MT and ihMT: basic principles and applications
1Aix Marseille Univ, CNRS, CRMBM, Marseille, France
Synopsis
Keywords: Contrast mechanisms: CEST & MT, Contrast mechanisms: Relaxometry, Contrast mechanisms: Microstructure
This course will cover the basic principles of MT and ihMT and will describe the associated biophysical modelling used to measure tissue macromolecular content using MRI. Following this lecture, the attendees should 1/ understand the origin of magnetization transfer effects within heterogeneous spin systems, 2/ understand that MT mechanisms and T1 longitudinal relaxation are tightly related, 3/ gain intuition on biophysical models aiming to describe MT and ihMT effects, especially in central nervous system tissues, and 4/ know the usual MT and ihMT acquisition methods and applications in neuroimaging studies.What is the fundamental relationship between magnetization transfer and relaxation?
Biological tissues are heterogeneous spin systems that contain a large variety of molecules including free water, cellular membranes, solute proteins, metabolites, and others. The protons of these molecules evolve in different magnetic environments, and they may exchange magnetization over the time course of an MRI experiment, either through chemical exchange processes (i.e. physical exchange of a proton from one molecule to the other) or by through-space dipolar coupling (i.e. exchange of spin polarization) [1]. The MRI signal measured at conventional echo times (millisecond range) arise from free water magnetization, but nevertheless this signal carries the signature of the molecular environment the water protons have evolved through and exchanged with. In the fast-exchange limit between two proton populations (i.e. when the exchange rate is much faster than the intrinsic relaxation rates), the magnetization exchange so fast that their dynamics can be described by a single-exponential model and the observed longitudinal relaxation is the weighted average of the intrinsic relaxation rates [2,3]. This implies that “free water” relaxation globally reflects on the multiple contributions of different types of protons, including water protons in different magnetic environments and other fast-exchanging non water protons. This simple concept explains why MRI is so versatile in providing soft tissue contrast and why is has become particularly useful to distinguish various physio-pathological processes in the clinics. It also underlines that magnetization transfer effects (in their broad meaning) are important driving mechanisms of relaxation in biological tissues.When the exchange processes are not in the fast-exchange limit, it is necessary to account explicitly for additional proton pools in the biophysical model and the transfer of magnetization between these pools is described by cross-relaxation terms in the equations describing the magnetization dynamics of such systems [2,4,5]. This may lead to multi-exponential relaxation behavior of the free water signal measured in biological tissues [6,7], and most importantly this effect shall be taken into account to ensure reproducible measurement of the “free water” relaxation.
Magnetization transfer contrast is targeted to motion-restricted (“immobile”) macromolecules.
Magnetization transfer (MT) MRI refers to the exchange of magnetization between motion-restricted (a.k.a. semi-solid or “immobile”) macromolecular protons (MPs) and mobile free water protons (WPs) [8–10]. MPs exhibit a broad NMR spectrum (corresponding to a ~microsecond T2) because of non-zero time-averaged dipolar interactions. WPs have a sharp spectrum (long T2) and are commonly detectable using MRI. In contrast, chemical exchange saturation transfer (CEST) is targeted to molecules of interest that are solute, with a higher mobility than MPs, leading to a ~millisecond T2 and associated with a relatively sharp spectrum. This lecture is dedicated to MT and will not cover CEST related effects.MT effects may occur in various experimental scenarios [2], including selective inversion recovery [11,12] and saturation transfer techniques [8,9]. The most common MT experiment relies on selective saturation of MPs, achieved using off-resonance RF irradiation, followed by readout of the MRI signal coming from the WPs. In such experiments the WP MRI signal is attenuated because of MT, hence allowing for indirect detection of MPs.
Modeling MT and inhomogeneous MT (ihMT)
The binary spin bath (BSB) or two-pool model consists of a single WP pool in exchange with a single MP pool. It is the most common model used to described MT MRI data and will be presented in this course. In is important to note that liquid- and solid-state MR physics are different. Whereas the Bloch equations apply to mobile spins and implicitly correspond to a Lorentzian lineshape, solid spins shall be modeled differently. They are commonly assumed to have a gaussian lineshape, and for MPs contained in biological tissues a super-Lorentzian lineshape model was proposed, corresponding to an isotropic distribution of semi-solid macromolecules within the tissue [13,14]. In addition, MPs have a sustained non-zero dipolar interaction which provides additional degrees of freedom in the energy states distribution of the spin system. This leads to the consideration of an additional magnetization order, the dipolar order, to describe the magnetization dynamics of the spin system [13,15]. Dipolar order is coupled with Zeeman order (i.e. the classical magnetization) under off-resonance RF irradiation according to the Redfield-Provotorov theory [2,15] and shall be accounted for in the BSB model when dealing with MT experiments. Of note, the coupling between Zeeman and dipolar order vanishes for on-resonance excitation and when a symmetric dual-sided off-resonance RF irradiation is applied.This is the origin of the inhomogeneous MT (ihMT) technique which isolates the dipolar order contribution to the MT effects by comparing single- and dual-offset MT experiments [16,17]. Since dipolar order has its own longitudinal relaxation time, T1D, ihMT is a dipolar order imaging technique that is weighted by T1D. ihMT has found applications in neuroimaging studies because of its high specificity for myelin.
Acknowledgements
I thank my colleagues, collaborators, and all other researchers with whom I have had highly stimulating scientific discussions about MT, ihMT, relaxation and brain microstructure.References
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Other ISMRM courses on ihMT or related topics from previous years:
1. Duhamel G. Magnetization Transfer Techniques. ISMRM 2019. Weekend Educational Session. Myelin. https://www.ismrm.org/19/program_files/WE12.htm
2. Girard OM. ihMT Principles & Applications. ISMRM 2020. Weekend Educational Session. Signal Enhancement: The Power & the Glory. https://www.ismrm.org/20/program_files/WE18.htm
3. Girard OM. Magnetization Transfer. ISMRM 2021. Weekend Educational Session. Brain Microstructure. https://www.ismrm.org/21/program-files/WE-32.htm
4. Alsop D. MT: Principles & Methods. ISMRM 2022. Weekend Course. Microstructure: Relaxation, Magnetization Transfer & Susceptibility. https://www.ismrm.org/22/program-files/WE-13.htm