Gray Matter Nucleus Hyperintensity After Monthly Triple-Dose Gadopentetate Dimeglumine With Long-term Magnetic Resonance Imaging

Abstract

Objectives Gadolinium deposition is widely believed to occur, but questions regarding accumulation pattern and permanence remain. We conducted a retrospective study of intracranial signal changes on monthly triple-dose contrast-enhanced magnetic resonance imaging (MRI) examinations from the previously published Betaseron vs. Copaxone in Multiple Sclerosis With Triple-Dose Gadolinium and 3-Tesla MRI Endpoints Trial (N = 67) to characterize the dynamics of gadolinium deposition in several deep brain nuclei and track persistence versus washout of gadolinium deposition on long-term follow-up (LTFU) examinations (N = 28) obtained approximately 10 years after enrollment in the Betaseron vs. Copaxone in Multiple Sclerosis With Triple-Dose Gadolinium and 3-Tesla MRI Endpoints Trial. Materials and Methods Using T2 and proton density images and using image analysis software (ITK-SNAP), manual regions of interest were created ascribing boundaries of the caudate nucleus, dentate nucleus, globus pallidus, pulvinar, putamen, white matter, and air. Intensity analysis was conducted on T1-weighted fat-saturated (fat-sat) images using the FSL package. A linear rigid-body transform was calculated from the fat-sat image at each target time point to the region of interest segmentation reference time point fat-sat image. Serial MRI signal was analyzed using linear mixed regression modeling with random intercept. Annual MRI signal changes including LTFU scans were assessed with t test. Results During monthly scanning, all gray matter structures demonstrated a significant (P < 0.0001) increase in contrast-to-noise ratio. Yearly changes in deposition showed distinctive patterns for the specific nucleus: globus pallidus showed complete retention, pulvinar showed partial washout, while dentate, caudate, and putamen returned to baseline (ie, complete washout). Conclusions Monthly increased contrast-to-noise ratio in gray matter nuclei is consistent with gadolinium deposition over time. The study also suggests that some deep gray matter nuclei permanently retain gadolinium, whereas others demonstrate washout of soluble gadolinium.

Can Deep Learning Replace Gadolinium in Neuro-Oncology?

“…For more than 30 years, GBCAs have been widely considered to be among the safest drugs ever introduced (2). However, since the identification of the role of gadolinium in nephrogenic systemic fibrosis (3,4) and the observation of its deposition in the brain (5), numerous studies have evaluated the cumulative effects of GBCA injections (6)(7)(8)(9)(10). Linear GBCAs have been shown to accumulate in the nucleus dentatus and globus pallidus, unlike macrocyclic agents which are more stable chemically (11,12).…”

Rare Earth Metallosis: Gadolinium-rich Nanoparticle Formation from Magnetic Resonance Imaging Contrast Agents in Rodent and Human Kidney

“…MRI contrast agent use in humans leads to detectable gadolinium in the kidney. In humans, permanent brain gadolinium retention may occur from the routine use of MRI contrast agents [25]. The kidney is a reservoir for gadolinium in rodent models [15,17,20,21,26].…”

Gadolinium Deposition Disease: A Case Report and the Prevalence of Enhanced MRI Procedures Within the Veterans Health Administration

“…Nonetheless, Gd is retained long-term in subjects with normal renal function, in symptomatic patients, permanently in the brains of patients, and in every organ we have tested with our animal models. 3,7,8,[10][11][12] Patients with normal renal function continue to report symptoms attributed to Gdbased contrast agents concomitant with retarded elimination. Numerous patients with normal renal function developed similar or novel symptoms that have been attributed to Gd concomitant with detectable urinary Gd years after exposure.…”