An unconstrained four pool model analysis of proton relaxation and magnetization transfer in ex vivo white matter

Understanding proton relaxation in the brain's white matter remains an active field of magnetic resonance imaging research. Models of varying complexity have been proposed to link measurements to tissue composition/microstructure, in particular myelination. Although the presence of multiple aqueous and nonaqueous proton pools is well established experimentally, so-called "quantitative MRI" is usually based on simpler models due to the large number of model parameters. In this work, a comprehensive set of parameters characterizing a four-pool model is obtained. A piece of fixed porcine spinal-cord WM was investigated at 3 T and temperatures between 21 and 35 °C. Measurements included a wide range of preparations of the spin system in combination with long echo trains to achieve sensitivity to all model parameters. The results allow the extraction of all intrinsic relaxation and exchange rates as well as assigning them to specific dynamic processes involving tissue water. A critical assessment indicates that simpler models often lack specificity to myelin.