Upper and extra-motoneuron involvement in early motoneuron disease: a diffusion tensor imaging study.

Motoneuron disease is a term encompassing three phenotypes defined largely by the balance of upper versus lower motoneuron involvement, namely amyotrophic lateral sclerosis, primary lateral sclerosis and progressive muscular atrophy. However, neuroradiological and pathological findings in these phenotypes suggest that degeneration may exceed the neuronal system upon which clinical diagnosis is based. To further delineate the phenotypes within the motoneuron disease spectrum, this controlled study assessed the upper- and extra-motoneuron white matter involvement in cohorts of patients with motoneuron disease phenotypes shortly after diagnosis by comparing diffusion tensor imaging data of the different cohorts to those of healthy controls and directly between the motoneuron disease phenotypes (n = 12 for each cohort). Furthermore, we acquired follow-up data 6 months later to evaluate fractional anisotropy changes over time. Combined use of diffusion tensor tractography of the corticospinal tract and whole-brain voxel-based analysis allowed for comparison of the sensitivity of these techniques to detect white matter involvement in motoneuron disease. The voxel-based analysis demonstrated varying extents of white matter involvement in different phenotypes of motoneuron disease, albeit in quite similar anatomical locations. In general, fractional anisotropy reductions were modest in progressive muscular atrophy and most extensive in primary lateral sclerosis. The most extensive patterns of fractional anisotropy reduction were observed over time in the voxel-based analysis, indicating progressive extra-motor white matter degeneration in limb- and bulbar onset amyotrophic lateral sclerosis and in progressive muscular atrophy. The observation of both upper motor and extra-motoneuron involvement in all phenotypes of motoneuron disease shortly after diagnosis suggests that these are all part of a single spectrum of multisystem neurodegenerative disease. Voxel-based analysis was more sensitive to detect longitudinal changes than diffusion tensor tractography of the corticospinal tract. Voxel-based analyses may be particularly valuable in the evaluation of motor and extra-motor white matter involvement in the early symptomatic stages of motoneuron disease, and for monitoring the spread of pathology over time.

The effect of template selection on diffusion tensor voxel-based analysis results.

Diffusion tensor imaging (DTI) is increasingly being used to study white matter (WM) degeneration in patients with psychiatric and neurological disorders. In order to compare diffusion measures across subjects in an automated way, voxel-based analysis (VBA) methods were introduced. In VBA, all DTI data are transformed to a template, after which the diffusion measures of control subjects and patients are compared quantitatively in each voxel. Although VBA has many advantages compared to other post-processing approaches, such as region of interest analysis or tractography, VBA results need to be interpreted cautiously, since it has been demonstrated that they depend on the different parameter settings that are applied in the VBA processing pipeline. In this paper, we examine the effect of the template selection on the VBA results of DTI data. We hypothesized that the choice of template to which all data are transformed would also affect the VBA results. To this end, simulated DTI data sets as well as DTI data from control subjects and multiple sclerosis patients were aligned to (i) a population-specific DTI template, (ii) a subject-based DTI atlas in MNI space, and (iii) the ICBM-81 DTI atlas. Our results suggest that the highest sensitivity and specificity to detect WM abnormalities in a VBA setting was achieved using the population-specific DTI atlas, presumably due to the better spatial image alignment to this template.

Construction of a stereotaxic DTI atlas with full diffusion tensor information for studying white matter maturation from childhood to adolescence using tractography-based segmentations.

Reconstruction of white matter (WM) fiber tracts based on diffusion tensor imaging (DTI) is increasingly being used in clinical and research settings to study normal and pathological WM tissue as well as the maturation of this WM tissue. Such fiber tracking (FT) methodology, however, is highly dependent on the manual delineation of anatomical landmarks and the algorithm settings, often rendering the reproducibility and reliability questionable. Predefining these regions of interest on a fractional anisotropy (FA) atlas in standard space has already been shown to improve the reliability of FT results. In this paper, we constructed a new DTI atlas, which contains the complete diffusion tensor information in ICBM152 coordinates. From this high-dimensional DTI atlas, and using robust FT protocols, we reconstructed a large number of WM tracts. Subsequently, we created tract masks from these fiber tract bundles and evaluated the atlas framework by comparing the reproducibility of the results obtained from our standardized tract masks with regions-of-interest labels from the conventional FA-based WM atlas. Finally, we assessed laterality and age-related WM changes in 42 normal subjects aged 0 to 18 years using these tractography-derived tract segmentations. In agreement with previous literature, we observed an FA increase with age, which was mainly due to the decrease of perpendicular diffusivity. In addition, major functional pathways in the language, motor, and limbic system, showed a significant asymmetry in terms of the observed diffusion metrics.

Quantitative diffusion tensor imaging in amyotrophic lateral sclerosis: revisited.

Voxel-based analyses (VBA) are increasingly being used to detect white matter abnormalities with diffusion tensor imaging (DTI) in different types of pathologies. However, the validity, specificity, and sensitivity of statistical inferences of group differences to a large extent depend on the quality of the spatial normalization of the DTI images. Using high-dimensional nonrigid coregistration techniques that are able to align both the spatial and orientational diffusion information and incorporate appropriate templates that contain this complete DT information may improve this quality. Alternatively, a hybrid technique such as tract-based spatial statistics (TBSS) may improve the reliability of the statistical results by generating voxel-wise statistics without the need for perfect image alignment and spatial smoothing. In this study, we have used (1) a coregistration algorithm that was optimized for coregistration of DTI data and (2) a population-based DTI atlas to reanalyze our previously published VBA, which compared the fractional anisotropy and mean diffusivity maps of patients with amyotrophic lateral sclerosis (ALS) with those of healthy controls. Additionally, we performed a complementary TBSS analysis to improve our understanding and interpretation of the VBA results. We demonstrate that, as the overall variance of the diffusion properties is lowered after normalizing the DTI data with such recently developed techniques (VBA using our own optimized high-dimensional nonrigid coregistration and TBSS), more reliable voxel-wise statistical results can be obtained than had previously been possible, with our VBA and TBSS yielding very similar results. This study provides support for the view of ALS as a multisystem disease, in which the entire frontotemporal lobe is implicated.

Quantitative diffusion tensor imaging in amyotrophic lateral sclerosis.

OBJECTIVE: Aim of present study was to evaluate changes in diffusion tensor imaging (DTI) parameters in the whole brain of 28 patients with amyotrophic lateral sclerosis (ALS) compared to 26 healthy controls. METHODS: In both fibertracking and voxel-based analysis, quantitative comparisons of the diffusion parameters between ALS patients and controls were performed. Correlation analyses of diffusion parameters and disease duration and disease severity were performed. A second DTI examination was acquired, allowing the evaluation of the effect of disease progression on the diffusion parameters. RESULTS: Fibertracking analysis revealed that especially the precentral part of the corticospinal tract (CST) was impaired. In the voxel-based analysis, it was shown that changes of diffusion parameters occurred throughout the brain, including frontal, temporal and parietal lobes. Disease severity was inversely correlated with the fractional anisotropy (FA). In the follow-up examination, a further decline of FA over time could be demonstrated in the CST as well as in the whole brain white matter. INTERPRETATION: This study provides support for the view of ALS as being a multisystem degenerative disease, in which abnormalities of extra-motor areas play an important role in the in vivo physiopathology.