With this study we investigated whether spinal cord gray and white matter atrophy could be detected in vivo in patients with a diagnosis within the motor neuron disease spectrum using PSIR imaging. Gray and white matter were successfully delineated in ten patients. Gray and white matter atrophy was detected in the majority of patients even if the lower or upper motor neuron was clinically unaffected. Patients with predominantly bulbar symptoms did not show relevant spinal cord abnormalities. This suggests a possible role of PSIR imaging as a biomarker for the spatial and temporal distribution of pathological changes in motor neuron disease.