Our objective was to explore the value of additional MR contrasts in elucidating the decrease in fractional anisotropy (FA) as has been observed in the corticospinal tracts (CST) of patients with amyotrophic lateral sclerosis (ALS). Eleven patients and nine healthy control subjects were scanned at 3T and 7T MRI. Whole brain and tract specific comparison was performed of both diffusion weighted (3T), quantitative T1 (qT1), magnetization transfer ratio (MTR) and amide proton transfer weighted (APTw) imaging (7T). Results of whole brain comparison using histogram analyses showed no significant differences between patients and controls. Measures along the CST showed a significantly reduced FA together with a significantly increased diffusivity perpendicular to the tract direction in patients compared to controls. In addition, patients showed a small but significant increase in MTR values within the right CST. No significant changes were observed in qT1 and APTw values. In conclusion, our findings, based on a multimodal approach, revealed that the decrease in FA is most probably caused by an increased diffusivity perpendicular to the CST. This diffusivity profile, together with the increase in MTR is inconsistent with demyelination but consistent with an increase of free liquid spins in the white matter tissue.