Diffusion tensor imaging: study of white matter connection and advanced MRI sequence development

Magnetic resonance imaging (MRI) is an imaging technique able to produce high quality images of the human body without ionizing radiation. Over years, MRI has been constantly improved, and advanced MRI techniques able to investigate structure and physiology of the human body have been developed. In particular, diffusion MRI is an advanced technique, which, sensing water molecules movement and its direction, provides quantitative information about microstructural properties of fiber bundles in white matter (WM). All projects developed in this thesis were focused on diffusion MRI and consequently on the study of WM organization. The first project was focused on investigating WM differences between healthy subjects, patients affected by Vascular Dementia (VaD) and Alzheimer disease (AD). Since VaD and AD neuropsychological profiles often overlap and anatomical changes do not always correlate with a specific type of dementia, differentiating between them results difficult. Therefore, in order to provide quantitative imaging biomarkers specifically sensitive to AD or VaD, a voxel wise analysis on the whole WM was performed on a total of 93 subjects (31 AD, 27 VaD and 35 healthy control). WM alteration patterns considered useful in distinguishing between VaD and AD emerged from the analysis. In particular, parahippocampal gyri and corpus callosum showed different anterior/posterior alteration patterns specific to pathology, while thalamic radiation impairment seemed to be characteristic of VaD, because these patients showed alterations in this area compared both to AD and HC but no alterations were found in AD. Altogether these findings revealed an impairment in WM bundles involved in cognition and in the cerebro-cerebellar connectivity. In the second project, cerebro-cerebellar connectivity was studied with the aim of clarifying cerebellar involvement in cognition and describing cerebro-cerebellar loop structure. Advanced MRI tractography was used to reconstruct and quantitatively describe the cortico-ponto-cerebellar (CPC) pathway in human in vivo. From the analysis emerged that the CPC pathway is mainly involved in the connection of cognitive cerebral and cerebellar areas. Furthermore, in order to study the whole cerebro-cerebellar loop, which is composed of the CPC and the cerebellothalamo-cortical (CTC) pathway, these results were compared with the ones already obtained in a previous study focused on CTC. Both pathways resulted to be interested in connecting cognitive areas. A difference in terms of cerebral areas reached by the two pathways suggests an asymmetry of the cerebro-cerebellar loop regarding cognitive tasks. Whereas findings during motor tasks suggest a symmetrical communication between the cerebrum and the cerebellum. Even though results obtained from post processing of diffusion data revealed important information, DTI suffers from resolution issues due to the trade off between voxel size and SNR, with voxel dimension in the order of important details in the structure of the addressed WM bundles. Therefore, diffusion analysis would benefit from higher resolution data. Here, in order to partially resolve the resolution problem, a sequence able to acquire high-resolution images using non-coplanar radio frequency pulses, was developed. Data acquired with this sequence showed good signal-to-noise ratio values and an anatomically reliable reconstruction of color-coded maps of fractional anisotropy. All these projects gave interesting information about WM structure, along with new advanced investigation tools. Further experiments where all the techniques, here applied separately, can be applied together, would be useful in order to improve results quality and perform new hypothesis about WM structure and properties. Index Introduction . 1 Chapter 1: Introduction to magnetic resonance . 4 1.1 Opportunity in MRI . 4 1.2 Physics of MRI. 4 1.3 From physics to signal . 8 1.4 Image reconstruction . 9 1.5 Basic MRI sequences . 11 1.6 Image contrast . 13 1.7 Advanced MRI techniques . 14 Chapter 2: Diffusion MRI . 17 2.1 Physics and acquisition of diffusion imaging . 17 2.2 Diffusion weighted imaging . 21 2.3 Diffusion tensor imaging . 22 2.4 Tractography . 24 Chapter 3: White matter differences between Alzheimer Disease and Vascular Dementia . 27 3.1 Alzheimer Disease and Vascular Dementia: an overview . 27 3.2 Tract based spatial statistics . 29 3.3 Analysis pipeline . 30 3.4 Results . 32 3.5 White matter bundles useful in the diagnosis . 37 Chapter 4: Tractography of the cortico-ponto-cerebellar pathway in human in vivo . 44 4.1 Cerebro-cerebellar connectivity . 44 4.2 Reconstruction method . 47 4.3 Results: cortico-ponto-cerebellar pathway analysis and quantification . 51 4.4 Hypothesis of cerebro-cerebellar connections . 54 4.5 Involvement of the pathway in the cerebro-cerebellar loop . 58 Chapter 5: Implementation and application of a zoom diffusion weighted sequence . 63 5.1 Zoom: theory and advantages. 63 5.2 Implementation . 65 5.3 Acquisition . 70 5.4 Results and comparison at 3T . 74 5.5 Preliminary results at 9.4T. 79 Chapter 6: General conclusions . 81 Bibliography . 83