Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Medical Biophysics

Supervisor

Dr. Keith St. Lawrence

Abstract

The Blood-brain barrier (BBB) regulates the entry of compounds between the blood and the brain, thus plays an important role in brain homeostasis. Studies indicate in disease states such as Alzheimer’s the BBB integrity is compromised. The motive of this project is to investigate the sensitivity of the diffusion-weighted arterial spin labeling (DW-ASL) technique to detect water exchange. Testing the sensitivity requires a reliable method of opening the barrier at specific locations of the brain. Here, a unique technology named focused ultrasound (FUS) has been used to mimic a compromised BBB environment.

A series of experiments were conducted in a piglet model to determine the ideal settings for a successful BBB opening. The combination of 2.5 W of power, 0.02 ml/kg of microbubble concentration while saturated O2 levels in the piglet were controlled revealed the most effective BBB opening without causing hemorrhage. Although the study was able to show a significant BBB opening in contrast-enhanced MRI, the DW-ASL images showed no significant difference between the sonicated and non-sonicated ROIs. However, the average water exchange rate (kw) of 106 min-1 measured in this study corresponds to a permeability surface area product (PSw) of 159 ml/100 g/min, which was comparable to the measurements in the prior study involving humans.

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