Abstract
ObjectivesTo 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 methodsOne 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.ResultsVisible 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).ConclusionMultiple injections of gadobutrol and/or gadoterate can lead to visible and quantifiable increases in DN/P SI ratio in some patients with MS.
Highlights
High signal intensity (SI) in the dentate nucleus (DN) and globus pallidus (GP) on unenhanced T1-weighted MR images following the cumulative administration of exclusivelySplendiani et al Insights into Imaging (2019) 10:82 macrocyclic gadolinium-based contrast agents (GBCAs) is currently a source of debate and controversy
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)
The widely held view is that visible T1-hyperintensity occurs primarily after the cumulative administration of so-called linear GBCAs rather than macrocyclic GBCAs and that the observed high T1-signal possibly reflects the release of gadolinium (Gd) from the linear chelating molecule and its subsequent retention in the brain, possibly through binding to cellular macromolecules [1,2,3,4,5,6]
Summary
High signal intensity (SI) in the dentate nucleus (DN) and globus pallidus (GP) on unenhanced T1-weighted MR images following the cumulative administration of exclusivelySplendiani et al Insights into Imaging (2019) 10:82 macrocyclic gadolinium-based contrast agents (GBCAs) is currently a source of debate and controversy. Numerous studies have demonstrated T1-signal increases in the brain after the exclusive administration of macrocyclic GBCAs [13,14,15,16,17,18,19] These studies have been criticized and marginalized, often by the manufacturers of the GBCA in question [20,21,22,23], in part, because the images presented do not show obvious T1-hyperintensity of the DN or GP to the extent seen with linear GBCAs [20]. Such criticism overlooks the fact that brain Gd retention has unequivocally been demonstrated in myriad animal studies [24,25,26,27,28,29,30,31] and in human brain autopsy samples after the exclusive administration of macrocyclic GBCAs [32]
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