In ALS, advanced magnetic resonance imaging (MRI) techniques are increasingly used to investigate the underlying pathology. In this study, the technique of voxel-based morphometry (VBM) was applied to 3-D MRI data in ALS patients to localize regional grey and white matter changes. Twenty-two ALS patients (mean age 58+/-9 years) with clinically definite ALS by revised El Escorial criteria were studied. None of the patients had any signs of associated frontotemporal dementia. High-resolution 3-D MRI data sets of the whole brain, collected on a 1.5 T scanner, were analysed by statistical parametric mapping (SPM) and VBM in comparison to an age-matched normal data base consisting of 22 healthy volunteers (mean age 59+/-11 years), for grey matter and white matter segments separately. Global brain atrophy was assessed by calculation of brain parenchymal fractions (BPF). In ALS patients, BPF were significantly reduced compared to controls (p = 0.0003), indicating global brain atrophy. Regional decreases of grey matter density were found in the ALS patients at corrected p<0.01 in the right-hemispheric primary motor cortex (area of the highest Z-score) and in the left medial frontal gyrus. Furthermore, regional white matter alterations were observed along the corticospinal tracts bilaterally and in multiple smaller areas including corpus callosum, cerebellum, frontal and occipital subcortical regions. Besides considerable global atrophy in ALS, the topography of ALS-associated cerebral morphological changes could be mapped using VBM, in particular white matter signal changes along the bilateral corticospinal tracts, but also in extra-motor areas. VBM might be a potential tool to visualize disease progression in future longitudinal studies.

White matter connectivity in the human brain can be mapped by diffusion tensor magnetic resonance imaging (DTI). After reconstruction, the diffusion tensors, the diffusion amplitude and the diffusion direction can be displayed on a morphological background. Consequently, diffusion tensor fibre tracking can be applied as a non-invasive in vivo technique for the delineation and quantification of specific white matter pathways. The aim of this study was to show that normalization to the Montreal Neurological Institute (MNI) stereotaxic standard space preserves specific diffusion features. Therefore, techniques for tensor imaging and fibre tracking were applied to the normalized brains as well as to the group averaged brain data. A normalization step of individual data was included by registration to a scanner- and sequence-specific DTI template data set which was created from a normal database transformed to MNI space. The algorithms were tested and validated for a group of 13 healthy controls.

Different motor neuron disorders (MNDs) are mainly defined by the clinical presentation based on the predominance of upper or lower motor neuron impairment and the course of the disease. Magnetic resonance imaging (MRI) mostly serves as a tool to exclude other pathologies, but novel approaches such as diffusion tensor imaging (DTI) have begun to add information on the underlying pathophysiological processes of these disorders in vivo. The present study was designed to investigate three different rare MNDs, i.e., primary lateral sclerosis (PLS, N = 25), hereditary spastic paraparesis (HSP, N = 24), and X-linked spinobulbar muscular atrophy (X-SBMA, N = 20), by use of whole-brain-based DTI analysis in comparison with matched controls. This analysis of white matter (WM) impairment revealed widespread and characteristic patterns of alterations within the motor system with a predominant deterioration of the corticospinal tract (CST) in HSP and PLS patients according to the clinical presentation and also in patients with X-SBMA to a lesser degree, but also WM changes in projections to the limbic system and within distinct areas of the corpus callosum (CC), the latter both for HSP and PLS. In summary, DTI was able to define a characteristic WM pathoanatomy in motor and extra-motor brain areas, such as the CC and the limbic projectional system, for different MNDs via whole brain-based FA assessment and quantitative fiber tracking. Future advanced MRI-based investigations might help to provide a fingerprint-identification of MNDs.

An impairment of central somatosensory processing is assumed in restless legs syndrome (RLS). Although functional neuroimaging in RLS gave evidence to the presence of widespread functional changes in various brain areas, structural changes at the cortical level were not reported to be RLS-associated to date. Here, an analysis of high-resolution three-dimensional magnetic resonance imaging (MRI) was performed in 63 patients with idiopathic RLS by use of optimized voxel-based morphometry, in order to investigate if cortical areas might be altered in volume at group level according to the phenomenology of RLS. The comparison of the RLS patients versus controls yielded significant regional decreases of gray matter volume at corrected P < 0.05 in the bihemispheric primary somatosensory cortex, which additionally extended into left-sided primary motor areas. All clusters correlated both with the severity of RLS symptoms and with disease duration. These results, for the first time, give in vivo evidence to structural neocortical gray matter alterations in RLS patients. The alterations in the sensorimotor cortices might add to the pathophysiological concepts of idiopathic RLS.

Background: Information on anatomical connectivity in the brain by measurements of the diffusion of water in white matter tracts lead to quantification of local tract directionality and integrity.