Surface-to-Volume Ratio Mapping of Tumor Microstructure Using Oscillating Gradient Diffusion Weighted Imaging

Purpose: To disentangle the free diffusivity (D-0) and cellular membrane restrictions, by means of their surface-to-volume ratio (S/V), using the frequency-dependence of the diffusion coefficient D(omega), measured in brain tumors in the short diffusion-time regime using oscillating gradients (OGSE). Methods: In vivo and ex vivo OGSE experiments were performed on mice bearing the GL261 murine glioma model (n = 10) to identify the relevant time/frequency (t/omega) domain where D(omega) linearly decreases with omega(-1/2). Parametric maps (S/V, D-0) are compared with conventional DWI metrics. The impact of frequency range and temperature (20 degrees C versus 37 degrees C) on S/V and D-0 is investigated ex vivo. Results: The validity of the short diffusion-time regime is demonstrated in vivo and ex vivo. Ex vivo measurements confirm that the purely geometric restrictions embodied in S/V are independent from temperature and frequency range, while the temperature dependence of the free diffusivity D-0 is similar to that of pure water. Conclusion: Our results suggest that D(omega) in the short diffusion-time regime can be used to uncouple the purely geometric restriction effect, such as S/V, from the intrinsic medium diffusivity properties, and provides a nonempirical and objective way to interpret frequency/time-dependent diffusion changes in tumors in terms of objective biophysical tissue parameters. (C) 2015 Wiley Periodicals, Inc.