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The aim of this study was to explore potential biomarkers for ALS by conducting postmortem (PM) in\u00a0situ MRI, allowing for a non\u2010invasive evaluation of the disease's end\u2010stage without the effects of formalin fixation. PM in\u00a0situ MRI whole\u2010brain scans of five deceased patients with clinically definite ALS and seven deceased healthy controls (HC) without known neurological disorders were performed at 3 Tesla. Fractional anisotropy, mean diffusivity, <jats:italic>T<\/jats:italic><jats:sub>1<\/jats:sub>, <jats:italic>T<\/jats:italic><jats:sub>2<\/jats:sub> and <jats:italic>T<\/jats:italic><jats:sub>2<\/jats:sub>* were assessed for cortex, deep grey matter, white matter, whole brain and hippocampus. For the validation of the MRI DTI data, the focus was placed on the hippocampus, where the myelin density was evaluated by analysing histological samples from the dentate gyrus. A custom python script was developed for the quantification of the myelin density in histological data. Comparing ALS to HC values suggested potential reductions of mean diffusivity, <jats:italic>T<\/jats:italic><jats:sub>1<\/jats:sub> (after outlier removal) and <jats:italic>T<\/jats:italic><jats:sub>2<\/jats:sub>* in white matter and of <jats:italic>T<\/jats:italic><jats:sub>2<\/jats:sub> in deep grey matter in the ALS group. Furthermore, mean diffusivity was potentially reduced in the hippocampus of patients with ALS (after outlier removal), whereas no difference in myelin density was found by histopathological assessment. The results of this exploratory study suggest potential differences in diffusivity and relaxometry between PM in\u00a0situ brains of patients with ALS and HC. Understanding these variations at the end\u2010stage of ALS might contribute to the development of novel MRI prognostic and diagnostic biomarkers for ALS. 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