Advanced magnetic resonance imaging techniques in brain diseases

In the last fifteen years considerable efforts have been dedicated to the statistical analysis of MR images to reveal subtle brain alterations in vivo. Nowadays several analytical methods aimed at investigating focal abnormalities in gray and white matter at group level are available. In particular, a technique called Voxel Based Morphometry (VBM) has been developed to detect gray matter atrophy. This technique has been extensively used to characterize neurological disorders, like Alzheimer and Parkinson diseases, and to investigate subtle differences related to handedness, sex or age in the healthy population. Several attempts to apply VBM technique to Diffusion Tensor Imaging (DTI) derived maps have been performed in the past. However many concerns have been raised about the sensitivity and precision of the direct application of VBM to DTI data (VBM-DTI). To address these issues other techniques have been developed, such as Tract-based Spatial Statistics (TBSS) which was firstly proposed in 2006. Nowadays TBSS is a widespread and effectively used technique that allows investigation of differences in DTI derived metric, like Fractional Anisotropy (FA), Axial Diffusivity (AD), Radial Diffusivity (RD) and Apparent Diffusion Coefficient (ADC). In this work, the potential of VBM analysis of structural MR images acquired at high resolution in mice, rat and human brain has been addressed. We focused on translational models of multiple sclerosis (MS) and Amyotrophic Lateral Sclerosis (ALS) as well as on clinical data of mild Traumatic Brain Injuries (mTBI) subsequent to car accident, falls or sports related trauma. In the latter case, DTI data were analyzed trough TBSS approach. We used Experimental Autoimmune Encephalomyelitis (EAE) induced in rats as translational model of MS, and a transgenic mouse (SOD1(G93A)) as translational model of ALS. In the experimental model of MS reported in the first part of this thesis, we focused on the identification, through VBM analysis, of Grey Matter atrophy in the cortical area of EAE rats to correlate atrophy with histological and functional MRI findings. In the second part of this thesis we focused on the definition of biomarkers in the framework of ALS. We aimed at defining imaging biomarkers (using both VBM and traditional region-of-interest based analysis) with the final goal of monitoring disease evolution and testing the efficacy of a stem cell based therapy. In the last part of this work, by applying TBSS techniques (and VBM-DTI), we aimed at defining DTI derived biomarkers in mTBI patients to unravel the pathophysiological finding of delayed performance deficits in patients after mild traumatic brain injury (mTBI). Our aim is to provide a framework for the understanding of mTBI pathology by the identification of MRI biomarkers predictive of long-term outcome.