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This document is a critical synopsis of prior work by Michael Dwyer submitted in support of a PhD by published work. The selected work is focused on the application of quantitative magnet resonance imaging (MRI) analysis techniques to the study of multiple sclerosis (MS). MS is a debilitating disease with a multi-factorial pathology, progression, and clinical presentation. Its most salient feature is focal inflammatory lesions, but it also includes significant parenchymal atrophy and microstructural damage. As a powerful tool for in vivo investigation of tissue properties, MRI can provide important clinical and scientific information regarding these various aspects of the disease, but precise, accurate quantitative analysis techniques are needed to detect subtle changes and to cope with the vast amount of data produced in an MRI session. To address this, eight new techniques were developed by Michael Dwyer and his co-workers to better elucidate focal, atrophic, and occult/"invisible" pathology. These included: a method to better evaluate errors in lesion identification; a method to quantify differences in lesion distribution between scanner strengths; a method to measure optic nerve atrophy; a more precise method to quantify tissue-specific atrophy; a method sensitive to dynamic myelin changes; and a method to quantify iron in specific brain structures. Taken together, these new techniques are complementary and improve the ability of clinicians and researchers to reliably assess various key elements of MS pathology in vivo.