Development of Biodynamic Imaging for Phenotypic Profiling of Living Tissue

Biodynamic imaging (BDI) is a high-content optical imaging technology based on Fourier-domain digital holography and Doppler spectroscopy of intracellular dynamics. There are three main functions of the BDI technique, which are optical coherence imaging (OCI), motility contrast imaging (MCI) and tissue dynamics spectroscopy (TDS). OCI is related to en face optical coherence tomography (OCT) using partially coherent speckle generated by broad-area illumination with coherence detection through digital holography. MCI provides noninvasive functional imaging by treating intracellular motility as an endogenous dynamic imaging contrast agent. TDS produces broad-band Doppler fluctuation power spectra that contain the ensemble of all intracellular motions by collecting and extracting depth-resolved quasi-elastic dynamic light scattering from inside multicellular living tissue. This thesis presents the development and applications of BDI systems. Doppler spectral clustering analysis is demonstrated when comparing fresh canine lymphoma biopsies and their corresponding flash-Frozen samples. Doppler spectral phenotyping analysis is used to identify a non-predictive phenotype of TDS that shows a systemic red-shift of frequencies. Doppler spectral shift analysis is used to monitor bacterial infection of living tissue.