Whole brain-based computerized neuroimaging in ALS and other motor neuron disorders

Abstract

Advanced neuroimaging applications to patients suffering from ALS and other motor neuron disorders (MND) have a high potential in terms of understanding the pathophysiology and visualizing the in vivo pathoanatomy of the diseases. In this context, particularly observer-independent computerized analyses of magnetic resonance imaging (MRI) data are of special interest since they overcome shortcomings of region-of-interest-based techniques. For three-dimensional structural T1-weighted MRI of the whole brain, voxel-based morphometry (VBM) has proven the most valuable approach to analyse regional volume alterations of the grey or white matter at group level. For the analysis of the white matter integrity with respect to tissue diffusivity and white matter connectivity including fibre tracking algorithms, diffusion tensor imaging (DTI) which can also be performed on a whole brain-basis is of the highest potential to date. Both VBM and DTI have been applied to various MND, in particular ALS, in multiple studies over recent years and have substantially broadened our knowledge about their in vivo pathoanatomy and mechanisms of neurodegeneration. Especially both the degree of damage to motor areas and the involvement of non-motor areas are of interest to be subjected to quantitative assessment, in order to establish quantitative surrogate markers for disease progression usable in clinical trials. Here, the technical state-of-the-art and the results of VBM and DTI studies in MND as the current state are reviewed, and future perspectives for further neuroimaging applications are highlighted.

Corpus callosum involvement is a consistent feature of amyotrophic lateral sclerosis

“…33 Beyond the minority of ALS cases with frank FTD, significant atrophy of either GM or WM is not typical. MRI is potentially more sensitive to such changes, and several studies have demonstrated widespread GM changes including regional overlap with our study 18,27,[34][35][36] (reviewed in reference 37 ). While the involvement of the temporal lobes we noted is in keeping with the known spectrum of cognitive and pathologic overlap with FTD, none of our subjects had overt cognitive impairment, and we do not draw any firm conclusions in the absence of formal neuropsychological assessment.…”

Accuracy of Conventional MRI in ALS

“…In a study of 80 ALS patients, Abe et al 21 found that 65% of patients and 51% of controls showed hyperintensity of the posterior limb of the internal capsule on both T2 and proton density sequences. Several recent reviews on the role of MRI as a biomarker for ALS have thus concluded that the finding of CST hyperintensity on T2, FLAIR or PD cannot be considered a reliable indicator because of its poor sensitivity and specificity [22][23][24] .…”

Neuroimaging of motor neuron diseases

“…In proton-density images, foci of frontal abnormalities were observed, indicating involvement of frontal projections. In addition, fluid-attenuated inversion recovery (FLAIR) images were slightly more sensitive in detecting CST signal alterations than T1w or T2w images (see Grosskreutz and colleagues for a review) [Grosskreutz et al 2008]. Also for the diagnosis of primary lateral sclerosis (PLS), MRI signs are described, that is, abnormalities (atrophy) in the precentral gyrus region and CST hyperintensities [Singer et al 2007].…”