title: Multiple reference and nanosensitive optical coherence tomography
Creators: name: Arangath, Anand
Publisher: name: University of Galway
Year: 2024
Subjects: subject: Imaging
subject: Optical Coherence Tomography
subject: Biophotonics
subject: Optics
subject: Polarization
subject: Multiple Reference Optical Coherence Tomography
subject: Nanosensitive OCT
subject: Stemcell tracking
subject: Natural Sciences
subject: Physics

description: The commercial availability of miniaturized optics and the need for flexibility in many clinical applications have driven a desire for the reduction in OCT system form factor and cost while maintaining fit for purpose imaging performance. Multiple Reference Optical Coherence Tomography (MR-OCT) is a modified Time-Domain OCT with a partial mirror before the scanning reference mirror. MR-OCT unlocks opportunities to realize low-cost and miniature OCT for specific applications using off-the-shelf components and conventional production methods. In this thesis, our emphasis is on optimizing the imaging performance of MR-OCT and enhancing its capabilities by integrating a nanosensitive OCT algorithm designed to detect structural changes at the nanoscale level. First, to improve MR-OCT sensitivity, we implemented a digitally balanced detection scheme with a polarization-based optical configuration. Balancing the signals in the digital domain increased the efficiency of common-mode rejection and presented an average sensitivity improvement of 5 ± 0.5 dB over its analogue balanced detection counterpart. The superior sensitivity of digitally balanced detection helped to increase the image contrast in Scotch tapes and mouse eyes. Additionally, in the context of the polarization-based optical configuration, we modelled the properties of the MR-OCT signal for a birefringent sample. We show that the quarter-wave plate in the sample arm of the Michelson interferometer can be adjusted to optimize the signal returning from a birefringent sample, thereby improving the visibility of structures of interest. The theory and techniques discussed in this study will be helpful for a wider OCT community to understand and minimize signal degradation due to birefringence in Time-Domain and Fourier-Domain OCT systems. Next, we implemented nanosensitive optical coherence tomography (nsOCT) in the MROCT system. Nanosensitive OCT (nsOCT) is a technique that enables OCT systems to detect nanoscale structural alterations. Incorporation of nsOCT advances the potential of MR-OCT without adding extra cost or form factor. Nanosensitive OCT uses the spectral encoding of the spatial frequency approach to extract high spatial frequency information in the signal originating from periodic structures. A theoretical basis for nsOCT is presented. We demonstrate that the integration of nsOCT with either Spectral Domain or MR-OCT enables the differentiation between two Bragg’s gratings with axial structures separated by approximately 10 nm. We also show the capability of nanosensitive MR-OCT to identify sub-micron structural changes resulting from an induced superficial alkali burn on an excised rabbit cornea. Finally, we used the nsOCT technique for detecting structural changes in stem cells. On imaging pellets of mesenchymal stromal cells following labelling with different concentrations of plasmonic gold nanostars, the nsOCT detected that the mean spatial period of MSC pellets increases after labelling with increasing concentrations of nanostars. In the study of the MSC pellets chondrogenesis differentiation model, the nsOCT results indicated that the spatial period increased during the progression in the formation of the precartilage condensation matrix and decreased during its transformation into an aggrecanrich cartilage matrix. We validated the spatial period changes identified by nsOCT by conducting a Fourier analysis on TEM and histology images obtained from corresponding samples.