Time-Dependent Diffusion in the Body

Abstract

Hardware and physiology impose stringent constraints on the millimeter-scale resolution limits of Magnetic Resonance Imaging (MRI). Diffusion MRI is a technique that can effectively surpass the resolution limit by deriving contrast from micrometer restrictions to water diffusion. This thesis studies time dependence of the diffusion coefficient, D(t), in the body [muscle and prostate], where the specificity towards tissue microanatomy is unlocked through biophysical modeling. Unlike the brain, muscle and prostate have a broad range of length scales facilitating the measurement of a dynamic range of D(t). Chapter 1 introduces the physical description of the MRI signal and D(t). Chapter 2 considers the practical/engineering considerations of measuring D(t) on MRI systems. Chapter 3 demonstrates the measurement of temporal diffusion limits on a fiber phantom. Chapter 4 measures and models D(t) in muscle tissue, revealing the myofiber diameter, which is a biomarker shown to be sensitive towards both atrophy and hypertrophy. Chapter 5 measures and models D(t) in prostate cancer, thus revealing stromal cell and luminal diameters. Furthermore, evidence is provided that considerations of D(t) allows for the separation of various prostate cancer grades using MRI. Chapter 6 reviews the findings of this thesis and considers the potential clinical implications from this work