Advances in Optical Coherence Tomography and Microscopy for endoscopic applications and functional neuroimaging

Optical Coherence Tomography (OCT) is a developing medical imaging technology that generates micron resolution cross-sectional images of subsurface internal tissue structure in situ and in real time, without the need to remove and process specimens. Previous studies have suggested that OCT holds great potential for use in laparoscopic and endoscopic applications to detect early stage neoplastic pathologies. A minimally invasive imaging modality capable of identifying pre-malignant tissues in vivo could be used to guide conventional excisional biopsy and histology, thereby reducing sampling error and enabling earlier detection and treatment. One limitation of prior endoscopic OCT imaging methods is the inability to visualize cellular features characteristic of early disease states such as neoplasia. This thesis seeks to demonstrate that advances in OCT resolution and in miniaturized imaging devices will lead to enhanced visualization of pathologic changes in vivo at both the tissue architectural and cellular levels. Toward this goal, three technological advances are made. First, compact and portable laser light sources for clinical ultrahigh resolution OCT are demonstrated based on supercontinuum generation in highly nonlinear optical fibers. Second, an extension of OCT called optical coherence microscopy (OCM) is developed for in vivo cellular imaging. High speed OCM system designs are demonstrated and characterization of OCM imaging parameters is performed. Importantly, this work demonstrates that OCM can make use of broadband laser sources to image cellular features with reduced numerical aperture compared to confocal microscopy, thereby facilitating the development of small diameter endoscopic probes. Third, two-axis scanning catheters based on micromirror technology are designed and demonstrated for ultrahigh resolution threedimensional and en face OCT imaging. To demonstrate feasibility of these advances in future clinical applications, ex vivo imaging studies of endoscopically accessible human gastrointestinal tissues including key pathologies are performed. Results demonstrate that three-dimensional and cellular resolution optical coherence imaging can significantly improve performance over conventional OCT methods for gastrointestinal endoscopy. Finally, this thesis also explores a new application for optical coherence tomography in neuroscience. Optical methods are currently being used to study the neurovascular response to functional activation, but most existing techniques lack depth resolution. Through correlation with video microscopy, OCT is shown to enable depth-resolved cross-sectional imaging of functional activation in the important rat somatosensory cortex model system. With further development, OCT may offer a new tool for basic and applied neuroscience research. Thesis Supervisor: James G. Fujimoto Professor of Electrical Engineering and Computer Science