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COVER ILLUSTRATION Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with highly heterogenous progression patterns. Presented are DTI contrasts of increased radial diffusivity for patients with ALS, that demonstrated a widespread white matter pathology if compared to healthy controls (top left). In Steinbach et al. the D50 disease progression model was applied which provides mathematically defined descriptors of the different progression types. It was used to quantify measures of disease covered independent from those of disease aggressiveness. Higher aggressiveness of patients' individual ALS disease was associated with elevated radial diffusivity in association tracts (top right). A positive correlation was found with the amount of disease covered (bottom left) as well as the calculated functional state (bottom right) at the day of MRI, representing individual disease accumulation early in disease. Harmonizing disease quantification by modelling thus greatly increased the sensitivity to identify ALS related brain disease.