Sodium MRI of T1 High Signal Intensity in the Dentate Nucleus due to Gadolinium Deposition in Multiple Sclerosis

Eisele, Philipp; Konstandin, Simon; Szabo, Kristina; Ong, Melissa; Zöllner, Frank G.; Schad, Lothar R.; Schoenberg, Stefan O.; Gass, Achim

doi:10.1111/jon.12448

Cited by 26 publications

(17 citation statements)

References 17 publications

(42 reference statements)

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“…In contrast to previous studies, we did not find any indication of a washout of Gd deposits neither over time [25,26] nor when linear GBCA were followed by cyclic GBCA [13,14,29,30]. Alternatively, Gd washout may follow kinetics not detectable by our study, in which relatively homogenous intervals (about 11 months) were analyzed.…”

Section: Discussioncontrasting

confidence: 99%

“…Maximum intensity projection indicates that no further area was identified (c) sue damage, in MS patients. Within areas of increased T1w signal intensities of the DN, a normal sodium signal was determined and, hence, no evidence of GBCA-related tissue damage provided [30]. In addition, there may be kinetic aspects to be considered for the evaluation of MS patients with respect to Gd deposition.…”

Section: Discussionmentioning

confidence: 99%

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T1-Weighted Intensity Increase After a Single Administration of a Linear Gadolinium-Based Contrast Agent in Multiple Sclerosis

et al. 2020

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Purpose Through analysis of T1-weighted (T1w) images this study investigated gadolinium (Gd) deposition in the brain after administration of a linear (gadopentetic acid) and a cyclic (gadoteric acid) gadolinium-based contrast agent (GBCA) in patients with multiple sclerosis (MS), a disorder frequently requiring magnetic resonance imaging (MRI) scans over years. Methods A total of 3233 T1w images (unenhanced with respect to the same scanning session) of 881 MS patients were retrospectively analyzed. After spatial normalization and intensity scaling using a sphere within the pons, differences of all pairs of subsequent scans were calculated and attributed to either linear (n = 2718) or cyclic (n = 385) or no GBCA (n = 130) according to the first scan. Regional analyses were performed, focusing on the dentate nucleus, and whole brain analyses. By 1-sample t-tests, signal intensity increases within conditions were searched for; conditions were compared by 2-sample t-tests. Furthermore, recent hypotheses on the reversibility of GBCA deposition were tested. Results In the dentate nucleus, a significant increase was observed only after administration of linear GBCA even after a single GBCA administration. This increase differed significantly (p < 0.001) from the other conditions (cyclic and no GBCA). Whole brain analyses revealed T1w signal increases only after administration of linear GBCA within two regions, the dentate nucleus and globus pallidus. Additional analyses did not indicate any decline of Gd deposition in the brain. Conclusion The data point towards Gd deposition in the brain after administration of linear GBCA even after a single administration.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

T1-Weighted Intensity Increase After a Single Administration of a Linear Gadolinium-Based Contrast Agent in Multiple Sclerosis

et al. 2020

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“…Concerns over NSF and, more recently, Gd retention have led to a widespread migration from linear GBCAs to macrocyclic GBCAs for routine clinical use. Although studies to date suggest that GBCA exposure has no long‐term detrimental effects on human health either in terms of direct impact on tissue integrity, or global clinical disability, the possibility of long‐term effects is nevertheless a major area of current concern . Although assessment of potential long‐term safety issues was beyond the scope of this observational study, it is worth noting that all studies thus far performed in animals to evaluate Gd retention in brain and body tissues following GBCA exposure have shown that gadoteridol is retained to a lesser extent and cleared more rapidly than other GBCAs, including other macrocyclic GBCAs .…”

Section: Discussionmentioning

confidence: 99%

Prospective Multicenter Study of the Safety of Gadoteridol in 6163 Patients

Cho

Lee

Chang

et al. 2019

Magnetic Resonance Imaging

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Background: The safety of gadolinium-based contrast agents is of fundamental importance. Purpose: To determine the frequency and severity of immediate-type adverse reactions to approved doses of gadoteridol in patients referred for routine gadoteridol-enhanced MRI in actual clinical practice settings. Study Type: Prospective, observational. Population: In all, 6163 subjects were enrolled (mean age: 56.7 AE 15.4 years; range: 6-93 years). Field Strength/Sequence: 1.5T and 3.0T. Assessment: Assessment was of immediate adverse reactions by the investigating radiologist using the MedDRA System Organ Class and preferred term. Statistical Tests: Summary statistics for continuous variables, descriptive statistics for demographic characteristics. Results: Overall, 19 adverse events occurred in 13 (0.21%) patients, of which 15 in 10 (0.16%) patients were considered related to gadoteridol administration. These events were evenly distributed between male and female subjects and all occurred in adults. Twelve of the 15 related events in eight (0.13%) patients were considered mild in intensity (rapidly selfresolving), while the remaining three events in two patients (0.03%) were considered moderate in intensity. None were of severe intensity and no serious adverse events occurred. Data Conclusion: The rate of immediate-type adverse events following exposure to approved doses of gadoteridol is extremely low, and mostly limited to transient and self-resolving symptoms. Level of Evidence: 2 Technical Efficacy Stage: 5This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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“…25 These studies failed to demonstrate an association of brain gadolinium deposition with worsening of neurologic or neuropsychological status. 24,25 Also, studies applying imaging techniques to evaluate brain microstructural and functional integrity, such as sodium MR imaging, 26 resting-state functional MR imaging connectivity, 27 and http://dx.doi.org/10.3174/ajnr.A6586…”

Section: Brain Gadolinium Depositionmentioning

confidence: 99%

Gadolinium Deposition Safety: Seeking the Patient’s Perspective

Mallio¹,

Quattrocchi²,

Parizel³

2020

AJNR Am J Neuroradiol

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G adolinium is a rare-earth metal of the lanthanide series; it is represented by the symbol Gd, and its atomic number is 64. 1,2 At room temperature, Gd is paramagnetic, meaning that it enhances nuclear relaxation rates, making it useful as a contrast agent for MR imaging. In clinical practice, Gd ions are administered to patients in the chelated form as gadolinium-based contrast agents (GBCA). 1,2 GBCA were first introduced in the late 1980s. Because of the intrinsic toxicity of Gd salts, initial clinical trials focused on the stability of the complex between the Gd ion and the chelating agent. Early studies pointed out that the stability constant was much higher for macrocyclic (or cryptelates, as they were initially called) than for linear agents. 1,3 These concerns never received much attention because all linear and macrocyclic agents appeared to be safe and well-tolerated. Moreover, because macrocyclic GBCA were only available in Europe and not in North America, there appeared to be little scientific incentive to study these concerns further. In fact, GBCA were considered so safe that they were used in large volumes as intra-arterial contrast agents for conventional angiography in patients with iodine allergy. 4 Indeed, double-dose GBCA were also commonly applied for gadolinium-enhanced MR angiography studies. These practices all changed in 2006, when a possible causation was identified between GBCA and nephrogenic systemic fibrosis (NSF). 5 NSF is characterized by fibrosis of the skin and internal organs, and the symptoms are somewhat reminiscent of scleroderma or scleromyxedema, though the underlying pathology is different. In this respect, credit should be given to Cowper et al 6 for a very early and brilliant description of NSF. The first cases of NSF had already been described earlier, but the possible causation between NSF and GBCA in patients with renal insufficiency was first reported in 2006. 5 Next, in 2006, the FDA restricted the use of GBCA in patients with a glomerular filtration rate of ,60 mL and ,15 mL/ min/1.73 m 2 ; 7 the cutoff then proposed in 2007 was ,30 mL/ min/1.72 m 2. Due to these measures, NSF has become very rare, and GBCA were, once again, considered very safe agents in patients with normal renal function.

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Sodium MRI of T1 High Signal Intensity in the Dentate Nucleus due to Gadolinium Deposition in Multiple Sclerosis

Abstract: Normal sodium signal in the T1-hyperintense DN in MS patients may point to relative tissue integrity despite gadolinium deposition in this area.

Cited by 26 publications

References 17 publications

T1-Weighted Intensity Increase After a Single Administration of a Linear Gadolinium-Based Contrast Agent in Multiple Sclerosis

T1-Weighted Intensity Increase After a Single Administration of a Linear Gadolinium-Based Contrast Agent in Multiple Sclerosis

Prospective Multicenter Study of the Safety of Gadoteridol in 6163 Patients

Gadolinium Deposition Safety: Seeking the Patient’s Perspective

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