Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Master of Science

Program

Medical Biophysics

Supervisor

Hicks Justin

2nd Supervisor

Anazodo Udunna

Co-Supervisor

Abstract

Alteration in the blood-brain barrier integrity represents an early pathological process in Alzheimer’s disease, and neuroimaging tools, especially magnetic resonance imaging (MRI) and positron emission tomography (PET) are important for blood-brain barrier (BBB) integrity assessment. Unfortunately, these tools are not universally accessible. We first reviewed the literature on the use of these neuroimaging tools in dementia research to provide a global dementia imaging landscape with a focus on Sub-Saharan Africa and a perspective on the dementia resources needed to conduct comparable research in these populations. This revealed that MRI density per million population outweighs PET, but MRI may not adequately visualize BBB integrity. While there are emerging MRI techniques for BBB imaging, the sensitivity of these techniques for early detection is unclear. Thus, validating more available MRI with PET gold standards of [15O]water and [11C]butanol reduces the challenges associated with dementia neuroimaging. To enable PET validation studies, we have developed a robust, automated radiosynthesis of [11C]butanol which is free from confounding ethanol in the final injection on a widely available synthesizer. Preliminary imaging studies with the synthesized [11C]butanol via a hybrid PET/MR are reported.

Summary for Lay Audience

Alzheimer’s disease, the most common cause of dementia, is a brain disorder that affects memory and behavior. Studies have shown that Alzheimer’s disease begins damaging the brain up to two decades before the symptoms occur. The breakdown of the blood-brain barrier has been identified as one of the earliest processes that initiate damage to the brain. The blood-brain barrier is a protective network surrounding the brain and prevents the entry of potentially toxic materials into the brain. This means if we can detect its breakdown in time, there is hope of delaying the symptoms in the future. Medical imaging, particularly magnetic resonance imaging (MRI) and positron emission tomography (PET) are helpful tools to better understand Alzheimer’s disease. MRI takes advantage of the fact that the human body is about 70% water, and it uses this water, with the help of a magnet, to understand how water behaves in the brain. PET, on the other hand, is a technology that involves the injection of radiopharmaceuticals. These emit a small amount of radiation so we can visualize processes that occur within the body using an external camera. Unfortunately, these tools are not universally available and are limited to high-resource centres. We reviewed the literature discussing MRI and PET studies of dementia to provide a perspective on their global usage with a focus on resource-limited regions such as Sub-Saharan Africa. This confirmed limited MRI/PET use in these regions. Also, we discovered that the MRI availability outweighs PET in these regions. Blood-brain barrier breakdown can be visualized and assessed with PET using techniques developed in the 1980s with two unique radiotracers. These radiotracers can be made using automated synthesizers which are commercially available. However, it is difficult to make one of these radiotracers in the commercially available synthesizer using the currently available method. As there is more MRI available compared to PET, we hope to validate an MRI technique with PET, reducing the barrier to accessibility. A step towards this effort is to optimize the production of one of these radiotracers on a commercially available synthesizer to ensure global usability, increasing the tools available for the study of BBB and dementia at large.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Download

Available for download on Monday, March 31, 2025

Share

COinS