Investigating the magnetic susceptibility contributions of hypoxia and myelin in the mouse brain using quantitative MRI

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dc.contributor.advisorDunn, Jeff
dc.contributor.authorMakarowski, Ty
dc.contributor.committeememberPike, Bruce
dc.contributor.committeememberCamara-Lemarroy, Carlos
dc.date2025-06-03
dc.date.accessioned2025-02-05T23:26:13Z
dc.date.available2025-02-05T23:26:13Z
dc.date.issued2025-01-31
dc.description.abstractMultiple sclerosis (MS) is a chronic autoimmune disease characterized by demyelination and neurodegeneration, with emerging evidence suggesting a critical role of brain hypoxia in its progression. While demyelination has been well-studied, the relationship between hypoxia and myelin loss, and how these processes contribute to disease progression, remains poorly understood. This study evaluates the efficacy of quantitative MRI metrics, specifically R2* and quantitative susceptibility mapping, in detecting and differentiating hypoxia and Cuprizone-induced demyelination in the mouse brain. Using a graded hypoxia model (10% vs. 30% oxygen) and Cuprizone treatment, we acquired R2* and QSM data across the mouse brain. An advanced MRI processing pipeline enabled precise detection of regional changes. R2* was highly sensitive to hypoxia, with significant increases observed throughout the brain that correlated with elevated deoxyhemoglobin levels, highlighting R2* as a promising marker for brain oxygenation. Magnetic susceptibility changes were primarily localized to venous structures, underscoring its spatial specificity to paramagnetic compounds. For Cuprizone-induced demyelination, R2* showed a notable decrease in the corpus callosum, suggesting a homogenization effect due to myelin loss, while QSM detected no significant changes, possibly due to a lack of iron accumulation typically seen in demyelinated lesions in human studies. Comparative analyses indicated that R2* responses were more pronounced in hypoxic than demyelinated states, supporting its sensitivity to magnetic inhomogeneities related to deoxyhemoglobin. These findings suggest that R2* and QSM offer complementary insights into hypoxic and demyelinating processes, with potential for enhancing non-invasive imaging in clinical conditions like multiple sclerosis.
dc.identifier.citationMakarowski, T. (2025). Investigating the magnetic susceptibility contributions of hypoxia and myelin in the mouse brain using quantitative MRI (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.urihttps://hdl.handle.net/1880/120718
dc.language.isoen
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgary
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subjectMRI
dc.subjectmagnetic susceptibility
dc.subjecthypoxia
dc.subjectMultiple sclerosis
dc.subject.classificationRadiology
dc.subject.classificationNeuroscience
dc.titleInvestigating the magnetic susceptibility contributions of hypoxia and myelin in the mouse brain using quantitative MRI
dc.typemaster thesis
thesis.degree.disciplineMedicine – Neuroscience
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
ucalgary.thesis.accesssetbystudentI do not require a thesis withhold – my thesis will have open access and can be viewed and downloaded publicly as soon as possible.
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