lastly, we present our endeavor to miniaturize the UHR OCT system on chip. We explore a chip-based optical frequency comb source that may enable UHR OCT at longer wavelengths to achieve better signal penetration in the future. We characterize the performance of the novel source, including the axial resolution and noise, and show that it holds the promise to be adopted in UHR OCT imaging. In addition, we also demonstrate an on-chip tunable reference arm that allows high-topology high-resolution OCT imaging. The compactness of the devices pave the way to the ultimate miniaturization of OCT system