Evaluating the utility of advanced MRI methods for monitoring structural changes in demyelinated lesions using two models of multiple sclerosis
Date
2019-07-30
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Abstract
The ability to precisely evaluate tissue pathologies and their functional correlates has been an ongoing challenge in patients with multiple sclerosis (MS). MS pathology is complex; however, much of them start from or are mediated by a demyelinating event. In this thesis, I have studied 2 common models of MS: a cuprizone mouse model, and an optic neuritis (ON) human model. I have particularly focused on the investigation of the potential of novel advanced magnetic resonance imaging (MRI) techniques including neurite orientation dispersion and density imaging (NODDI), diffusion tensor imaging (DTI), and MRI texture analysis. The first model evaluates the ability of these methods to assess the time course and regional preference of MS-like pathology following induced demyelination and spontaneous remyelination in mouse brain. The second model tests the feasibility of select imaging measures for detecting structural changes in the optic nerves and correlating clinical measures in acute optic neuritis (AON) as part of a clinical trial of high dose vitamin D. Through a focused study of the corpus callosum over an extended time series, the animal study shows that all MRI metrics have detected the expected changes over the de- and remyelination periods, consistent with histology quantified using a texture method, structure tensor analysis. The NODDI metric neurite density index is specific to myelin integrity, NODDI orientation dispersion index to axonal changes, and texture angular entropy specific to both myelin and axonal changes. Moreover, early de- and remyelination seems to occur in the genu of corpus callosum featuring relatively thin and high-density axons and early demyelination but relatively late repair in the splenium showing large calibre and comparably low-density axons. All NODDI metrics appear to outperform DTI metrics. In a clinical setting, the advanced imaging measures have successfully detected the structural changes in the affected versus non-affected optic nerves and angular entropy correlates with patient disability. Collectively, this thesis suggests that advanced MRI measures are powerful indices of MS-like pathology and could be used clinically for monitoring disease development and treatment responses, deserving further validation.
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MRI, Neuroscience, Neuroprotection, multiple sclerosis, optic neuritis, texture analysis, NODDI
Citation
Hossain, M. S. (2019). Evaluating the utility of advanced MRI methods for monitoring structural changes in demyelinated lesions using two models of multiple sclerosis (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.