OBJECTIVES: To investigate the appearance of visible dentate nucleus (DN) T1-hyperintensity and quantify changes in DN/pons (DN/P) signal intensity (SI) ratio in MS patients after the exclusive administration of macrocyclic GBCAs. MATERIALS AND METHODS: One hundred forty-nine patients with confirmed MS were evaluated. Patients received at least two administrations of gadobutrol (n = 63), gadoterate (n = 57), or both (n = 29). Two experienced neuroradiologists in consensus evaluated unenhanced T1-weighted MR images from all examinations in each patient for evidence of visible DN hyperintensity. Thereafter, SI measurements were made in the left and right DN and pons on unenhanced T1-weighted images from the first and last scans. A two-sample t test compared the DN/P SI ratios for patients with and without visible T1-hyperintensity. RESULTS: Visible T1-hyperintensity was observed in 42/149 (28.2%) patients (19 after gadobutrol only, 15 after gadoterate only, 8 after both), typically at the 4th or 5th follow-up exam at 3-4 years after the initial examination. Significant increases in DN/P SI ratio from first to last examination were determined for patients with visible T1-hyperintensity (0.998 ± 0.002 to 1.153 ± 0.016, p < 0.0001 for gadobutrol; 1.003 ± 0.004 to 1.110 ± 0.014, p < 0.0001 for gadoterate; 1.004 ± 0.011 to 1.163 ± 0.032, p = 0.0004 for both) but not for patients without visible T1-hyperintensity (p > 0.05; all groups). CONCLUSION: Multiple injections of gadobutrol and/or gadoterate can lead to visible and quantifiable increases in DN/P SI ratio in some patients with MS.