Development and application of techniques for quantitative voxel based morphometry

The use of standard brain atlases is well established in the MR community, but none of the commonly utilised standard brains or atlases, such as MNI305 or ICBM152, provide quantitative information. Within the framework of quantitative MRI of the brain, which has gained much importance in the last few years, this work reports on the development of the first quantitative brain atlas for tissue water content. A fast and reliable method for quantitatively measuring the absolute water content of the brain, developed previously in-house, was used and sequence protocols were optimised to achieve the highest precision and accuracy of the individual measurements. Water content, T1 and T2* were simultaneously mapped based on an acquired series of spoiled gradient echo images with different T2*-weighting (QUTE). Based on the quantitative information of these maps, three brain atlases were developed, representative for a young and healthy population with an average age of 33.5 + 12.07 years. Data were transformed into a common stereotactic space and linearly averaged to form the final atlases. Several approaches for atlas formation were extensively investigated and validated. Subsequently, the quantitative water content atlas was used as reference for the comparison of patients with pathological changes in the absolute water content of the brain to healthy volunteers. A voxel-wise comparison to the atlas was performed, using quantitative water content maps of patients suffering from multiple sclerosis (MS) and patients undergoing electro-convulsive therapy (ECT). Comparing water content maps of MS patients to the reference water content atlas, using a one-sample t-test, led to clearly defined WM lesions. During the course of ECT, small changes in the water content were found. In summary, the first quantitative water content brain atlas in vivo was developed in the current work and a voxel-wise comparison of diseases related to a change in the brain water content was performed. With the results presented and further improvements, quantitative MRI in combination with a quantitative water content brain atlas allows for a careful and quantitative interpretation of disease monitoring