Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

Baron, Corey

2nd Supervisor

Menon, Ravi

Co-Supervisor

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.

Summary for Lay Audience

Medical imaging gives us the ability to noninvasively view tissues and organs within the body. It plays a critical role in the detection and diagnosis of diseases and injuries, lets us monitor progression or recovery, and even allows for prenatal screening. There are many different medical imaging modalities, and each has its own specific strengths and weaknesses.

Diffusion magnetic resonance imaging (dMRI) is a specialized imaging technique that is sensitive to the motion of water molecules in tissue, which is affected by interactions with obstacles such as membranes and macromolecules. dMRI takes advantage of the relationship between water diffusion and tissue properties to reveal details about tissue architecture on a microscopic level. Microscopic fractional anisotropy (µFA) is a dMRI metric that quantifies the asymmetry of water diffusivity across different directions. For example, consider a typical neuron which has a long axon projecting from its cell body. Intracellular diffusivity is greater along the axon’s length than in the directions perpendicular to it because of restricting membranes; thus, diffusion in the neuron is highly anisotropic. Disease or injury can alter the neuron’s shape and properties, reducing anisotropy, and thus µFA may potentially serve as a surrogate biomarker of injury or disease in neuroimaging.

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, and Chapter 3 focuses on a modification to the technique that may improve its specificity to disease or injury in regions of the brain that are adjacent to cerebrospinal fluid-containing ventricles. The work described in Chapter 4 explores the sensitivity of µFA to hippocampal abnormalities in patients with temporal lobe epilepsy. Finally, Chapter 5 summarizes the contributions of this Thesis and provides suggestions for future studies.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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