Biophysical modelling in diffusion MRI: The role of tissue microstructure and water exchange

Abstract: Diffusion MRI is widely used to study brain structure in vivo. While this technique is often applied to investigations of brain connectivity, it can also be used to infer specific information about the tissue microstructure; for example, to estimate the axon diameter. In the present work, the role of tissue microstructure and water exchange in biophysical models employed in diffusion MRI was investigated. Specialised diffusion measurements were performed in white matter of healthy volunteers and in subacute stroke lesions. The results showed that exchange between microenvironments with different diffusivities contributes to the outcome of the diffusion MRI experiment. Concerns regarding the accuracy and precision of model-parameter estimates were addressed by using Monte Carlo simulations of the diffusion MRI experiment. The results showed that axon diameters can be accurately estimated above the resolution limit of the experiment. The fraction of water restricted to the axons, however, became underestimated at high exchange rates, although a remedy for this problem was suggested. Additional simulations showed the importance of modelling the three-dimensional structural properties of nerves containing undulating axons. Neglecting the presence of such undulations could result in overestimation of axon diameters. Stretching or compression of tissue comprising undulating axons may result in alterations of the diffusivity possible to detect by diffusion MRI. The filtered exchange imaging (FEXI) method was developed in order to improve the sensitivity of diffusion MRI to diffusional water exchange. Measurements on yeast cell suspensions using NMR spectrometers and a clinical MRI scanner were used to validate the method. FEXI was successfully applied to determine the water exchange rate in the healthy human brain and in a brain tumour, showing that systematic investigation of the water exchange rate in vivo is possible. In conclusion, this work improved the feasibility of using clinical MRI scanners to investigate tissue microstructure and the rate of water exchange.