Characterizing Susceptibility Weighted MRI in the Experimental Autoimmune Encephalomyelitis Mouse Model of Multiple Sclerosis
Abstract
Susceptibility-based magnetic resonance imaging (MRI) methods have been used in multiple sclerosis (MS) patients for lesion detection, visualization of the venous vasculature and to show abnormal iron accumulation in the deep grey matter structures of the brain. The overarching goal of this thesis was to characterize one of the susceptibility-based MRI methods, susceptibility weighted imaging (SWI), in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. First, we investigated if SWI could detect lesions (or hypointensities) in the lumbar spinal cords and cerebella of EAE mice. We found that SWI hypointensities were present in a region-specific manner in the CNS of EAE mice, where most of these lesions were attributed to deoxyhemoglobin and a smaller number were due to parenchymal iron deposition. Next, we validated a method to identify deoxyhemoglobin-based SWI hypointensities in vivo which entailed combining SWI with hyperoxygenation. Following this, we sought to investigate when SWI hypointensities appear during the EAE disease course and how they change over the course of the disease. This was studied by carrying out serial SWI in vivo in naïve mice and mice immunized for EAE. Here, we found that SWI hypointensities are prominent before signs of motor dysfunction in EAE mice. SWI hypointensities were also observed to evolve over the disease course. Of note, the number of SWI hypointensities was always at a maximum before or at the same time as maximum motor dysfunction. Unlike EAE mice, the number of SWI hypointensities remained stable through all imaging time points in naïve mice, suggesting that SWI hypointensities are linked to EAE pathophysiology. Lastly we used SWI to assess treatment response to an anti-inflammatory treatment (dexamethasone) in EAE mice. This was carried out under the premise that SWI hypointensities may be linked to inflammation, so reducing inflammation could reduce the number of SWI hypointensities present. Our preliminary data suggest that SWI may be able to act as a surrogate marker of inflammation. Overall, findings from this thesis support the use of SWI in future studies in the EAE model to investigate the venous vasculature and parenchymal iron deposition.
Description
Keywords
Neuroscience, Radiology
Citation
Nathoo, N. (2014). Characterizing Susceptibility Weighted MRI in the Experimental Autoimmune Encephalomyelitis Mouse Model of Multiple Sclerosis (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/25303