Diffusion weighted magnetic resonance imaging by temporal diffusion spectroscopy
Diffusion-weighted magnetic resonance imaging (DWI) provides a unique approach for probing the microstructure of biological tissues and is an important tool for both clinical and research applications, such as for the diagnosis of stroke and detection of cancer. However, conventional DWI measurements using pulsed gradient spin echo (PGSE) methods cannot in practice probe very short diffusion times because of hardware limitations, and this restriction prevents conventional DWI from being able to characterize changes in intra-cellular structure, which may be critical in many applications. The method of diffusion temporal spectroscopy using oscillating gradient spin echo (OGSE) methods has been proposed to probe short diffusion times and to provide additional contrast in diffusion imaging. A comprehensive study of diffusion temporal spectroscopy is presented in this thesis, including (1) a simulation of OGSE methods in cellular systems using an improved finite difference method for more accurate and efficient computation of results ; (2) studies of biological tissues and DWI signals with diffusion temporal spectroscopy in order to predict and interpret data and extract quantitative tissue microstructural information; and (3) demonstration of the increased sensitivity of DWI measurements to variations of intracellular structures, such as nuclear sizes, using the diffusion temporal spectroscopy method. The work presented here provides a framework to interpret DWI data to obtain biological tissue microstructural information and may enhance the ability of diffusion imaging to be used as a biomarker for, for example, assessing the state of tumors in pre-clinical research.