White matter intercompartmental water exchange rates determined from detailed modeling of the myelin sheath

PURPOSE: Magnetization exchange (ME) between hydrogen protons of water and large molecules (semisolids [SS]) in lipid bilayers is an important factor in MRI signal generation and can be exploited to study white matter pathology. Current models used to quantify ME in white matter generally consider water to reside in 1 or 2 distinct compartments, ignoring the complexities of the myelin sheath's multicompartment structure of alternating myelin SS and myelin water (MW) layers. Here, we investigated the effect of this by fitting ME data obtained from human brain at 7 T with a multilayer model of myelin. METHODS: A multi-echo acquisition for a T2* -based separation of MW from other water signals was combined with various preparation pulses to change the (relative) state of the SS and water pools and analyzed by fitting with a multilayer exchange model. RESULTS: The estimated lifetime within a single MW layer was 260 µs, corresponding to a lipid bilayer permeability of 6.7 µm/s. The magnetization lifetime of the aggregate of all MW was estimated at 13 ms, shorter than previously reported values in the range of 40 to 140 ms. CONCLUSION: Contrary to expectations and previous reports, ME between protons in myelin SS and water is not limited by the myelin sheath but rather by the exchange between SS and water protons. The analysis of ME contrast should account for the relatively short MW lifetime and affects the interpretation of tissue compartmentalization from MRI contrasts such as T1 - and diffusion-weighting.