Towards Clinical Microscopic Fractional Anisotropy Imaging
Abstract
Microscopic fractional anisotropy (µFA) is a diffusion-weighted magnetic resonance imaging (dMRI) metric that is sensitive to neuron microstructural features without being confounded by the orientation dispersion of axons and dendrites. µFA may potentially act as a surrogate biomarker for neurodegeneration, demyelination, and other pathological changes to neuron microstructure with greater specificity than other dMRI techniques that are sensitive to orientation dispersion, such as diffusion tensor imaging. As with many advanced imaging techniques, µFA is primarily used in research studies and has not seen use in clinical settings.
The primary goal of this Thesis was to assess the clinical viability of µFA by developing a rapid protocol for full brain µFA imaging and then applying it to the study of a neurological disease. Chapter 1 presents the motivation behind this Thesis and a detailed summary of general background information that supports the subsequent chapters. Chapter 2 focuses on the development and optimization of a µFA imaging protocol that involves the acquisition of dMRI data in two encoding schemes, linear tensor encoding and spherical tensor encoding, and then a joint fit of the data to the powder kurtosis signal representation. The technique was shown to have good repeat measurement reliability in white matter and measured values strongly correlated with another µFA computed using the gamma signal representation. In Chapter 3, a modified signal representation was investigated to estimate µFA and other indices while mitigating contaminating partial volume effects from free water, such as the cerebrospinal fluid in ventricles. The work described in Chapter 4 explores the sensitivity of µFA to hippocampal abnormalities in patients with unilateral temporal lobe epilepsy. Chapter 5 summarizes the contributions of this Thesis and provides suggestions for future studies.