Towards quantitative measurements of tissue microstructure using temporal diffusion spectroscopy
Diffusion MRI provides a non-invasive means to characterize tissue microstructure at varying length scales. Apparent diffusion coefficients (ADCs) of tissue water may be measured at relatively long diffusion times with conventional pulsed gradient spin echo (PGSE) methods, or at much shorter effective diffusion times using oscillating gradient spin echo (OGSE) methods. Besides the information provided by single ADC measurements, the manner in which ADC disperses with gradient frequency (or diffusion time) provides information on the characteristic dimensions of structures within the medium. However, despite increasing interest in applying frequency-dependent ADC to derive novel information on tissue, the interpretations of ADC spectra are not always clear. Meanwhile, to better characterize the tissue microstructure, the direct quantitation of restricting dimensions may be more helpful. The contrast and structural information provided by temporal diffusion spectroscopy are comprehensively studied in this thesis, including (1) the structural information revealed by the dispersion of ADC with frequency; (2) the influence of cell membrane permeability on MR diffusion measurements; and (3) the quantification of restricting size in simple one-pool and two-pool models. This work may help better understand the contrast by temporal diffusion spectroscopy and demonstrates its potential for quantitative measurements of tissue microstructure.