Development and applications of data analysis tools for multimodal positron emission tomography and magnetic resonance imaging sytems

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Date
2021-06
Authors
Perron, Jarrad
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Abstract
Two experiments (𝑁 = 5, 𝑁 = 2) were performed at the Magnetic Resonance Microscopy Centre (MRMC) in Winnipeg (MB) in an attempt to use simultaneous positron emission tomography and magnetic resonance (PET-MR) imaging to demonstrate the in vivo selective activation of serotonergic 5-HT neurons in rats. These experiments take advantage of a new imaging system developed by Cubresa Inc (Winnipeg, MB) called ‘NuPET’. This device is an MR-compatible PET insert which is placed around the subject while they are within the bore of a MR device. That allows simultaneous PET-MR imaging. To activate 5-HT neurons selectively we use designer receptors exclusively active by designer drug (DREADD) technology. These DREADDs are designer G-protein-coupled receptors. Neurons at the site of a stereotactic injection are transfected with a viral vector containing the proteins necessary to force expression of DREADDs in genetically modified rats. These may then be activated by administering the drug clozapine-N-oxide (CNO). This technique allows for precise spatiotemporal control of receptor signaling. The MRMC is highly experienced in MR experiments, but had no in-house capability to analyze the data gathered during PET-MR studies. This thesis presents the development and application of a custom-designed workflow and collection of Matlab scripts which organizes and streamlines the tasks associated with PET-MR post-processing and analysis. This is intended as a tool that may be used for any future PET-MR experiments at the MRMC, and be continually expanded as the needs of the lab grow more sophisticated. In the application of the Slapdash workflow, it was determined that we cannot confirm that the experiments were able to image the in vivo activation of serotonergic neurons. Statistical analysis performed with paired-sample t-testing reveals statistically significant differences in activity between initial and subsequent PET frames throughout both experiments, but numerous methodological issues mar our ability to draw any meaningful conclusions from the data.
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multimodal, PET, MRI, analysis, postprocessing, hybrid, animal, rodent, Slapdash
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