White matter inter-compartmental water exchange rates determined from detailed modeling of the myelin sheath

Abstract

Purpose

Magnetization exchange (ME) between hydrogen protons of water and large molecules (semisolids) 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 one or two distinct compartments, ignoring the complexities of the myelin sheath’s multi-compartment structure of alternating myelin semisolids and myelin water layers. Here, we investigated the effect of this by fitting ME data obtained from human brain at 7 T with a multi-layer model of myelin.

Methods

A multi-echo acquisition, for a T ₂ ^* based separation of myelin water from other water signals, combined with various preparation pulses to change the (relative) state of the semisolid and water pools, analyzed by fitting with a multi-layer exchange model.

Results

The estimated lifetime within a single myelin water layer was 260 μs, corresponding to a lipid bilayer permeability of 6.7 μm/s. The magnetization lifetime of the aggregate of all myelin water was estimated at 13 ms, shorter than previously reported values in the range of 40–140 ms.

Conclusion

Contrary to expectations and previous reports, ME between protons in myelin semisolids and water is not limited by the myelin sheath, but rather by exchange between semisolids and water protons. The relatively short myelin water lifetime should be accounted for in the analysis of ME contrast, and affects the interpretation of tissue compartmentalization from MRI contrasts such as T ₁- and diffusion-weighting.