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. The manner in which ADC disperses with gradient frequency (or diffusion time) provides information on the characteristic dimensions of structures within the medium. For example, the dispersion of ADC with oscillating gradient frequency (ΔfADC) has been shown to correlate with axon sizes in white matter and provide novel tissue contrast in images of mouse hippocampus and cerebellum. In this study, the relation between ADC spectra and restricting dimensions are further elucidated and used to derive novel image contrast related to the sizes of intrinsic microstructures. Introduction Diffusion MRI provides a non-invasive means to characterize tissue microstructure, and has been widely used to detect stroke and monitor tumor response to therapy (35-38). The apparent diffusion coefficients (ADCs) measured at different diffusion times are believed to reflect the structural hindrances and restrictions to free water movement at varying length scales (18). Conventional pulsed gradient spin echo (PGSE) measurements of ADC in biological tissues usually involve relatively long diffusion times (20-40 ms), so the corresponding one-dimensional root mean square displacements (RMSDs) of diffusion molecules are on the order of 10 μm. The ADC measured with PGSE is thus observed to correlate with cellularity in several types of tumors (36,39,40). Oscillating gradient spin echo (OGSE) methods have been proposed in order to achieve much shorter diffusion times and hence they are able to differentiate smaller structures with higher sensitivity (20,41). For example, the measured ADCs at high