Developments in Modeling and Analysis of Interferometric Spectroscopic Imaging


Optical microscopy is one of the most ubiquitous tools for functional imaging of biological phenomena. While relatively non-destructive to living organisms, light microscopy’s spatial resolution is diffraction limited, restricting the minimum resolvable features. On the other hand, high resolution techniques such as electron microscopy or STORM, have several orders of increased imaging resolvability at the expense of destructive sample preparation, induced phototoxicity, and altered molecular structure. Utilizing hyperspectral interference-based imaging, a plethora of descriptive statistics can be extracted from the sample’s scattering profiles to describe subdiffractional architecture and molecular content, all while reducing destructive, chemical, and phototoxic exposure. However, it is challenging to construct biologically mimicking phantoms with precise nanoscale level structures for methodological characterization, optimization, and validation of novel imaging devices or biomarkers. This thesis seeks to circumvent this issue by using the Finite Difference Time Domain (FDTD) simulation method to model various aspects of human cellular architecture and molecular composition with nanometer resolution in order to expand upon previously established techniques in spectroscopic imaging. In the scope of this dissertation, two systems that utilize spectroscopic interference for higher dimensional analysis were explored: Spectroscopic Optical Coherence Tomography (SOCT) and Partial Wave Spectroscopy (PWS). Although their system geometries are quite different, their theoretical frameworks are similarly based in the principles of scattering theory and modulated through the "lens" of their system-based transfer functions. For both of these imaging systems, first, I developed a theoretical framework to relate biological ultrastructure via its mass-density distribution to the backscattering spectrum. Then, using FDTD, this theoretical framework was validated and expanded to characterize the effect of various geometries of common optical microscopy systems. Finally, live-cell imaging experiments using PWS and in-vivo human tissue imaging with SOCT demonstrated the validity of the models used and assumptions made in establishing the theory. Developing highly robust modeling techniques with minimal assumptions to further understand the inverse scattering problem for complex biologically mimicking media has a wide range of research, discovery and clinical based applications.

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