Magnetic Properties of Normal Appearing Brain White Matter in Multiple Sclerosis

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Magnetic resonance imaging (MRI) has significantly contributed to our understanding of brain pathology in multiple sclerosis (MS), however conventional MRI often fails to explain the clinical condition of patients which is commonly known as the clinico-radiological paradox. Several histological studies have suggested that the otherwise normal appearing white matter (NAWM) is affected by a diffuse inflammatory response and microglial activation. Consequently, great hope had been put on quantitative MRI techniques such as diffusion tensor imaging or magnetization transfer imaging. However, it turned out that the sensitivity and specificity of these techniques do not allow to probe these changes in NAWM on an individual level.In this proposal, we aim at assessing MS related tissue changes in NAWM using quantitative susceptibility mapping (QSM). QSM is a new and promising MRI technique which has experienced a breakthrough in recent years. In contrast to conventional MRI, which provides relaxation based image contrast only, QSM allows to calculate and map the magnetic susceptibility of the brain utilizing the phase information from gradient echo MRI scans. There is a lot of evidence, that the magnetic susceptibility is highly sensitive to pathological conditions of MS including inflammation, demyelination, and focal accumulation of iron. We expect that QSM in NAWM could provide further insight into MS pathology and therefore could serve as a new marker for diagnosis and progression of MS.This international cooperation project will be conducted by Graz (Austria) and Jena (Germany) in a collaborative manner. Over a period of three years, both centers will recruit in total 60 MS patients and 60 healthy controls and will perform QSM at baseline and after one year using exactly the same MR machinery. The magnetic susceptibility in normal white matter and NAWM will be investigated in more detail by considering also the bound pool fraction as a marker of myelin content and by determining the isotropic and anisotropic components of the susceptibility. In the MS patients, regional tissue characterization by QSM will be compared to healthy controls and will be related to clinical and cognitive conditions. We expect that the complementary expertise that is provided by Graz and Jena with respect to QSM, quantitative magnetization transfer, and MS research will contribute to a successful project.