| To date, reliable imaging biomarkers to better understand the pathology and progress of Multiple Sclerosis (MS) are lacking. Optic Neuritis (ON), the inflammation of the optic nerve, is commonly associated with MS and provides a system model to develop such biomarkers. In this thesis, I investigate ON and its recovery using diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (fMRI). To date, fMRI studies of ON have not been able to determine if the restoration of visual cortex activity over repeated sessions is the result of cortical plasticity associated with recovery or is merely the response to the restoration of visual input to the cortex from the recovering optic nerve. Resting-state fMRI, on the other hand, investigates the synchrony of brain activity between spatially distinct regions of the brain while the subject is at rest. Performing resting-state fMRI with the eyes closed may potentially remove the confounding effect of reduced visual input from the affected eye. In this thesis, I demonstrate the DTI measurements that differentiate the affected eye from a healthy eye, as well as measurements that are associated with recovery and with clinical measures of visual function. I also demonstrate how resting-state fMRI differentiates ON patients from control subjects, and how resting-state connections are associated with recovery and visual function. These studies potentially identify reliable biomarkers for the study of pathology in MS. In addition, I present a new analysis algorithm for resting-state studies that addresses several problems associated with current techniques. This algorithm is based on the calculation of a correlation transfer function, which determines the relationship between fMRI signals originating from distinct brain regions in terms of the propagation of information throughout the network of brain regions associated with vision. |
