On the track of the brain's microstructure : myelin water imaging using quantitative MRI

Abstract

Conventional quantitative magnetic resonance imaging (MRI), for example monoexponential determination of the relaxation times T1 and T2, is sensitive to the various pathologies of myelinated tissue in the brain. However, it gives relatively unspecific information about the underlying nature of the disease. A parameter that directly correlates with the integrity of the myelin sheath is the so-called myelin water fraction (MWF). Based on multi-component analysis of non-invasive quantitative MRI measurements, mapping of the MWF becomes feasible and proved to be useful for studying demyelination and remyelination processes in the course of multiple sclerosis (MS) and other myelin related pathologies. Common myelin water imaging techniques often suffer from a lack of volume coverage due to their 2D acquisition schemes. This thesis focuses on the development of new myelin water mapping procedures, especially on fast 3D MRI measurements that provide whole brain coverage. In chapter 2, an MWF mapping technique based on balanced steady-state free precession (bSSFP) sequences is introduced. An extended bSSFP signal equation, which is based on a two-pool water model describing brain tissue, is derived to determine typical multi-compartment parameters, including the MWF, of healthy subjects. Possible influences of magnetization transfer effects, infinite radiofrequency pulses and B0/B1 inhomogeneities are discussed extensively. Chapter 3 introduces a 3D acquisition scheme based on multi-gradient-echo (mGRE) pulse sequences that is applied for sampling multi-component T2* decays in the human brain of healthy volunteers and MS patients. Quantitative myelin water maps are generated based on analysis of T2* spectra. Chapter 4 discusses possible adaptations and modifications of the proposed procedure from chapter 3 when moving to higher main magnetic field strengths. The effects of B0 inhomogeneities on the data sets and possible correction methods are additionally covered in this part of the thesis. Finally, the crucial role of accurate B1 and B0 imaging and the influences on myelin water imaging are revisited in chapter 5. A solution to simultaneous mapping of B1 and B0 is presented that might help to overcome systematic error sources in MWF mapping in the future.