Progressive Increase of T1 Signal Intensity of the Dentate Nucleus on Unenhanced Magnetic Resonance Images Is Associated With Cumulative Doses of Intravenously Administered Gadodiamide in Patients With Normal Renal Function, Suggesting Dechelation

Abstract

Our study shows that the increase in the unenhanced T1 signal intensity has a linear relationship with the eMRIn in patients with MS and BM. Indeed, we estimated a linear regression model to fit the progressive increase in T1 signal intensity of the dentate nucleus after multiple enhanced MRI scans. This finding suggests substantial dechelation of gadodiamide in patients with normal renal function, raising further concerns regarding the stability of this agent. Further comparative studies with other gadolinium chelates, specifically both linear and macrocyclic, are strongly recommended.

Gadolinium toxicity and treatment

“…Gadolinium presence was originally observed in bone [5,6,30] and more recently in the brain [7][8][9][31][32][33][34][35][36][37][38][39] in patients with normal renal function.…”

Contribution of metals to brain MR signal intensity: review articles

“…The administered gadolinium remains in the human body for a long time and causes abnormal signal intensity on T1WI (Fig. 4) [106][107][108]. Because of the toxicity of gadolinium, residual gadolinium has been attracting increasing attention [109][110][111][112][113][114][115][116].…”

Technical aspects of MRI signal change quantification after gadolinium-based contrast agents' administration

“…Different ratios have been used for quantitative measurements including DN-to-pons, DN-to-middle cerebellar peduncle, DN-to-cerebellar white matter, DN-to-CSF, DN-to-corpus callosum genu (CC), GP-to-Th, GP-to-CSF, GP-to-CC, Th-to-CC, and Caudate nucleus-to-CC [1][2][3][4][5][6][7][8][9][17][18][19][20]. In a study with healthy volunteers, T1 SI of DN, pons, GP, white matter, and gray matter were all evaluated and normalized with CSF [21].…”

“…Some authors suggested that 6 or more contrast enhanced MRI were needed to evaluate T1 signal changes over time [1,2], while others evaluate the effect of only one high dose GBCA [21]. Provided that the number of doses were all accounted for, including brain and other contrast enhanced MRI, the critical factor is that only one GBCA should be evaluated for each patient to determine the potential for deposition of each agent.…”

“…In the past 2 years several magnetic imaging (MRI) studies reported high T1 signal intensity in the dentate nucleus (DN) and/or globus pallidi (GP) in patients with normal renal function after multiple administrations of gadolinium-based contrast agents (GBCAs) suggesting gadolinium deposition [1][2][3][4][5][6][7][8][9]. The agent most commonly implicated was gadodiamide (Omniscan ® ) a non-ionic linear agent, classified according to its stability as a weak agent [10], followed by gadopentetate dimeglumine (Magnevist ® ) and gadobenate dimeglumine (MultiHance ® ), both ionic linear agents, classified as agents with intermediate stability [10].…”