Absence of dentate nucleus resting‐state functional connectivity changes in nonneurological patients with gadolinium‐related hyperintensity on T₁‐weighted images

Abstract

Background The dentate nuclei of the cerebellum are the areas where gadolinium predominantly accumulates. It is not yet known whether gadolinium deposition affects brain functions. Purpose/Hypothesis To assess whether gadolinium‐dependent high signal intensity of the cerebellum on T1‐weighted images of nonneurological adult patients with Crohn's disease is associated with modifications of resting‐state functional connectivity (RSFC) of the cerebellum and dentate nucleus. Study Type Observational, cross‐sectional. Population Fifteen patients affected by Crohn's disease were compared with 16 healthy age‐ and gender‐matched control subjects. All participants underwent neurological, neurocognitive‐psychological assessment, and blood sampling. Field Strength/Sequence 1.5‐T magnet blood oxygenation level‐dependent (BOLD) functional MRI. Assessment High signal intensity on T1‐weighted images, cerebellum functional connectivity, neurocognitive performance, and blood circulating gadolinium levels. Statistical Tests An unpaired two‐sample t‐test (age and sex were nuisance variables) was used to investigate between‐group differences in cerebellar and dentate nucleus functional connectivity. Z‐statistical images were set using clusters determined by Z > 2.3 and a familywise error (FWE)‐corrected cluster significance threshold of P = 0.05. Results Dentate nuclei RSFC was not different (P = n.s.) between patients with gadolinium‐dependent high signal intensity on T1‐weighted images and controls. Pre‐ and postcentral gyrus bilaterally and the right supplementary motor cortex showed a decrease of RSFC with the cerebellum hemispheres (P < 0.05 FWE‐corrected) and was related to disease duration but not to gadodiamide cumulative doses (P = n.s.). Data Conclusion Crohn's disease patients with gadolinium‐dependent hyperintense dentate nuclei on unenhanced T1‐weighted images do not show dentate nucleus RSFC changes. Level of Evidence: 2 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2019;50:445–455.

Prospective Multicenter Study of the Safety of Gadoteridol in 6163 Patients

“…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 .…”

Effect of Exposure to Gadodiamide and Brain Irradiation on T1‐Weighted Images and ADC Maps of the Dentate Nucleus

“…Despite the absence of changes in ADC values between patients exposed to brain irradiation and the control group, we observed a relationship between higher ADC values and shorter time after WBRT. From a biological standpoint, this finding might reflect early and subtle posttreatment vasogenic edema with weakening of the blood–brain barrier, possibly explaining the previously reported effects of radiation therapy on T 1 DN‐to‐pons ratios in patients exposed to GBCAs 13,14,21 . Indeed, a recent study based on a murine model with analysis of DWI and MRI dynamic contrast‐enhanced imaging, before and 24 hours after three daily fractions of 4 Gy whole‐brain radiotherapy, showed increased ADC values together with higher permeability (parameter K trans ) in the treated metastatic tumors 30 .…”

Analysis of retention of gadolinium by brain, bone, and blood following linear gadolinium‐based contrast agent administration in rats with experimental sepsis

“…This has been challenged by observations that unenhanced T 1 signal intensity increases with normal myelination as children mature, and by underlying pathological processes, which may complicate the interpretation of increasing unenhanced T 1 signal intensity as indicative of Gd deposition in patients who undergo multiple MRI examinations over time . No adverse clinical or pathological consequences of Gd deposition in the brain have thus far been confirmed . However, precautionary recommendations have been made in the use of linear GBCA by professional organizations and the Food and Drug Administration .…”

“…This has led to a new concern that linear GBCA, which undergoes dechelation, results in Gd deposition in many tissues, including the brain and bone. The significance of this concern has been challenged by the broad radiology community and lack of current clinical evidence of deleterious effects . However, linear GBCA have been largely withdrawn in Europe in favor of macrocyclic agents, which do not undergo dechelation .…”