Biophysical mechanisms of susceptibility in the human cortex

Quantitative susceptibility mapping (QSM) is a novel MRI technique that has demonstrated approximately 10-times increased white-gray matter contrast in the human brain compared to conventional MRI. Additionally, QSM is a noninvasive imaging technology that provides a true quantitative measure reflecting a basic physical property of magnetism in matter. Therefore, QSM is of high interest for quantitatively assessing iron deposition and microstructural tissue changes in vivo. Recent attempts to reliably assess the susceptibility in the cortex were hindered by magnetic susceptibility artifacts which typically occur at the tissue-skull interface. This project will incorporate strategies to overcome this problem and to assess the susceptibility in the cortex in a more refined and stable manner. Additionally, this project aims at a better understanding of the formation of bulk susceptibility by developing a biophysical model that takes also the composition and the cytoarchitecture of the cortex into account. Besides paramagnetic iron deposition, diamagnetic myelin and the orientation of fiber bundles with respect to the main magnetic field will be considered. The experiments will be performed at ultra-high field strength using a novel MRI pulse sequence and dedicated scanner hardware. The feasibility of QSM in the cortex will enable the assessment and depiction of disease related tissue changes which is expected to have strong impact in various inflammatory and neurodegenerative diseases. Abnormally increased iron deposition was found in the motor cortex of amyotrophic lateral sclerosis patients (ALS), and seems to be linked to amyloid beta plaques in Alzheimers disease (AD) and to cortical lesions in multiple sclerosis (MS). However, cortical iron accumulation in these conditions cannot be detected by any MRI sequences yet. Therefore, further development of QSM and modeling of susceptibility as outlined in this project is expected to provide new applications of this technique and new insights in to the biophysical mechanism of cortical iron accumulation in these diseases.