Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) can play a key role in understanding neurobiological mechanisms of diseases that affect the human brain. The specific changes that occur... Show moreDiffusion-weighted magnetic resonance spectroscopy (DW-MRS) can play a key role in understanding neurobiological mechanisms of diseases that affect the human brain. The specific changes that occur within neurons can be reflected as changes in the diffusivity of tNAA, whereas the changes in glial cells can cause pronounced changes in the diffusivities of tCr and tCho. This information combined with that obtained from diffusion tensor imaging (DTI) and other MRI tools can help elucidate various disease processes in the future. The main purposes of this thesis are (i) to investigate neuroanatomy in vivo with DW-MRS, (ii) to develop methodology to enable future clinical applications of the technique in human brain in vivo, and (iii) to characterize the microstructural deficit in neuropsychiatric systemic lupus erythematous (NPSLE) with DW-MRS and other microstructural tools such as DTI and magnetization transfer imaging. The studies presented in this thesis show the robustness and clinical relevance of microstructural information obtained via DW-MRS. The contributions of this thesis such as the optimized acquisition protocols for single volume DW-MRS, the robust DW-CSI and DW-MRS post-processing pipelines that comprise information from DTI, will all facilitate the applications of DW-MRS both for basic neuroscience research and clinical research studies. Show less
The aims of this thesis were to gain insight into specific disease processes in Huntington__s Disease (HD) and to identify biomarkers. To achieve these aims, cognitive functioning, structural brain... Show moreThe aims of this thesis were to gain insight into specific disease processes in Huntington__s Disease (HD) and to identify biomarkers. To achieve these aims, cognitive functioning, structural brain characteristics and intrinstic functional brain connectivity of premanifest and early HD subjects were examined. Cortical, subcortical and the intermediate white matter brain tissue shows evidence of structural and functional decline. We found evidence that disease processes, such as altered metabolism, excessive iron accumulation and cell loss, play a role in the changes. We conclude that changes occur throughout the brain from the earliest disease phase onwards. Hence, both premanifest and manifest HD should not be regarded as a disorder of the basal ganglia, but as a disease affecting the whole brain. Candidate biomarkers that have the potential to objectively reflect the early changes and the progressive nature of the disease are measures of subcortical atrophy, integrity of white matter pathways and of intrinsic functional brain connectivity. Iron, creatine, and N-acetylaspartate concentrations in the caudate nucleus and putamen may prove to be useful as markers of disease state for objectifying transitional disease processes from premanifest to manifest HD. Visuospatial working memory could be applied as a state marker for stage two HD. Show less
The aim of this thesis was to find potential MRI biomarkers for Huntington__s disease (HD). Therefore, after an overview of the current literature on MRI biomarkers, followed by examinations of... Show moreThe aim of this thesis was to find potential MRI biomarkers for Huntington__s disease (HD). Therefore, after an overview of the current literature on MRI biomarkers, followed by examinations of volumetric MRI, magnetization transfer imaging (MTI), diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) were applied in patients in different disease stages of HD. The main conclusions demonstrate that choosing the optimal biomarker for evaluating therapeutic effects is dependent on the disease stage and therapeutic compound. To evaluate the premanifest stages of the disease volumetric MRI and DTI are most suitable. When the transition period is the desired timeframe for evaluation, also MRS can be very useful, especially if the compound in question has a direct potential influence on certain pathogenic pathways which in turn have an impact on specific metabolites. Future research should focus on combining multiple imaging techniques; __multimodal imaging__. A composite MRI biomarker has the potential to distinguish between disease groups more accurately than a single biomarker and in this way improve the evaluation of therapeutic compounds. Show less
Brain function has long been the realm of philosophy, psychology and psychiatry and since the mid 1800s, of histopathology. Through the advent of magnetic imaging in the end of the last century, an... Show moreBrain function has long been the realm of philosophy, psychology and psychiatry and since the mid 1800s, of histopathology. Through the advent of magnetic imaging in the end of the last century, an in vivo visualization of the human brain became available. This thesis describes the development of two unique techniques, imaging of diffusion of water protons and manganese enhanced imaging, that both allow for the depiction of white matter tracts. The reported studies show, that these techniques can be used for a three-dimensional depiction of fiber bundles and that quantitative measures reflecting fiber integrity and neuronal function can be extracted from such data. In clinical applications, the potential use of the developed methods is illustrated in human gliomas, as measure for fiber infiltration, and in spinal cord injury, to monitor potential neuroprotective and __regenerative medication. Show less
