Abstract
Myelin specific Magnetic Resonance Imaging (MRI) is challenged by the very short transverse relaxation time characteristic of the myelin sheath. The highly organized lipid multi-layered stack ultrastructure of the myelin membrane results in peculiar magnetic properties of the methylene protons along lipid chains, including unaveraged dipolar interactions. Off-resonance radiofrequency saturation can induce a particular arrangement of these dipolar interactions, called dipolar order. Inhomogeneous Magnetization Transfer (ihMT) allows the isolation of signal arising from protons with a detectable dipolar order, thus providing in the context of Central Nervous System (CNS) imaging enhanced selectivity to myelinated tissues. The ihMT signal is weighted by T1D, the dipolar order relaxation time, itself driven by slow molecular dynamics and tissue microstructure. In this context, this thesis investigated the possibility to isolate the various T1D components encountered in CNS tissues by filtering the ihMT signal. Then, the specificity to myelination of various ihMT T1D-filters was assessed by employing histological references for myelin imaging, and was compared with other quantitative MR metrics. Furthermore, the sensitivity of ihMT T1D-filters to myelin alteration was demonstrated in two mouse models: the acute cuprizone model, and the lysophosphatidylcholine focal demyelination model in the spinal cord. Finally, with the objective of obtaining quantitative parameters more informative of the myelin membrane status, a quantitative ihMT framework using a matrix exponential approach was developed and used in experiments performed on a surrogate of the myelin membrane