Graduation Year

2022

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Electrical Engineering

Major Professor

Ashwin B. Parthasarathy, Ph.D.

Committee Member

Andrew Hoff, Ph.D.

Committee Member

Stephen Saddow, Ph.D.

Committee Member

Robert Frisina, Ph.D.

Committee Member

Ann Eddins, Ph.D.

Keywords

Blood Flow, Blood Oxygenation, Modulation, Multi-frequency

Abstract

Tissue oxygen saturation, blood flow and blood volume are physiological bio-markers of tissue health. Diffuse Optical Spectroscopy(DOS) and Diffuse Correlation Spectroscopy (DCS) are two complementary approaches to measure tissue oxygen saturation and blood flow respectively. Quantitative Diffuse Optical Spectroscopy (DOS) uses multi-spectral intensities of near-infrared light that have been modulated at RF frequencies to estimate static tissue optical properties and hence concentrations of oxygenated and de-oxygenated hemoglobin. Diffuse Correlation Spectroscopy estimates tissue dynamics - i.e., blood flow, by measuring temporal intensity auto-correlation function of backscattered light diffusing through the tissue. Conventionally, DCS instruments use coherent light sources with constant intensity. This dissertation focuses on applying frequency domain methods to DOS and DCS to improve measurement fidelity and reduce systemic errors prevalent in current technology. To this end, I introduce a new broadband heterodyne demodulation technique for multi-frequency frequency domain DOS (FD-DOS) and a novel frequency domain DCS (FD-DCS) technique to estimate tissue oxygenation and blood flow index from a single measurement. First, I demonstrate a frequency domain DOS system that measures amplitude and phase of diffuse photon density waves at different source-modulating frequencies and a single source-detector separation. This multi-frequency FD-DOS system reduces measurement errors due to the partial volume effects and overcomes the major drawbacks in the conventional frequency domain DOS instruments that operate at a single modulation frequency. Critically, the (heterodyne) demodulation is performed using off-the-shelf RF components, which decreases instrument size, reduces complexity and increasing the data acquisition rate without requiring large data sets. I validate this new method with controlled experiments on tissue simulating phantoms and in-vivo experiments. In the second part of the dissertation, I extend the multi-frequency aspect to DCS and develop a novel technique - Frequency Domain Diffuse correlation Spectroscopy(FD-DCS). FD-DCS uses intensity modulated light source at RF frequencies to measure frequency dependent intensity auto correlation functions and estimate static and dynamic optical properties of the tissue at a single source-detector separation in a single measurement. FD-DCS system can be easily executed by modifying the source of conventional DCS system to a RF modulated source. I derive a new general photon diffusion model that describes tissue light propagation and a new frequency domain solution for diffuse correlation density waves (DCDW). I built a bench-top prototype, and validated this new theory with experiments on tissue simulating phantom experiments. FD-DCS eliminates the measurement errors caused by differences in tissue sampling volumes and source-detector positions of DOS and DCS systems, thereby eliminating the need for hybrid DOS-DCS system.

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