Experimental validation of a bias in apparent exchange rate measurements

Double diffusion encoding (DDE) MRI is a technique in which two diffusion weighted periods are applied between excitation and acquisition. This allows to acquire structural information (as pore size and shape) and molecular exchange between compartments, in terms of apparent exchange rate (AXR). However, it has not been well investigated yet whether the diffusion restriction underlying DDE size estimation may compromise AXR results. Numerical simulations for impermeable spheres have shown that in case of small pores (diameter < 10 μm) the restriction effect may be neglected. Yet, for larger pores, the restriction effect can be relevant and needs to be considered in the analysis of experiments. Here, we present experiments performed on a 3 T clinical MRI system using a water-in-oil emulsion in which no exchange between compartments is expected. The results show that a nonzero apparent exchange rate may be estimated in a sample with impermeable pores. This shows that, as predicted in simulations, the restriction effect affects the AXR results. The use of perpendicular diffusion gradients may be a solution for this problem in isotropic samples.