Magnetization Transfer
Olivier M. Girard1
1Aix-Marseille Univ, CNRS, CRMBM, Marseille, France

Synopsis

This lecture will cover the basic principles of magnetization transfer (MT) imaging techniques targeted toward immobile macromolecules in brain and describe how these techniques may inform on the local tissue microstructure. Following this lecture, the attendees should 1/ understand the origin of the magnetization transfer signal within heterogeneous systems such as brain tissues, 2/ understand simplified biophysical modelling aiming at describing myelinated white matter in the context of MT imaging; and 3/ understand how the orientation of the myelinated axons may affect MT measurements and how this may influence other contrasts (T1, T2) measured in the brain.

Target audience

MRI scientists and engineers interested in brain microstructure and Magnetization Transfer techniques. Clinicians interested in advanced myelin imaging techniques.

Summary of the presentation

Magnetization Transfer (MT) refers to a relatively broad range of MRI experiments allowing to image specific molecules in vivo using MRI. MT relies on indirect detection, by measuring the magnetization of the detectable free water proton pool (with relatively long T2) and relying on transfer of magnetization between the molecules of interest and the free water. In this lecture we refer to MT as targeted to immobile macromolecules; the latter being defined by their broad resonance lines which are associated with motion restricted molecules (long motional correlation time) as well as ultra-short transverse relaxation time (T2 in the range of tens of µs) and are often referred to as the semisolid and/or bound proton pool. According to this definition it is generally non-trivial to get a simple and intuitive mental picture of the involved compounds, since macromolecules are not defined according to their intrinsic size (e.g. expressed in atomic mass units) but rather by their molecular mobility which depends on external factors such as the viscosity of the local environment and the overall tissue architecture at the microscopic (e.g. atomic scale) and the mesoscopic (e.g. cellular scale) scales. Within the scope of brain applications, it has been shown over the years that MT imaging is particularly sensitive to the myelin sheath, which is a large supra-molecular assembly made from the oligodendrocyte cell membrane and containing large amount of lipid chains arranged in a liquid crystalline phase. More recently a refinement of MT, namely the inhomogeneous MT (ihMT), has demonstrated an improved signal specificity toward myelin due to its unique sensitivity to dipolar order and its associated relaxation time (T1D) which is particularly long in the liquid-crystal phase.

Hence it is not surprising that MT MRI has emerged as a mean to assess the tissue microstructure, especially for brain. That being said, it remains challenging to extract tissue information that may be directly interpreted in terms of relevant parameters defining the tissue microstructure (such as the absolute macromolecular content or the averaged size, diameter, or the orientation of the myelin sheath or axons). However, from a wider perspective, one could define the field of MRI microstructure as methods enabling access to information which characterize the tissue at the sub-voxel (i.e micro to mesoscopic) scale. This requires biophysical modeling of the tissue as well as MR physics modelling of the MRI signal, such that one could infer the biophysical parameters from the measured signal. According to this general definition, quantitative MT (qMT) approaches may thus be considered as microstructural modalities. qMT provides access to several parameters of interest such as the relative macromolecular concentration (as expressed by the relative size of the macromolecular proton pool magnetization, normalized by the fee water pool magnetization), the width of the macromolecular lineshape (inversely proportional to the macromolecular T2) or the exchange rate of magnetization between the proton pools. Although these parameters pertain to a simplified biophysical model, that typically aggregates all water proton in a single pool, and similarly for all macromolecules, such quantitative parameters may inform on the local physio-pathological processes. More advanced modelling of the white matter and the myelin sheath and associated exchange processes have also been developed and may provide a refined understanding of the exchange processes, and on the influence of MT mechanisms on relaxation data.

The following lecture will cover the basics principles of MT and associated biophysical modelling enabling measurement of the tissue macromolecular content. In addition, more advanced modelling dedicated to white matter will be covered.

Acknowledgements

I thank my colleagues, collaborators, and all other researchers with whom I have had highly stimulating and helpful scientific discussions about MT and brain microstructure.

References

Useful journal references (non-exhaustive):

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Useful textbooks:

  1. Goldman M. Spin Temperature and Nuclear Magnetic Resonance in Solids. International Series of Monographs on Physics, Clarendon Press, Oxford, 1970.
  2. Slichter CP. Principles of Magnetic Resonance, 3rd Edition. Springer, 1990.
  3. Levitt MH. Spin Dynamics: Basics of Nuclear Magnetic Resonance, 2nd Edition. Wiley, 2008.
Proc. Intl. Soc. Mag. Reson. Med. 29 (2021)