Microstructure estimation from diffusion-MRI: Compartmentalized models in permeable cellular tissue

Diffusion-weighted magnetic resonance imaging (DW-MRI) is used to characterize brain tissue microstructure employing tissue-specific biophysical models. A current limitation, however, is that most of the proposed models are based on the assumption of negligible water exchange between the intra- and extracellular compartments, which might not be valid in various brain tissues, including unmyelinated axons, gray matter, and tumors. The purpose of this work is to quantify the effect of membrane permeability on the estimates of two popular models neglecting exchange, and compare their performance with a model including exchange. To this aim, DW-MRI experiments were performed in controlled environments with Monte-Carlo simulations. The DW-MRI signals were generated in numerical substrates mimicking biological tissue made of spherical cells with permeable membranes like cancerous tissue or the brain gray matter. From these signals, the substrates properties were estimated using SANDI and VERDICT, the two compartment-based models neglecting exchange, and CEXI, a new model which includes exchange. Our results show that, in cellular permeable tissue, the model with exchange outperformed models without exchange in the estimation of the tissue properties by providing more stable estimates of cell size, intracellular volume fraction and extracellular diffusion coefficient. Moreover, the model with exchange estimated accurately the exchange time in the range of permeability reported for cellular tissue. Finally, the simulations performed in this work showed that the exchange between the intracellular and the extracellular space cannot be neglected in permeable tissue with a conventional PGSE sequence, to obtain accurate estimates. Consequently, existing compartmentalized models of impermeable tissue cannot be used for microstructure estimation of cellular permeable tissue.