| Summary: | Magnetic resonance imaging (MRI) is unique in its sensitivity to a wide array of contrast mechanisms in soft tissue. Unfortunately, the physiological and/or microanatomical characteristics that give rise to this contrast can show significant heterogeneity on the scale of a typical voxel, resulting in an observed nuclear magnetic resonance (NMR) signal that is a summation of these spatially varying characteristics. Multicomponent analysis, which allows one to separate the observed NMR signal into components that represent underlying sub-voxel tissue compartments, can be used to deal with this limitation. For example, this approach has been applied to myelinated tissue (e.g., white matter, peripheral nerve) to measure the so-called myelin water fraction, which has been shown to correlate with myelin content. Despite this promise, several fundamental issues regarding the compartmental models used to describe myelinated tissue exist. These include: 1) quantifying the effect of intercompartmental exchange and 2) the inability to resolve axonal water (water within myelinated axons) from interaxonal water (water outside myelinated axons) in the central nervous system.
This dissertation presents a series of studies aimed to address these fundamental issues. To address the effect of exchange, a novel method for quantifying exchange rates, which allows for a significant reduction in scan time relative to existing methods, was developed. This method was tested and compared to existing methods via simulations studies, validated via phantom studies, and applied in excised myelinated tissue samples. To investigate methods for resolving axonal and interaxonal water, compartmental relaxation measurements were performed in myelinated tissue samples before and after administration of contrast reagents as a means to characterize the compartmental enhancement pattern associated with each reagent. The results of these studies suggest that administration of potassium dichromate in white matter and optic nerve ex vivo might allow one to resolve axonal and interaxonal water in these tissues. Though not directly related, an additional study was included, which showed that novel information about tumor microenvironment may be available in vivo using the multicomponent analysis techniques presented throughout this work.
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