Influence of cell cycle phase on apparent diffusion coefficient in synchronized cells detected using temporal diffusion spectroscopy

Abstract

The relationship between the apparent diffusion coefficient of tissue water measured by MR methods and the physiological status of cells is of particular relevance for better understanding and interpretation of diffusion-weighted MRI. In addition, there is considerable interest in developing diffusion-dependent imaging methods capable of providing novel information on tissue microstructure, including intracellular changes. To this end, both the conventional pulsed gradient spin-echo methods and the oscillating gradient spin-echo method, which probes diffusion over very short distance (<<cell size) and time scales, were used to measure apparent diffusion coefficient of synchronized packed HL-60 cells at 7 T. The results show that the pulsed gradient spin-echo method with relatively long diffusion times does not detect changes in apparent diffusion coefficient when structural variations arise during cell division. On the contrary, the oscillating gradient spin-echo method can detect and quantify major changes in intracellular organization that occur during mitosis by appropriate choice of gradient frequency. Cell structural parameters, including cell size, intracellular diffusion coefficient, and surface-to-volume ratio were also obtained by fitting the oscillating gradient spin-echo data to simple analytical models. These oscillating gradient spin-echo features may be used in diffusion-weighted MRI to create parametric maps that may be useful for detecting cancer or changes caused by treatment.