Dissertation Defense: Zuzana Adams, "Multi-modal Tabletop to Endoscopic Imaging: Development of Highly Miniaturized Optical Endoscopes"

High resolution, advanced imaging modalities such as Optical Coherence Tomography (OCT) and multi-photon microscopy (MPM) are clinically valuable tools for early detection of cancer. OCT provides structural information via cross-sectional images of tissue microstructure, and Multiphoton Microscopy (MPM) detects fluorescence from biological or exogenous molecules (Two- or Three-Photon Excited Fluorescence, [2PEF/3PEF]) as well as second harmonic generation (SHG) from collagen and Third Harmonic Generation (THG) from cell membranes and interfaces. Combined, these mechanisms of contrast can provide complimentary information to aid in clinical diagnosis and biomedical research.

 

This dissertation presents three studies into novel instrumentation for advanced and multimodal imaging. First, a compact, fiber-based, multi-modal table-top raster scanning microscope system is presented, capable of co-registered tri-modality imaging: 1) MPM with 1400 nm excitation, 2) high lateral resolution Optical Coherence Microscopy (OCM) at 1300 nm, and 3) Reflectance imaging at 561 nm. Sources are combined into a double-clad fiber (DCF), which transmits illumination through the core and collects return signal in the core and inner cladding, to be coupled to photomultiplier tubes, a linescan spectrometer, or a photodiode for the MPM, OCT, and reflectance modalities, respectively. The tabletop proximal system (sources, detectors, and coupling fibers) can be disconnected from the distal microscope enclosure (beam scanning and focusing components) and connected to a future endoscope, allowing seamless translation between benchtop and clinical form factors.

 

Second, a prototype 1.0 mm diameter flexible side-firing helically scanning endoscope is presented with a low numerical aperture (NA) lens for single-photon imaging. Third, a high NA lens system is detailed, suitable for multiphoton imaging applications. In both cases, the endoscope working length is comprised of a stationary outer sheath and an inner, proximally-driven, fiber optic-coupled optical system. The distal optical system is comprised of a 0.5mm monolithic multi-element lens system, 3D printed via two-photon polymerization (2PP), that employs a lens on the exit face of a custom prism. This configuration allows side-firing with either low or high numerical apertures; the latter necessary for multi-photon imaging. Characterization of both low and high NA lenses show performance similar to that predicted from optical modeling.