MICROSTRUCTURE AND CONNECTIVITY OF THE CEREBELLUM WITH ADVANCED DIFFUSION MRI IN HEALTH AND PATHOLOGY

The cerebellum contains most of the central nervous system neurons and it is classically known to be a key region for sensorimotor coordination and learning. However, its role in higher cognitive functions has been increasingly recognised, thus raising the interest of neuroscience and neuroimaging communities. Despite this, knowledge of cerebellar structure and function is still incomplete and the interpretation of experimental results is often problematic. For these and also technical reasons the cerebellum is still frequently disregarded in magnetic resonance imaging (MRI) studies. Therefore, the principal aim of this work was to use MRI to investigate cerebellar microstructure and macrostructural connectivity in health and pathology, focusing also on technical aspects of image acquisition. The starting point of each project described in the present thesis were techniques, models and pipelines currently accepted in clinical practice. The meeting of inadequacies or problems of such techniques raised questions that pushed research to a more fundamental level. This thesis has three main contributions. The first part presents a clinical study of cerebellar involvement in processing speed deficits in multiple sclerosis, where combined tractography and network science highlighted the importance of the cerebellum in patients’ cognitive performance. Then a deeper investigation conducted on high-quality diffusion MRI data with advanced diffusion signal models showed that subregions of the cerebellar cortex are characterised by different microstructural features: this represents one of the very first attempts to use diffusion MRI to face the widespread idea of cerebellar cortex uniformity, which has been recently challenged by findings from other research fields, thus providing new perspectives for the study of cerebellar information processing in health and pathology. Finally, the emerging technical problems that hamper the study of small structures within the cerebellum were tackled by developing dedicated acquisition protocols that exploit reduced field-of-view techniques for 3T and 7T MRI scanners.