Xinlong Wang

Graduation Semester and Year




Document Type


Degree Name

Doctor of Philosophy in Biomedical Engineering



First Advisor

Hanli Liu


Photobiomodulation (PBM) refers to the use of red-to-near-infrared light to stimulate cellular functions for physiological or clinical benefits. Transcranial photobiomodulation (tPBM) is a noninvasive form of cerebral photobiomodulation that has been observed with various improvements in human cognitive functions. The mechanism of tPBM is assumed to rely on photon absorption by cytochrome c oxidase (CCO), the terminal enzyme in the mitochondrial respiratory chain that catalyzes the reduction of oxygen for energy metabolism. However, few studies have objectively investigated hemodynamic, metabolic and electrophysiological response of the human brain to tPBM. To address this gap, my dissertation research has focused on objective measures of metabolic, hemodynamic, and electrophysiological effects of tPBM on the human brain, for the first time, by implementing broadband near infrared spectroscopy (bb-NIRS) hardware, designing novel methodology and experiments, developing new data analysis algorithms, and validating the overall development with computer simulations. Specifically, my dissertation in Chap. 2 validated the bb-NIRS methodology and demonstrated the interplay between increases in [CCO] and hemoglobin concentrations for the first time during PBM, indicating that a hemodynamic response of oxygen supply and blood volume closely coupled to the up-regulation of CCO induced by PBM. In Chap. 3, my research work further confirmed that tPBM can (1) significantly increase cerebral concentrations of oxidized CCO ([CCO]; >0.08 M; p<0.01), oxygenated hemoglobin ([HbO]; >0.8 M; p<0.01), and total hemoglobin ([HbT]; >0.5 M; p<0.01) during and after the laser stimulation, and (2) also introduce a linear interplay between [CCO] versus [HbO] and between [CCO] versus [HbT]. This study provided the first demonstration that tPBM causes up-regulation of oxidized CCO in the human brain, and contributes important insight into the physiological mechanisms. To discriminate thermal confounding effects of tPBM on the above results, I with my research colleagues conducted human thermal experiments and confirmed, as reported in Chap. 4, that heat-based stimulation would give rise to [CCO] and [HbO] changes opposite to those by tPBM. Furthermore, in Chap 5 I reported a novel algorithm/methodology to quantify absolute concentrations of cytochrome c oxidase (CCO) and other tissue components including oxygenated hemoglobin (HbO), deoxygenated hemoglobin (HHb), water fraction (water%), fat fraction (fat%) and reduced light scattering coefficient by utilizing an Ant colony optimization model. The algorithm utilized characteristic spectral features of the 1st and 2nd derivatives of wavelength-dependent extinction coefficients based on Diffusion Approximation. Computational simulation was performed to verify proper estimation accuracy. Finally, in Chap. 6, I explored the electrophysiological effect of tPBM by collecting 64-channel electroencephalogram (EEG) from each human subject’ head during and after tPBM in a placebo-controlled experiment. Dose-dependent increases of EEG power were observed during and after tPBM at five frequency bands. An EEG source-reconstruction algorithm and the Phase Transfer Entropy (PTE) analysis were used to analyze tPBM-induced changes in neural electrophysiology. The results demonstrated strong enhancement of cerebral information flow from selected regions and potential benefit of tPBM to human global cerebral activation and cognitive functions.


Photobiomodulation, NIRS, Cytochrome c oxidase, Broadband spectroscopy, EEG, Hemoglobin


Biomedical Engineering and Bioengineering | Engineering


Degree granted by The University of Texas at Arlington