Deciphering the physical contrasts mechanisms of myelin-associated inhomogeneous magnetization transfer by field- and orientation-dependent MR experiments

• Applicant: Dr. Niklas Wallstein
• Subject Area: Medical Physics, Biomedical Technology ; Biophysics
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 583330474

Magnetic resonance imaging has become the primary modality for myelin imaging, with the objective of observing de- and remyelination processes. Myelin refers to the isolating multilayered sheaths of lipid-protein bilayers that surround the axons, particularly in white matter. A degradation of myelin is associated with a variety of neurodegenerative diseases, indicating the urgent need for the development of innovative techniques to non-invasively quantify the tissue's myelin content. Several myelin-sensitive MRI techniques are currently available, each with distinct strengths and limitations – among them the inhomogeneous magnetization transfer (ihMT). IhMT represents an extension of conventional MT imaging, providing different contrasts between tissues than MT by isolating 'dipolar order effects' – with increased sensitivity to myelin. To develop reliable applications based on 'ihMT-imaging' for research and clinics, it is essential to have a complete physical understanding of the underlying contrast mechanism. This necessitates a greater emphasis on fundamental research, as proposed by the ‘MONUMENT’ project. To elaborate on this, ihMT is intrinsically weighted by tissue’s dipolar order relaxation times T1D according to the theoretical framework based on biophysical compartment models containing ‘mobile’ and ‘semi-solid’ pools, which are additionally equipped with ‘dipolar order reservoirs’ (described by the Provotorov theory). The ‘MONUMENT’ project will challenge these biophysical models regarding two fundamental aspects: (I) In the realm of the recent ongoing development of newer lower-field MR systems, the influence of the external field strength on the observed ihMT effect and T1D relaxation times – including the limiting case of low-field investigations (of a few mT), will be analyzed in a comprehensive way. Therefore, low field investigations of ihMT phantoms and tissues will be conducted and quantitively analyzed. (II) The anisotropy of ihMT, i.e., the influence of the main-fiber-to-field orientation, will be characterized using ex vivo tissue samples under direct sample reorientation enabled by established custom-made coil setups at different clinical field strengths and temperatures. Thus, it can be anticipated that these two main objectives will lead to a better understanding of ihMT, in terms of (i) the validity regime of the biophysical models and the ihMT effect at low-fields, and (ii) the degree of ihMT- and T1D-anisotropy in highly ordered tissues. The targeted deciphering of the physical contrast mechanism of myelin-associated ihMT will facilitate a more profound comprehension of the pitfalls inherent in modelling, as well as enable a meticulous analysis of the required complexity. Conversely, this will also reveal the inadequacies of simplified 'pool' models. Ultimately, this research will enhance the reliability of the translation of ihMT-weighted images into biophysical model parameters, such as the myelin content.

• DFG Programme: Fellowship
• International Connection: Canada
• Host: Professor Dr. Carl Michal