Voxel based morphometry (VBM) allows objective and automated detection of structural changes in brains of patients with amyotrophic lateral sclerosis (ALS). We investigated whether VBM could identify cortical atrophy from T1-weighted images obtained during routine 1.5T studies of ALS patients with various clinically defined phenotypes. For this purpose T1-weighted brain MRI was obtained at 1.5T during routine clinical study in neurologic disease controls (n = 15) and ALS patients (n = 88) categorized into four subgroups based on their clinical phenotypes: predominant upper motor neuron (UMN) dysfunction with or without corticospinal tract (CST) hyperintensity (ALS-CST+/-), combined UMN and prominent lower motor neuron (LMN) dysfunction (classic ALS), and frontotemporal dementia (ALS-FTD). VBM analysis of gray matter (GM) was carried out using FSL. Results demonstrated that clinically obtained brain MRI at 1.5T revealed significantly reduced GM volume in brains of only ALS-FTD patients and not of those with predominant UMN dysfunction or classic ALS, compared to neurologic disease controls. In conclusion, GM volume loss in motor and extramotor regions of only ALS patients with FTD and not of ALS patients without FTD suggests distinct sites of predominant pathology and possibly of disease onset. Brain volumetric measures supplemented by histopathological correlations and other neuroimaging techniques, such as diffusion tensor imaging, may provide insight into ALS pathophysiology.
Keywords: ALS patients; FSL; gray matter; voxel based morphometry.