Graduation Year

2022

Document Type

Dissertation

Degree

Ph.D.

Degree Name

Doctor of Philosophy (Ph.D.)

Degree Granting Department

Biomedical Engineering

Major Professor

Huabei Jiang, Ph.D.

Committee Member

Robert Frisina Jr., Ph.D.

Committee Member

william Lee III, Ph.D.

Committee Member

George Spirou, Ph.D.

Committee Member

Brendan Walker, Ph.D.

Keywords

Chronic Alcoholism, Binge Drinking, Low Intensity Focused Ultrasound, High Alcohol-Preferring Mice, Neuromodulation

Abstract

This research has two parts. The first part focuses on the use of photoacoustic imaging (PAI) to study alcohol-induced effects in the cerebral vasculature of selectively bred alcohol-preferring mice. Part two extends the application of PAI by developing a novel Photoacoustic imaging guided system for repetitive low intensity focused ultrasound (PAI-LIFU) stimulation treatment for alcohol use disorder in crossed high alcohol preferring (cHAP) mice.

Photoacoustic imaging is an emerging hybrid non-invasive optical imaging modality which relies on optical absorption contrast to visualize deep tissue structures and function. It combines the high contrast associated with pure optical imaging and the high resolution associated with pure ultrasonic imaging, to visualize three dimensional tissues structures, vascular morphology as well as provide functional information with high spatial resolution and excellent contrast.

We exploit the significant difference in optical absorption between hemoglobin, deoxyhemoglobin and the surrounding tissues to image and study the direct effects of ethanol on the cerebrovascular system in selectively bred alcohol preferring mice. Alcohol induced effects, including changes in vascular diameter and cerebrovascular perfusion are studied for two alcohol drinking paradigms namely: - binge and chronic alcohol use. In a functional imaging approach, we study physiological changes and functional activities notably alcohol-induced hemoglobin oxygen saturation for both drinking paradigms. The results from this study show that both chronic and binge alcohol use are associated with cerebral vascular constriction, as observed in the alcohol-preferring mice. More importantly, we have shown that the constriction in cerebral blood vessels and the drop in hemoglobin oxygen saturation following binge drinking is more drastic in occasional binge drinkers, compared to habitual binge drinkers or individuals with alcohol use disorder.

We developed a novel Photoacoustic imaging guided system for repetitive low intensity focused ultrasound stimulation (PAI-LIFU) for the treatment of alcohol use disorder in crossed high alcohol-preferring (cHAP) mice. Results from the treatments using our system suggest that LIFU, targeted to the nucleus accumbens (NAc) in the brain of cHAP mice, reduces ethanol consumption with a marked increase in water consumption in a two-bottled choice paradigm. Furthermore, by analyzing the ratio of the volume of ethanol consumed to the total volume of fluid consumed, we note a significant drop in ethanol preference ratios in favor of water, following LIFU stimulation of the NAc.

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