Assessing Functional Deficits at Optic Neuritis Onset in EAE Mice Using Manganese-Enhanced MRI (MEMRI) and Diffusion fMRI

Optic neuritis (ON) is frequently a first sign of multiple sclerosis (MS), which is an inflammatory demyelinative disease of the central nerve system (CNS), including brain, optic nerve, and spinal cord. Investigating ON provides an approach to improve MS diagnosis and treatment monitoring. Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model of MS and exhibits pathologies similar to the human disease. Magnetic resonance imaging (MRI) is a non-invasive tool to detect disease progress and as a standard diagnose procedure for MS in the clinic. In biological samples, the hydrogen nuclei are used to produce the MR signal due to its abundance in water and fat. As a result of tissue microstructural differences, 1H nuclei exhibit tissue-specific and pathology-specific relaxation and diffusion properties, which are reflected in the resulting MR image contrast. Therefore, the pathologies of MS, such as inflammation, demyelination, and axonal injury can be detected using different MR-related tools, including T1- and T2-weighted imaging, diffusion-weighted imaging, and diffusion tensor imaging, and so on. Importantly, direct non-invasive assessment of functional deficits could be important for understanding pathology mechanisms or provide a useful bio-index to validate treatment strategies. In this dissertation, manganese-enhanced MRI (MEMRI) and diffusion fMRI were introduced to explore the functional deficits, including axonal transport disruption and axon-activity dysfunction, at optic neuritis onset in EAE mice.