Graduation Semester and Year

2021

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering

Department

Bioengineering

First Advisor

Hanli Liu

Abstract

Photobiomodulation (PBM) with near infrared light may become a non-invasive, effective clinical tool after it is understood well for its mechanism of action. In my dissertation research, I have addressed three research questions as three aims to achieve. Aim 1 was to investigate and demonstrate the reproducibility of the effects of transcranial PBM (tPBM) with 1064-nm laser delivered on the right forehead of separate groups of healthy humans measured using different experiment setups in separate sites and years. In Chapter 2, I reported sham-controlled, tPBM-induced concentration increases in oxygenated hemoglobin (∆[HbO]) and oxidized cytochrome c oxidase (∆[oxi-CCO]) in both young and older adults. Specifically, broadband near infrared spectroscopy (bb-NIRS) was utilized to record ∆[HbO] and ∆[oxi-CCO] in 15 young and 5 older healthy subjects before, during, and after 8-min tPBM. Statistical analysis showed that no significant difference existed in ∆[HbO] and ∆[oxi-CCO] during and post tPBM for the young adults between my current study and a previous one taken three years prior at a different site. The two age groups also showed statistically identical increases in sham-controlled effects of tPBM. In short, this chapter demonstrates the robust reproducibility of tPBM being able to improve cerebral hemodynamics and metabolism of the human brain in vivo in both young and older adults. In Aim 2, I investigated how 8-min, non-invasive tPBM with 1064-nm laser would modulate cerebral-electrophysiological signals and brain connectivity in the human cortex. In Chapter 3, I proposed a new hypothesis that right prefrontal tPBM enables to increase directional interactions of brain functional networks or so-called information flow (IFlow) mainly at alpha and beta frequencies across cortical regions. Data from 19 healthy humans were analyzed using the Granger-causality approach (i.e., eCONNECTOME, an open-source MATLAB package). With this computational tool, the sham-controlled, tPBM-induced changes in IFlow and respective locations were mapped onto the dipole and cortical space at the group level during and after tPBM. The analysis showed significant increases in IFlow in cortical regions surrounding the stimulation site during the first 4-min and last 3-min tPBM period, when compared to sham. Specifically, at alpha (7-13 Hz) and beta (13-30 Hz) bands, IFlow showed significant increases in the right frontal region near the tPBM site; at delta (0.1-4 Hz) and theta (4-7 Hz) bands, IFlow had significant increases during the first 4-min stimulation; at gamma (30-70 Hz) frequency, IFlow presented significant enhancements during the last 4-min and post stimulation. As for the first time, this study demonstrated that the cortical areas enhanced for their IFlow by right prefrontal tPBM were co-located with the cortical pathways for learning and memory functions, shedding light on mechanistic association of tPBM-evoked cortical electrophysiological connectivity with improvement of human cognition. Aim 3 was to investigate the tPBM-induced effects by different wavelengths, namely, at 1064, 852, and 808 nm for better reviewing and interpreting essential mechanisms of action involved in wavelength-dependent tPBM. Specifically, sham-controlled PBM effects with 1064-, 852-, 808-nm laser were measured from the forearm of 10 healthy adults using bb-NIRS with 2-min baseline, 8-min PBM, and 5-min recovery. After repeated measures ANOVA, compared to the responses under sham, while 1064-nm PBM showed consistent increases of ∆[HbO] and ∆[oxi-CCO], 852-nm PBM resulted in enhancement of ∆[HbO], ∆[HbT] but not ∆[oxi-CCO] and 808-nm PBM caused a delayed increase in only ∆[oxi-CCO]. Indeed, the newly-collected, hemodynamic and metabolic changes induced by PBM at these wavelengths are the first objective report in the field, providing the observation that cannot be well explained by the conventional PBM theory. To interpret the experimental results, accordingly, I proposed or hypothesized three semi-novel pathways by considering both CCO-oxidized and heat-regulated pathways concurrently activated by light. Given the limited number of human subjects, further investigation and validation for this model are needed and will be our future work. Furthermore, it would be very beneficial if there exists a theoretical model that allows us to relate the PBM power or outcome with (1) optical properties of tissue, (2) light penetration depth, (3) power density of light, and (4) aperture size of the light. In Chapter 5, we developed an analytical expression of light fluence as a function of such parameters based on diffusion theory, followed by laboratory validation using liquid tissue phantoms. Specifically, a tank of the 4-liter liquid phantom was made of an intralipid solution and black ink or horse blood. Fluence measurements were taken with variable laser power densities and aperture sizes. The analytical solution of fluence showed excellence to match the experimental observations using different power density and aperture size of the 1064-nm laser. We concluded that an analytical equation was successfully confirmed for its accuracy to predict, estimate or quantify optical fluence within tissue treated by PBM.

Keywords

PBM, Multi-wavelength, information flow

Disciplines

Biomedical Engineering and Bioengineering | Engineering

Comments

Degree granted by The University of Texas at Arlington

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