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Background and Purpose: To develop and test a decision tree for predicting contrast enhancement quality and shape using precontrast magnetic resonance imaging (MRI) sequences in a large adult‐type diffuse glioma cohort. Methods: Preoperative MRI scans (development/optimization/test sets: n = 31/38/303, male = 17/22/189, mean age = 52/59/56.7 years, high‐grade glioma = 22/33/249) were retrospectively evaluated, including pre‐ and postcontrast T1‐weighted, T2‐weighted, fluid‐attenuated inversion recovery, and diffusion‐weighted imaging sequences. Enhancement prediction decision tree (EPDT) was developed using development and optimization sets, incorporating four imaging features: necrosis, diffusion restriction, T2 inhomogeneity, and nonenhancing tumor margins. EPDT accuracy was assessed on a test set by three raters of variable experience. True enhancement features (gold standard) were evaluated using pre‐ and postcontrast T1‐weighted images. Statistical analysis used confusion matrices, Cohen's/Fleiss' kappa, and Kendall's W. Significance threshold was p <.05. Results: Raters 1, 2, and 3 achieved overall accuracies of.86 (95% confidence interval [CI]:.81‐.90),.89 (95% CI:.85‐.92), and.92 (95% CI:.89‐.95), respectively, in predicting enhancement quality (marked, mild, or no enhancement). Regarding shape, defined as the thickness of enhancing margin (solid, rim, or no enhancement), accuracies were.84 (95% CI:.79‐.88),.88 (95% CI:.84‐.92), and.89 (95% CI:.85‐.92). Intrarater intergroup agreement comparing predicted and true enhancement features consistently reached substantial levels (≥.68 [95% CI:.61‐.75]). Interrater comparison showed at least moderate agreement (group: ≥.42 [95% CI:.36‐.48], pairwise: ≥.61 [95% CI:.50‐.72]). Among the imaging features in the EPDT, necrosis assessment displayed the highest intra‐ and interrater consistency (≥.80 [95% CI:.73‐.88]). Conclusion: The proposed EPDT has high accuracy in predicting enhancement patterns of gliomas irrespective of rater experience. [ABSTRACT FROM AUTHOR]

Background: Previous in vitro studies have described sub‐linear longitudinal and heightened transverse H2O relaxivities of gadolinium‐based contrast agents (GBCAs) in blood due to their extracellular nature. However, in vivo validation is lacking. Purpose: Validate theory describing blood behavior of R1 and R2* in an animal model. Study Type: Prospective, animal. Animal Model: Seven swine (54–65 kg). Field Strength/Sequence: 1.5 T; time‐resolved 3D spoiled gradient‐recalled echo (SPGR) and quantitative Look‐Locker and multi‐echo fast field echo sequences. Assessment: Seven swine were each injected three times with 0.1 mmol/kg intravenous doses of one of three GBCAs: gadoteridol, gadobutrol, and gadobenate dimeglumine. Injections were randomized for rate (1, 2, and 3 mL/s) and order, during which time‐resolved aortic 3D SPGR imaging was performed concurrently with aortic blood sampling via an indwelling catheter. Time‐varying [GBCA] was measured by mass spectrometry of sampled blood. Predicted signal intensity (SI) was determined from a model incorporating sub‐linear R1 and R2* effects (whole‐blood model) and simpler models incorporating linear R1, with and without R2* effects. Predicted SIs were compared to measured aortic SI. Statistical Tests: Linear correlation (coefficient of determination, R2) and mean errors were compared across the SI prediction models. Results: There was an excellent correlation between predicted and measured SI across all injections and swine when accounting for the non‐linear dependence of R1 and high blood R2* (regression slopes 0.91–1.04, R2 ≥ 0.91). Simplified models (linear R1 with and without R2* effects) showed poorer correlation (slopes 0.67–0.85 and 0.54–0.64 respectively, both R2 ≥ 0.89) and higher averaged mean absolute and mean square errors (128.4 and 177.4 vs. 42.0, respectively, and 5506 and 11,419 vs. 699, respectively). Data Conclusion: Incorporating sub‐linear R1 and high first‐pass R2* effects in arterial blood models allows accurate SPGR SI prediction in an in vivo animal model, and might be utilized when modeling MR blood SI. Level of Evidence: 1 Technical Efficacy: Stage 1 [ABSTRACT FROM AUTHOR]

Abstract Background Recent evidence suggests that the failure of the glymphatic system – the brain’s waste clearance system, which is active during sleep – plays a key role in the pathophysiology of Alzheimer’s Disease (AD). Glymphatic function can be investigated using serial MRIs after intrathecal gadobutrol injection. This technique can reveal the health of the glymphatic system, but has not yet been used in participants with cognitive impairment due to AD. Case report This report describes the sleep and gadobutrol tracer clearance patterns of four participants diagnosed with mild to moderate cognitive impairment with evidence of AD pathology (pathological levels of Ab and p-tau in cerebrospinal fluid). We performed polysomnography and MRI studies before tracer injection and MRI scans at 1.5-2 h, 5–6 h, and 48 h after injection. Despite participants reporting no sleep problems, polysomnography revealed that all participants had moderate to severe sleep disturbances, including reduced sleep efficiency during the study and obstructive sleep apnea. Severe side-effects related to tracer administration were observed, impeding the completion of the protocol in two participants. Participants who finished the protocol displayed delayed and persistent tracer enrichment in the cortex and white matter, even 48 h after injection. These outcomes have not been observed in previous studies in participants without AD. Conclusion The findings suggest that brains with sleep impairment and AD pathology have poor glymphatic function, and therefore cannot clear the contrast tracer efficiently. This is likely to have caused the severe side effects in our participants, that have not been reported in healthy individuals. Our results may therefore represent the only available data acquired with this technique in participants with AD pathology.

Objectives: To investigate gadolinium deposition in the liver and brain in a rat model with liver fibrosis (LF) after intravenous administration of gadoxetate disodium (GD) and the histological effects of gadolinium deposition in the liver and brain. Methods: Adult male Sprague–Dawley rats were randomly assigned to one of the three groups: 1) LF group received intraperitoneal injection of carbon tetrachloride (CCl4) for 9 weeks alone; 2) LF&GD group received CCl4 and intravenous administration of GD (for 5 consecutive days); 3) GD group received olive oil and GD. Seven days after the final injection of GD, the deep cerebellar nuclei (DCN) and liver were excised to determine gadolinium concentrations via inductively coupled plasma mass spectrometry, and histologic staining was performed. Bonferroni's post-hoc test and Wilcoxon rank sum test were used to compare the differences between the three groups. Results: The concentrations of retained gadolinium in the liver in the LF&GD group (2.18 ± 0.44 μg/g) were significantly greater compared to the LF group (0.02 ± 0.01 μg/g, P

Background: Recent evidence suggests that the failure of the glymphatic system – the brain's waste clearance system, which is active during sleep – plays a key role in the pathophysiology of Alzheimer's Disease (AD). Glymphatic function can be investigated using serial MRIs after intrathecal gadobutrol injection. This technique can reveal the health of the glymphatic system, but has not yet been used in participants with cognitive impairment due to AD. Case report: This report describes the sleep and gadobutrol tracer clearance patterns of four participants diagnosed with mild to moderate cognitive impairment with evidence of AD pathology (pathological levels of Ab and p-tau in cerebrospinal fluid). We performed polysomnography and MRI studies before tracer injection and MRI scans at 1.5-2 h, 5–6 h, and 48 h after injection. Despite participants reporting no sleep problems, polysomnography revealed that all participants had moderate to severe sleep disturbances, including reduced sleep efficiency during the study and obstructive sleep apnea. Severe side-effects related to tracer administration were observed, impeding the completion of the protocol in two participants. Participants who finished the protocol displayed delayed and persistent tracer enrichment in the cortex and white matter, even 48 h after injection. These outcomes have not been observed in previous studies in participants without AD. Conclusion: The findings suggest that brains with sleep impairment and AD pathology have poor glymphatic function, and therefore cannot clear the contrast tracer efficiently. This is likely to have caused the severe side effects in our participants, that have not been reported in healthy individuals. Our results may therefore represent the only available data acquired with this technique in participants with AD pathology. [ABSTRACT FROM AUTHOR]

A technique for quantifying regional blood–brain barrier (BBB) water exchange rates using contrast‐enhanced arterial spin labelling (CE‐ASL) is presented and evaluated in simulations and in vivo. The two‐compartment ASL model describes the water exchange rate from blood to tissue, kb, but to estimate kb in practice it is necessary to separate the intra‐ and extravascular signals. This is challenging in standard ASL data owing to the small difference in T1 values. Here, a gadolinium‐based contrast agent is used to increase this T1 difference and enable the signal components to be disentangled. The optimal post‐contrast blood T1 (T1,bpost) at 3 T was determined in a sensitivity analysis, and the accuracy and precision of the method quantified using Monte Carlo simulations. Proof‐of‐concept data were acquired in six healthy volunteers (five female, age range 24–46 years). The sensitivity analysis identified the optimal T1,bpost at 3 T as 0.8 s. Simulations showed that kb could be estimated in individual cortical regions with a relative error ϵ<1% and coefficient of variation CoV=30%; however, a high dependence on blood T1 was also observed. In volunteer data, mean parameter values in grey matter were: arterial transit time tA=1.15±0.49 s, cerebral blood flow f=58.0±14.3 mL blood/min/100 mL tissue and water exchange rate kb=2.32±2.49 s−1. CE‐ASL can provide regional BBB water exchange rate estimates; however, the clinical utility of the technique is dependent on the achievable accuracy of measured T1 values. [ABSTRACT FROM AUTHOR]

BACKGROUND: Neonates and young children require efficacious magnetic resonance imaging (MRI) examinations but are potentially more susceptible to the short- and long-term adverse effects of gadolinium-based contrast agents due to the immaturity of their body functions. OBJECTIVE: To evaluate the acute safety and diagnostic efficacy of gadoteridol (ProHance) for contrast-enhanced MRI of the central nervous system (CNS) in children ≤2 years of age. MATERIALS AND METHODS: One hundred twenty-five children ≤2 years old (including 57 children

Contrast agents have been used in magnetic resonance imaging (MRI) as a radiological method. Gadolinium‐based contrast agents (GBCAs), because of their paramagnetic characteristics, are the ones mostly used in MRI to increase signal intensity. However, the use of contrast media has raised concerns on cellular toxic risks of these agents. Studies showed the accumulation of gadolinium after injection to humans with or without renal impairment. Also, there are findings obtained under in vitro and/or in vivo conditions that revealed conflicting results for their cytotoxic and genotoxic effects. Some of them declared damage in cells and genetic material; some others did not. Abnormal cell growth and genetic aberration are critical because they may lead to carcinogenesis in somatic cells or may be transferred to the next generations through germ cells. Therefore, understanding the effect of GBCAs on cells is important for their safer usage in clinical administrations to generate high‐quality contrast‐enhanced magnetic resonance images. Because of all these reasons, cellular toxicities—mainly genotoxic and cytotoxic effects—of GBCAs were reviewed in this paper. Contrast agents have been used in magnetic resonance imaging (MRI) as a diagnostic method. Rapid growth of diagnostic imaging elevated using of gadolinium‐based contrast agents (GBCAs) used in MRI to increase signal intensity. However, the use of contrast media has raised concerns on cellular toxic risks of these agents because of the accumulation of gadolinium after injection to humans with or without renal impairment. Therefore, cellular toxicities—mainly genotoxic and cytotoxic effects—of GBCAs were reviewed in this paper for their safer usage. [ABSTRACT FROM AUTHOR]

Objective This is the first study to explore the risk factors for nephropathy caused by gadolinium-based contrast agents and establish a prediction model to identify high-risk patients.Methods A total of 1404 patients who received gadolinium-based contrast agents in our hospital were included. The participants were randomly assigned in a 7:3 ratio to the modeling and validation groups. The modeling group was divided into a contrast-induced nephropathy group and a non-contrast-induced nephropathy group. The clinical characteristics before the use of contrast agents were compared between the two groups. The risk factors for contrast-induced nephropathy were analyzed by logistic regression. A nomogram that could predict the incidence of contrast-induced nephropathy was plotted. The validation group was used to verify the predictive model.Results The incidence of contrast-induced nephropathy caused by gadolinium-based contrast agents was 3.92% (55/1404). The logistic stepwise regression analysis showed that sex, systolic pressure (SBP), absolute neutrophil count, albumin, fasting blood glucose level, and furosemide use were significant predictors of contrast-induced nephropathy caused by gadolinium-based contrast agents. The above predictors were then included in the nomogram construction. The area under the receiver operating characteristic (ROC) curve was 0.82 (p

Background and Purpose: The clinical correlation of gadolinium‐based contrast agents (GBCAs) has not been well studied in multiple sclerosis (MS). We investigated the extent to which the number of GBCA administrations relates to self‐reported disability and performance measures. Methods: A cohort of MS patients was analyzed in this retrospective observational study. The main outcome was the association between the cumulative number of GBCA exposures (linear or macrocyclic GBCA), Patient‐Determined Disease Steps (PDDS), and measures of physical and cognitive performance (walking speed test, manual dexterity test [MDT], and processing speed test [PST]). The analysis was performed first cross‐sectionally and then longitudinally. Results: The cross‐sectional data included 1059 MS patients with a mean age of 44.0 years (standard deviation = 11.2). While the contrast ratio in globus pallidus weakly correlated with PDDS, MDT, and PST in a univariate correlational analysis (coefficients, 95% confidence interval [CI] = 0.11 [0.04, 0.18], 0.15 [0.08, 0.21], and –0.16 [–0.10, –0.23], respectively), the associations disappeared after covariate adjustment. A significant association was found between number of linear GBCA administrations and PDDS (coefficient [CI] = –0.131 [–0.196, –0.067]), and MDT associated with macrocyclic GBCA administrations (–0.385 [–0.616, –0.154]), but their signs indicated better outcomes in patients with greater GBCA exposures. The longitudinal data showed no significant detrimental effect of macrocyclic GBCA exposures. Conclusion: No detrimental effects were observed between GBCA exposure and self‐reported disability and standardized objective measures of physical and cognitive performance. While several weak associations were found, they indicated benefit on these measures. [ABSTRACT FROM AUTHOR]

Combining magnetic resonance imaging (MRI) sequences that permit the determination of vestibular nerve angulation (NA = change of nerve caliber or direction), structural nerve integrity via diffusion tensor imaging (DTI), and exclusion of endolymphatic hydrops (ELH) via delayed gadolinium-enhanced MRI of the inner ear (iMRI) could increase the diagnostic accuracy in patients with vestibular paroxysmia (VP). Thirty-six participants were examined, 18 with VP (52.6 ± 18.1 years) and 18 age-matched with normal vestibulocochlear testing (NP 50.3 ± 16.5 years). This study investigated whether (i) NA, (ii) DTI changes, or (iii) ELH occur in VP, and (iv) to what extent said parameters relate. Methods included vestibulocochlear testing and MRI data analyses for neurovascular compression (NVC) and NA verification, DTI and ELS quantification. As a result, (i) NA increased NVC specificity. (ii) DTI structural integrity was reduced on the side affected by VP (p < 0.05). (iii) 61.1% VP showed mild ELH and higher asymmetry indices than NP (p > 0.05). (iv) "Disease duration" and "total number of attacks" correlated with the decreased structural integrity of the affected nerve in DTI (p < 0.001). NVC distance within the nerve's root-entry zone correlated with nerve function (Roh = 0.72, p < 0.001), nerve integrity loss (Roh = − 0.638, p < 0.001), and ELS volume (Roh = − 0.604, p < 0.001) in VP. In conclusion, this study is the first to link eighth cranial nerve function, microstructure, and ELS changes in VP to clinical features and increased vulnerability of NVC in the root-entry zone. Combined MRI with NVC or NA verification, DTI and ELS quantification increased the diagnostic accuracy at group-level but did not suffice to diagnose VP on a single-subject level due to individual variability and lack of diagnostic specificity. [ABSTRACT FROM AUTHOR]

Giving contrast material before 1H-magnetic resonance spectroscopy (MRS) could enhance the precision of locating the lesion of interest. However, evidence indicates that contrast material might influence the outcomes of MRS.To verify the effect of gadolinium-based contrast agent (GBCA) on MRS in normal white matter.A total of 34 patients were referred for brain magnetic resonance imaging (MRI) with GBCAs, and they underwent single-volume MRS before and after administering contrast material. Those patients had the MRS voxel placed at the right frontal normal white matter, which remained consistent across all examinations. Measurements were taken for the integral concerning N-acetyl aspartate (NAA), choline (Cho), creatine (Cr and Cr2), and myo-inositol (Ins) in all examinations.NAA (P = 0.0313) and Cho (P = 0.0094) had a significant decrease in their integral after intravenous GBCA administration. No significant differences were found between the pre- and post-contrast MRS studies for Cr, Cr2, and Ins.Intravenous GBCA can alter NAA and Cho integrals in normal white matter. Therefore, brain 1H-MRS should precede intravenous GBCA administration to avoid the potential impact of contrast material on peak integrals. [ABSTRACT FROM AUTHOR]

This is the first study to explore the risk factors for nephropathy caused by gadolinium-based contrast agents and establish a prediction model to identify high-risk patients. A total of 1404 patients who received gadolinium-based contrast agents in our hospital were included. The participants were randomly assigned in a 7:3 ratio to the modeling and validation groups. The modeling group was divided into a contrast-induced nephropathy group and a non-contrast-induced nephropathy group. The clinical characteristics before the use of contrast agents were compared between the two groups. The risk factors for contrast-induced nephropathy were analyzed by logistic regression. A nomogram that could predict the incidence of contrast-induced nephropathy was plotted. The validation group was used to verify the predictive model. The incidence of contrast-induced nephropathy caused by gadolinium-based contrast agents was 3.92% (55/1404). The logistic stepwise regression analysis showed that sex, systolic pressure (SBP), absolute neutrophil count, albumin, fasting blood glucose level, and furosemide use were significant predictors of contrast-induced nephropathy caused by gadolinium-based contrast agents. The above predictors were then included in the nomogram construction. The area under the receiver operating characteristic (ROC) curve was 0.82 (p < 0.001). The specificity and sensitivity corresponding to the optimal cutoff point (0.039) based on the area under the ROC curve were 71.9% and 80.5%, respectively. Sex, SBP, absolute neutrophil count, albumin, fasting blood glucose levels, and furosemide use are significant predictors of contrast-induced nephropathy caused by gadolinium-based contrast agents. Therefore, the incidence of contrast-induced nephropathy may be estimated by the prediction model established in this study before the use of contrast agents. [ABSTRACT FROM AUTHOR]

Background: Giving contrast material before 1 H-magnetic resonance spectroscopy (MRS) could enhance the precision of locating the lesion of interest. However, evidence indicates that contrast material might influence the outcomes of MRS., Purpose: To verify the effect of gadolinium-based contrast agent (GBCA) on MRS in normal white matter., Material and Methods: A total of 34 patients were referred for brain magnetic resonance imaging (MRI) with GBCAs, and they underwent single-volume MRS before and after administering contrast material. Those patients had the MRS voxel placed at the right frontal normal white matter, which remained consistent across all examinations. Measurements were taken for the integral concerning N-acetyl aspartate (NAA), choline (Cho), creatine (Cr and Cr2), and myo-inositol (Ins) in all examinations., Results: NAA ( P  = 0.0313) and Cho ( P  = 0.0094) had a significant decrease in their integral after intravenous GBCA administration. No significant differences were found between the pre- and post-contrast MRS studies for Cr, Cr2, and Ins., Conclusion: Intravenous GBCA can alter NAA and Cho integrals in normal white matter. Therefore, brain 1 H-MRS should precede intravenous GBCA administration to avoid the potential impact of contrast material on peak integrals., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The association of repeated administration of gadolinium‐based contrast agents (GBCAs) with the gadolinium (Gd) retention in the brains of mother and fetus remains unclear. Purpose: To investigate the effects of pregnancy and repeated administration of GBCAs on Gd retention in the brains of mother and pup mice. Study type: Cross‐sectional cohort toxicity study. Animal Model: From gestational days 16–19, pregnant (n = 48) BALB/c mice. Field Strength: A 9.4 T and fast spin echo sequence. Assessment: Half of the mother mice (n = 24) were killed at postnatal day 1 (P1) for inductively coupled plasma mass spectrometry (ICP‐MS) and transmission electron microscopy (TEM). Besides the ICP‐MS and TEM, four pups were randomly selected from each mother and killed at P1 for ultraperformance liquid chromatography mass spectrometry (UPLC‐MS) and Nissl staining. Statistical Tests: One‐way analysis of variance and unpaired t‐test. Results: In the group of gadodiamide, retention of Gd in the brains of pregnant mice was significantly lower than that of nonpregnant mice in the area of the deep cerebellar nuclei (DCN) (10.35 ± 2.16 nmol/g vs. 18.74 ± 3.65 nmol/g). Retention of Gd in the DCN of pups whose mothers were administered gadoterate meglumine was significantly lower than that of pups whose mothers were administered gadodiamide (0.21 ± 0.09 nmol/g vs. 6.15 ± 3.21 nmol/g) at P1. In mice treated with gadodiamide, most of the retained Gd in the brain tissue was insoluble (19.5% ± 9.5% of the recovered amount corresponded to the intact complex in the DCN). Data Conclusion: In different brain areas of the mother and pup mice, the retention of Gd after gadoterate meglumine administration was lower than that of gadodiamide and gadopentetate dimeglumine administration, and almost all the detected Gd in pups' brains was intact soluble GBCAs. Evidence Level: 1 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Purpose: Several studies reported gadolinium deposition in the dentate nuclei (DN) and the globus pallidus (GP) that was associated to linear GBCA administrations rather than macrocyclic. It is therefore imperative to evaluate and assess the safety of cumulative administration of gadoterate meglumine (macrocyclic). Thus, T1-weighted images (T1WI) of multiple sclerosis (MS) patients longitudinally followed for 4 years were retrospectively analyzed. Methods: In this study 44 patients, 10 with clinically isolated syndrome (CIS), 24 relapsing-remitting MS (RRMS) and 10 primary-progressive MS (PPMS) were examined every 6 months (first four scans) and then with a 1-year interval (last two scans). Image processing consisted in reorienting unenhanced T1WI to standard space, followed by B1 inhomogeneity correction. A patient-specific template was then generated to normalize T1WI signal intensity (SI) and segment the DN and subcortical GM structures. All structures were then transformed to each patient space in order to measure the SI in each region. The cerebellar peduncles (CP) and semi-oval (SO) white matter were then manually delineated and used as reference to calculate SI ratios in the DN and subcortical GM structures. A linear mixed-effect model was finally applied to longitudinally analyze SI variations. Results: The SI measurements performed in all structures showed no significant increases with the cumulative GBCA administration. Conclusion: This study showed no significant SI increases within the DN and subcortical GM structures of longitudinally followed MS patients even with the cumulative administration of the macrocyclic GBCA gadoterate meglumine. [ABSTRACT FROM AUTHOR]

Purpose: Simultaneous PET/MR imaging involves injection of a radiopharmaceutical and often also includes administration of a gadolinium‐based contrast agent (GBCA). Phantom model studies indicate that attenuation of annihilation photons by GBCAs does not bias quantification metrics of PET radiopharmaceutical uptake. However, a direct comparison of attenuation‐corrected PET values before and after administration of GBCA has not been performed in patients imaged with simultaneous dynamic PET/MR. The purpose of this study was to investigate the attenuating effect of GBCAs on standardized uptake value (SUV) quantification of 18F‐fluorodeoxyglucose (FDG) uptake in invasive breast cancer and normal tissues using simultaneous PET/MR. Methods: The study included 13 women with newly diagnosed invasive breast cancer imaged using simultaneous dedicated prone breast PET/MR with FDG. PET data collection and two‐point Dixon‐based MR attenuation correction sequences began simultaneously before the administration of GBCA to avoid a potential impact of GBCA on the attenuation correction map. A standard clinical dose of GBCA was intravenously administered for the dynamic contrast enhanced MR sequences obtained during the simultaneous PET data acquisition. PET data were dynamically reconstructed into 60 frames of 30 s each. Three timing windows were chosen consisting of a single frame (30 s), two frames (60 s), or four frames (120 s) immediately before and after contrast administration. SUVmax and SUVmean of the biopsy‐proven breast malignancy, fibroglandular tissue of the contralateral normal breast, descending aorta, and liver were calculated prior to and following GBCA administration. Percent change in the SUV metrics were calculated to test for a statistically significant, non‐zero percent change using Wilcoxon signed‐rank tests. Results: No statistical change in SUVmax or SUVmean was found for the breast malignancies or normal anatomical regions during the timing windows before and after GBCA administration. Conclusions: GBCAs do not significantly impact the results of PET quantification by means of additional attenuation. However, GBCAs may still affect quantification by affecting MR acquisitions used for MR‐based attenuation correction which this study did not address. Corrections to account for attenuation due to clinical concentrations of GBCAs are not necessary in simultaneous PET/MR examinations when MR‐based attenuation correction sequences are performed prior to GBCA administration. [ABSTRACT FROM AUTHOR]

Background: An association between consecutive administrations of macrocyclic gadolinium-based contrast agent (mcGBCA) gadobutrol and linear (L)-GBCA gadopentetate dimeglumine and gadolinium retention in the pediatric brain remains incompletely understood. Purpose: To compare signal intensity (SI) changes in the dentate nucleus (DN) on unenhanced T1-weighted imaging (T1WI) in children who obtained mcGBCA gadobutrol with those who had previously received L-GBCA gadopentetate dimeglumine. Material and Methods: This retrospective study included 27 children who received L-GBCA gadopentetate dimeglumine followed by mcGBCA gadobutrol and two different control groups matched for age and sex for both periods, each involving 27 individuals with no GBCA administration from January 2010 to January 2020. DN-to-middle cerebellar peduncle (MCP) SI ratios on T1WI were determined. A repeated-measures ANOVA was performed to compare the T1WI SI ratio between children exposed to GBCA in each of the two periods and controls. Pearson correlation analysis was conducted to determine any correlation between SI ratios and confounding parameters. Results: T1WI SI ratio was significantly higher in those who had only L-GBCA (1.005±0.087) or subsequent mcGBCA gadobutrol (1.002±0.104) than in control groups 1 (0.927±0.041; P <0.001) and 2 (0.930±0.041; P =0.002), respectively, but no significant difference of the T1WI SI ratio was noted between L-GBCA period and subsequent mcGBCA gadobutrol period (P =0.917). T1WI SI ratios and the L-GBCA administration number revealed a modest but significant correlation (correlation coefficient=0.034; P =0.016). Conclusion: Previous administration of gadopentetate dimeglumine is associated with increased T1WI SI in the DN, while subsequent administration of gadobutrol does not demonstrate any additional SI increase in the pediatric brain. [ABSTRACT FROM AUTHOR]

Gadolinium-based contrast agents (GBCAs) have transformed magnetic resonance imaging (MRI) by facilitating the use of contrast-enhanced MRI to allow vital clinical diagnosis in a plethora of disease that would otherwise remain undetected. Although over 500 million doses have been administered worldwide, scientific research has documented the retention of gadolinium in tissues, long after exposure, and the discovery of a GBCA-associated disease termed nephrogenic systemic fibrosis, found in patients with impaired renal function. An understanding of the pharmacokinetics in humans and animals alike are pivotal to the understanding of the distribution and excretion of gadolinium and GBCAs, and ultimately their potential retention. This has been well studied in humans and more so in animals, and recently there has been a particular focus on potential toxicities associated with multiple GBCA administration. The purpose of this review is to highlight what is currently known in the literature regarding the pharmacokinetics of gadolinium in humans and animals, and any toxicity associated with GBCA use. [ABSTRACT FROM AUTHOR]

POEMS syndrome is a rare paraneoplastic condition related to an abnormal proliferation of plasma cells. Allergic-type reactions to gadolinium-based MR contrast media are likewise uncommon adverse events. In this report, we present a highly unusual case involving the collision of these 2 entities. Because the reaction developed unrecognized during the course of the MR examination, the case provides not only a review of the major radiological manifestations of POEMS syndrome, but also a unique insight into the imaging features of an acute contrast reaction. We briefly discuss the incidence and classification of allergic-type contrast reactions and explore possible associations with hematologic dyscrasias.

Rationale and Objectives: Gadolinium deposition in the dentate nucleus (DN) has been evaluated by T1-weighted imaging (T1WI) and T1 (R1) mapping, but not MR fingerprinting (MRF). This study investigated associations between T1 and T2 values of DN and gadolinium-based contrast agents (GBCAs) using 2-dimensional MRF., Materials and Methods: This study included 101 patients. Region of interest analysis was performed for T1 and T2 values of DN on MRF (T1-MRF, T2-MRF) and T1-weighted images (T1WI ratio). T1 and T2 ratios compared to normal cerebellar white matter (T1-MRF ratio, T2-MRF ratio) were calculated. The type of previous GBCA was confirmed in 79 patients, and linear regressions were performed between T1, T2 values and number of GBCAs., Results: Good correlations were observed between T1-MRF and T1WI ratio (ρ = -0.69, P < 0.001) and between T1-MRF ratio and T1WI ratio (ρ = -0.76, P < 0.001). Mild correlations were observed between T2-MRF and T1WI ratio (ρ = -0.32, P < 0.001) and between T2-MRF ratio and T1WI ratio (ρ = -0.44, P < 0.001). The number of linear-type GBCAs was associated with T1-MRF (β = -0.62, P < 0.001) and T1-MRF ratio (β = -0.54, P < 0.001) in univariate linear regression analyses, and with T1-MRF (β = -0.61, P < 0.001) and T1-MRF ratio (β = -0.53, P < 0.001) in multivariate analysis. The number of linear-type GBCAs was associated with T2-MRF (β = -0.30, P < 0.001) and T2-MRF ratio (β = -0.29, P < 0.001) in univariate analyses, and with T2-MRF (β = -0.31, P < 0.001) and T2-MRF ratio (β = -0.32, P < 0.001) in multivariate analyses. No associations were observed between number of macrocyclic GBCAs and T1-MRF (ratio) or T2-MRF (ratio)., Conclusion: The number of linear-type GBCA administrations was associated with lower T1 and T2 values (ratios) in DN., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yasutaka Fushimi reports financial support was provided by JSPS Kakenhi JP21K15623, JP22K07746. Yuta Urushibata reports a relationship with Siemens Healthcare K. K., Japan. that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

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Gadolinium deposition has been reported in several normal anatomical structures in the brain after repeated administration of intravenous gadolinium-based contrast agents (GBCAs) used in magnetic resonance imaging (MRI). This study presents preliminary results to see if there is any gadolinium deposition in the dentate nucleus and globus pallidus after using intrathecal GBCAs. Between November 2018 and November 2020, 29 patients who underwent intrathecal contrast-enhanced MR cisternography with the suspicion of rhinorrhea were included in this prospective study. In contrast-enhanced MR cisternography, gadoterate meglumine was administered by intrathecal injection at a dose of 1 ml. One month later, patients had a control MRI with 3D T1 SPACE fat-saturated (FS) and susceptibility weighted images (SWI) sequences. The ratio of dentate nucleus signal intensity to middle cerebellar peduncle signal intensity (DN/MCP ratio) and the ratio of globus pallidus signal intensity to thalamus signal intensity (GP/T ratio) were calculated using region of interest (ROI) on pre-contrast and control MRI sequences. There was no significant difference for DN/MCP ratio and GP/T ratio on 3D T1 SPACE FS and SWI sequences after intrathecal GBCAs administration compared to baseline MRI. Administration of intrathecal GBCAs did not cause a measurable change in the signal intensity of the dentate nucleus and globus pallidus after a single injection. • Gadolinium deposition has been reported in several normal anatomical structures in the brain. • In contrast-enhanced MR cisternography, gadoterate meglumine was administered by intrathecal injection at a dose of 1 ml. • There was no significant difference on MRI after intrathecal GBCAs administration compared to baseline MRI. [ABSTRACT FROM AUTHOR]

Gadolinium-based contrast agents (GBCAs) have been used to improve image quality of MRI examinations for decades and have an excellent overall safety record. However, there are well-documented risks associated with GBCAs and our understanding and management of these risks continue to evolve. The purpose of this review is to discuss the safety of GBCAs used in MRI in adult and pediatric populations. We focus particular attention on acute adverse reactions, nephrogenic systemic fibrosis and gadolinium deposition. We also discuss the non-GBCA MRI contrast agent ferumoxytol, which is increasing in use and has its own risk profile. Finally, we identify special populations at higher risk of harm from GBCA administration. [ABSTRACT FROM AUTHOR]

Background: Gadolinium-based contrast agents (GBCAs) are widely used in magnetic resonance imaging (MRI). Recently, increased signal intensity has been reported in specific brain areas after repeated administrations of GBCAs. Purpose: To investigate the toxic effects of GBCAs on neuronal cells by using SH-SY5Y neuroblastoma cell cultures. Material and Methods: For toxicity assays, SH-SY5Y cells were incubated with different doses (0-1000 p.M) of several macrocyclic (gadoterate meglumine and gadobutrol) and linear GBCAs (gadoversetamide, gadopentetate dimeglumine, gadodiamide, and gadoxetate disodium) for 48 h. Cell viability and proliferation capacity were evaluated by using MTS assay, LDH assay, and colony-forming assay. In addition, Western blotting of Bcl-2 and Bax proteins and nuclear Hoechst 33258 staining were performed to evaluate apoptotic cell death. The results were expressed as mean ± SEM. The data were analyzed using Student's t-test. A P value < 0.05 was accepted as statistically significant. Results: Both macrocyclic and linear GBCAs significantly and dose-dependently reduced cell viability in neuronal cells compared to control. Cell viability was measured between 89.5% ±4% and 61% ±0.7% in GBCA-treated groups. In addition, neurotoxicity was more prominent in linear GBCA-treated cultures (P < 0.0005). Bax protein levels were increased in GBCA-treated cells particularly with linear agents whereas Bcl-2 expression was decreased concomitantly. Conclusion: The results of the present study indicated that exposure to specific GBCAs, even at low micro-molar concentrations, may have detrimental effects on neuronal survival. Further investigations are required to clarify the molecular mechanism underlying GBCA-induced cell death. [ABSTRACT FROM AUTHOR]

Over the past few years, a large number of studies have evidenced increased signal intensity in the deep brain nuclei on unenhanced T1-MRI images achieved by the application of gadolinium-based contrast agents (GBCAs). The deposition of gadolinium in the brain, bone, and other tissues following administration of GBCAs has also been confirmed in histological studies in rodents and in necropsy studies in adults and children. Given the distinct physiological characteristics of children, this review focuses on examining the current research on gadolinium deposition in children, particularly studies utilizing novel methods and technologies. Furthermore, the article compares safety research findings of linear GBCAs and macrocyclic GBCAs in children, with the aim of offering clinicians practical guidance based on the most recent research outcomes. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2., (© 2024 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Magnetic resonance imaging (MRI) with gadolinium based contrast agents (GBCA) is routinely used in the clinic to visualize lesions in multiple sclerosis (MS). Although GBCA reveal endothelial permeability, they fail to expose other aspects of lesion formation such as the magnitude of inflammation or tissue changes occurring at sites of blood-brain barrier (BBB) disruption. Moreover, evidence pointing to potential side effects of GBCA has been increasing. Thus, there is an urgent need to develop GBCA-independent imaging tools to monitor pathology in MS. Using MR-elastography (MRE), we previously demonstrated in both MS and the animal model experimental autoimmune encephalomyelitis (EAE) that inflammation was associated with a reduction of brain stiffness. Now, using the relapsing-remitting EAE model, we show that the cerebellum—a region with predominant inflammation in this model—is especially prone to loss of stiffness. We also demonstrate that, contrary to GBCA-MRI, reduction of brain stiffness correlates with clinical disability and is associated with enhanced expression of the extracellular matrix protein fibronectin (FN). Further, we show that FN is largely expressed by activated astrocytes at acute lesions, and reflects the magnitude of tissue remodeling at sites of BBB breakdown. Therefore, MRE could emerge as a safe tool suitable to monitor disease activity in MS.

Objective: To determine diagnostic confidence and inter-observer/intra-observer agreement in differentiating epidural fibrosis from disc herniation and lumbar spinal stenosis parameters on magnetic resonance images (MRI) in postoperative lumbar spines with (Gad-MRI) and without (unenhanced MRI) intravenous gadolinium-based contrast agent. Subjects and methods: N = 124 lumbar spine MRI examinations of four groups were included: 1–6 months, 7–18 months, 19–36 months, more than 37 months between lumbar spine surgery and imaging. Two radiologists evaluated Gad-MRI and unenhanced MRI: diagnostic confidence was determined as confident or unconfident. Inter-observer and intra-observer agreement were assessed in differentiating epidural fibrosis from disc herniation and for lumbar spinal stenosis parameters on MRI. Fisher's exact test and Cohen's kappa served for statistics. Results: Diagnostic confidence in differentiating epidural fibrosis from disc herniation was significantly higher on Gad-MR images compared with unenhanced MRI at 1–18 months for observer 1 and at 1–6 months postoperatively for observer 2 (p values: 0.01–0.025). Inter-observer agreement at 1–6 months postoperatively for identification of epidural fibrosis was higher on Gad-MRI (kappa values: 0.53 versus 0.24). Inter-observer and intra-observer agreement for identification of disc herniation and for assessment of lumbar spinal stenosis parameters revealed inconsistent data, without a trend for higher inter-observer or intra-observer agreement on Gad-MRI compared with unenhanced MRI (kappa values: 0.17–0.75). Conclusion: Gad-MR images compared with unenhanced MRI improved diagnostic confidence and agreement in differentiating epidural fibrosis from disc herniation for both observers in the first 6 months and for one observer in the first 18 months after lumbar spine surgery. After 18 months, Gad-MR images compared with unenhanced MRI did neither improve confidence nor agreement. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) patients represent a population potentially affected by the intracerebral accumulation of gadolinium-based contrast agents (GBCA) due to repeated magnetic resonance imaging (MRI) performed during their lifetime; however, MRI is still the best tool to monitor MS inflammatory activity. Objective: This study aimed to evaluate the relevance of GBCA injections during the MRI follow-up of MS patients under natalizumab (Tysabri) treatment. Methods: The MRI data results were retrospectively reviewed in a monocentric study (University Hospital of Toulouse, France) from all consecutive patients treated with natalizumab from January 2014 to January 2017. For each examination during the whole MRI follow-up, new lesions (enhancing and non-enhancing) were analyzed. Results: A total of 129 patients were included in this study (65% female, mean age = 41 years, mean treatment duration 6.5 years, 50% positive for John Cunningham virus) and benefited from 735 MRIs with GBCA. Only 3 MRIs showed a new enhancing lesion, systematically encountered after treatment discontinuation. Conclusion: According to this study based on the clinical and radiological practice, the systematic use of GBCA seems of limited relevance in the MRI follow-up of asymptomatic patients treated continuously with natalizumab. [ABSTRACT FROM AUTHOR]

Objectives: To investigate gadolinium deposition in the liver and brain in a rat model with liver fibrosis (LF) after intravenous administration of gadoxetate disodium (GD) and the histological effects of gadolinium deposition in the liver and brain., Methods: Adult male Sprague-Dawley rats were randomly assigned to one of the three groups: 1) LF group received intraperitoneal injection of carbon tetrachloride (CCl 4 ) for 9 weeks alone; 2) LF&GD group received CCl 4 and intravenous administration of GD (for 5 consecutive days); 3) GD group received olive oil and GD. Seven days after the final injection of GD, the deep cerebellar nuclei (DCN) and liver were excised to determine gadolinium concentrations via inductively coupled plasma mass spectrometry, and histologic staining was performed. Bonferroni's post-hoc test and Wilcoxon rank sum test were used to compare the differences between the three groups., Results: The concentrations of retained gadolinium in the liver in the LF&GD group (2.18 ± 0.44 μg/g) were significantly greater compared to the LF group (0.02 ± 0.01 μg/g, P  < 0.001) and GD group (0.37 ± 0.11 μg/g, P  < 0.001). Also, the concentrations of retained gadolinium in DCN were increased in the LF&GD group (0.13 ± 0.06 μg/g) compared to the LF group (0.01 ± 0.00 μg/g, P  < 0.001) and GD group (0.06 ± 0.02 μg/g, P  = 0.019). No histopathological alterations were detected in the liver and DCN between LF&GD group and LF group., Conclusions: LF aggravated gadolinium deposition in the liver and DCN after administration of GD. However, no significant acute histological alterations were observed due to gadolinium deposition., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: To detect and analyze risk signals of the drug-related adverse events (AEs) of 4 gadolinium-based contrast agents (GBCAs) (gadopentetate dimeglumine (Gd-DTPA), gadobenate dimeglumine (Gd-BOPTA), gadoteridol (Gd-HP-DO3A), and gadobutrol (Gd-BT-DO3A)) according to the US Food and Drug Administration Adverse Event Reporting System (FAERS) database and ensure the clinical safety., Research Design and Methods: The AEs that are associated with the 4 GBCAs were collected from the FAERS database from 2004Q1 to 2022Q3. The risk signals were mined using reporting odds ratio (ROR) and proportional reporting ratio (PRR)., Results: 424 risk signals were excavated, in which 151 risk signals were associated with Gd-DTPA, 93 risk signals were related to Gd-BOPTA, 79 risk signals were relevant to Gd-HP-DO3A, and 101 risk signals were associated with Gd-BT-DO3A. The AE signals involved 20 system organ classes (SOCs). Two of the top four SOCs were identical, namely 'skin and subcutaneous tissue disorders' and 'general disorders and administration site conditions.', Conclusions: The safety signals of 4 GBCAs were detected, and the SOCs associated with the AEs of the 4 GBCAs were different. Besides, some AEs obtained in this study were not mentioned in the package inserts, which need more attention and research to ensure the clinical safety.

Graphical abstract Highlights • T1-shortening of water protons in nerve cells by a macrocyclic contrast agent. • Injection of macrocyclic gadolinium-based agent into the lateral ventricle of mice. • In vivo MRI visibility of noradrenergic neuron groups and the nucleus ambiguus. • Saturation of extracellular and lipid-associated intracellular water protons. • Preservation of intracellular paramagnetic-ion-associated water proton signals. Abstract Three-dimensional T 1 -weighted MRI of mouse brain in vivo (9.4 T, 80 μm isotropic resolution) identified assemblies of nerve cell bodies in the habenula, hippocampal formation, locus coeruleus, dorsal motor nucleus of vagus, and nucleus ambiguus as high signal intensities, while suppressing the signals of white matter by magnetization transfer and of extracellular water protons by saturation. These observations indicate the presence of intracellular water protons with T 1 values shortened by paramagnetic ions as the source of the bright signal. One day after an intraventricular injection of gadobutrol, a macrocyclic gadolinium-based contrast agent, T 1 -weighted MRI signal intensities of the nerve cell assemblies in the habenula, hippocampal formation, and locus coeruleus increased significantly. With simultaneous saturation of long-T 1 protons of extracellular water, this finding indicates a T 1 -shortening of the intracellular water protons as a result of their interaction with gadolinium ions. [ABSTRACT FROM AUTHOR]

Background: Pediatric patients with inflammatory bowel disease (IBD) are at increased risk of gadolinium deposition given the potential need for multiple contrast-enhanced magnetic resonance enterography (MRE) exams over their lifetime.Objective: To determine whether gadolinium-based contrast agents are necessary in assessing active bowel inflammation on MRE in pediatric patients with known or suspected IBD.Materials and Methods: We conducted a retrospective study of 77 patients (7-18 years; 68.8% male) with known (n=58) or suspected (n=19) IBD and endoscopy with biopsy performed within 30 days of MRE without and with contrast evaluated bowel and non-bowel findings. During three visual analysis sessions, two radiologists reviewed pre-, post-, and pre-/post-contrast MRE images. A third radiologist independently reviewed 27 studies to assess inter-reader reliability. We used Cohen kappa (κ), Fleiss kappa, (κF), McNemar test, and sensitivity and specificity to compare MRE readings to combined endoscopic/histopathological findings (the reference standard).Results: The pre- and pre-/post-contrast-enhanced MRE vs. combined endoscopic/histopathological results had moderate agreement (85.7%; κ 0.713, P<0.001; P-value 0.549). Compared to combined endoscopy/histopathology, pre- vs. pre-/post-contrast sensitivity (67%, confidence interval [CI] 0.53-0.79 vs. 67%, CI 0.53-0.79) and specificity (80%, CI 0.59-0.92 vs. 68%, CI 0.46-0.84) varied little (κ 0.42, P<0.001 and κ 0.32, P=0.003, respectively). The three readers had moderate agreement (85.2%; κ 0.695, P=0.001; P-value 0.625). More penetrating complications were identified following contrast administration (P-value 0.04).Conclusion: Use of a contrast agent does not improve the detection of active inflammation in the terminal ileum and colon compared to non-contrast MRE, although use of a contrast agent does aid in the detection of penetrating disease. [ABSTRACT FROM AUTHOR]

• SI changes are unreliable parameters to evaluate gadolinium deposition in the brain. • SI changes are also unreliable to identify factors that affect gadolinium deposition. • No factor had a consistent influence on SI changes for either reader. To evaluate the reliability of signal intensity (SI) changes in the basal ganglia as a supposed indicator of gadolinium deposition in the brain after repetitive application of gadolinium-based contrast agents (GBCAs) in a pediatric neuro-oncological collective. One hundred and eight neuropediatric patients (54 male, 54 female, 0–17 years old), with repetitive GBCA-enhanced cranial MRIs between 2003 and 2017, were retrospectively analyzed. Two radiologists measured SI in the nucleus dentatus (ND), globus pallidus (GP), thalamus (T), and the pons (P). The N D P and G P T ratio were calculated. An intraclass correlation coefficient, and multiple linear regressions with subsequent stepwise backward variable selection were performed to evaluate the influence of gender, patient's age at the first MRI, time interval between the first and last MRI, linear or macrocyclic GBCAs, residual pathology, treatments, and magnet field strengths. The inter-reader agreement was good for G P T and N D P in the whole collective (ICC = 0.837 and ICC = 0.793) and for children >2 years of age (ICC = 0.874 and ICC = 0.790), but poor to moderate for children ≤2 years of age (ICC = 0.397 and ICC = 0.748). The intra-reader agreement was good (ICC = 0.910 and ICC = 0.882). An SI increase was only observed for both readers in G P T (p = 0.003, or p < 0.001). None of the considered cofactors showed a consistent effect on SI changes for either readers or regions. Measurements of SI changes in the basal ganglia are not a reliable parameter with which to evaluate or estimate gadolinium deposition in the brain or to identify suspicious influential factors after repeated GBCA applications. [ABSTRACT FROM AUTHOR]

Growing extraction and usage of rare earth elements and yttrium (REY) for medical and industrial applications has resulted in increased discharges into the marine environment. Using Mytilus spp. Mussels and Tapes spp. clams as bioindicator organisms, we analyzed 15 REY in soft tissues of specimens collected at two potentially polluted sites in Southern Norway: in the vicinity of an industry producing gadolinium-based MRI contrast agents (GBCAs) (Lindesnes) and in an industrially-affected fjord (Porsgrunn). The spatial distribution of REY and shale-normalized fractionation patterns were determined to assess the potential anthropogenic contribution of REY at the sites. At both sites, the REY fractionation pattern in soft tissue was characterized by enrichment of light rare earth elements (LREE) over heavy rare earth elements (HREE), while also displaying negative cerium and small positive gadolinium (Gd) anomalies. LREEs contributed to over 80% of the total REY concentrations, with increasing relative enrichment following higher total REY. Gd anomalies remained conserved in most sites despite significant differences in total REY; however, a high Gd anomaly (Gd/Gd* = 4.4) was found downstream of the GBCA industry spillwater outlet, indicating biotic uptake of excess anthropogenic Gd at this site. Total REY concentrations in clams in Porsgrunn were one order of magnitude higher than in mussels in Lindesnes. This may be attributable to freshwater influences in Porsgrunn, where clams collected closer to the river mouth had significantly higher total REY concentrations. This study constitutes the first assessment of REY concentrations in marine bivalves in Norway and can provide useful information for future biomonitoring studies on REY contamination. [Display omitted] • Rare earth elements were measured in marine bivalves at two potential release hot spots in Norway. • Mytilus spp. downstream a Gd-based contrast agent producing industry outfall accumulated Gd. • Tapes spp. had high levels of rare earth elements in a freshwater influenced industrial area. • Normalized patterns showed light rare earth element enrichment, negative Ce- and positive Gd anomalies. [ABSTRACT FROM AUTHOR]

Gadolinium-based contrast agents (GBCAs) are widely used in medical imaging, with greater than 300 million doses administered since their introduction. The risk of adverse reactions is very low, and GBCAs were thought to be very safe until the discovery of nephrogenic systemic fibrosis (NSF). Since that time, gadolinium has been found to deposit throughout the body, including the brain, where it is visible on non-contrast T1-weighted MR images in people with normal renal function. The clinical effects of this deposition remain unknown and may not exist. In this review the authors provide a comprehensive update on GBCAs and their potential risks, within a historical context and through the lens of a pediatric radiologist. [ABSTRACT FROM AUTHOR]

Abstract: Since the 1980s, gadolinium (Gd)–based contrast agents (GBCAs) have been routinely used in magnetic resonance imaging as stable chelates of the Gd3+ ion, without toxic effects. Generally, GBCAs are considered some of the safest contrast agents. However, it has been observed that they can accumulate in patient tissue, bone, and probably brain (causing nephrogenic systemic fibrosis in patients with kidney failure or insufficiency and disturbance of calcium homeostasis in the organism). The GBCAs are predominantly removed renally without metabolization. Subsequently, they do not undergo degradation processes in wastewater‐treatment plants and are emitted into the aquatic ecosystem. Their occurrence was confirmed in surface waters (up to 1100 ng/L), sediments (up to 90.5 μg/g), and living organisms. Based on a literature review, there is a need to investigate the contamination of different ecosystems and to ascertain the environmental fate of Gd. Long‐term ecotoxicological data, degradation, metabolism, bioaccumulation processes, and biochemical effects of the Gd complexes should be explored. These data can be used to assess detailed environmental risks because currently only hotspots with high levels of Gd can be marked as dangerous for aquatic environments according to environmental risk assessments. Environ Toxicol Chem 2018;37:1523–1534. © 2018 SETAC [ABSTRACT FROM AUTHOR]

At present, most of the cardiac magnetic resonance imaging (MRI) examinations rely on contrast-enhanced protocols, but noncontrast alternatives are emerging. Late gadolinium enhancement (LGE) imaging for the detection of myocardial scar can be considered the main cause for the embedding of cardiac MRI into the clinical routine. The novel noncontrast technique of native T1 mapping shows promise for tissue characterization in ischemic and nonischemic cardiomyopathy and may provide additional information over conventional LGE imaging. Technical issues, including measurements variability, still need to be resolved to facilitate a wide clinical application. Ischemia detection can be performed with contrast-based stress perfusion and contrast-free stress wall motion imaging. For coronary magnetic resonance angiography (MRA), protocols with and without contrast material have been developed. Research on coronary atherosclerotic plaque characterization has introduced new applications of contrast material. For MRA of the aorta, which traditionally relied on contrast administration, several noncontrast protocols have become available. This review provides an overview of when to use contrast material in cardiac and cardiac-related vascular MRI, summarizes the major imaging building blocks, and describes the diagnostic value of the available contrast-enhanced and noncontrast techniques. Contrast material in cardiac MRI should be used for LGE imaging for tissue characterization in ischemic or nonischemic cardiomyopathy and may be used for stress perfusion imaging for the detection of ischemia. In cardiac-related vascular MRI, use of contrast material should be avoided, unless high-quality angiography is required that cannot be obtained with noncontrast protocols.Level Of Evidence: 5 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1551-1572. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of pregnancy and type of gadolinium (Gd)-based contrast agents (GBCAs) on organ retention of Gd in mother and pup mice after maternal administration.Materials and Methods: Gd-DTPA-BMA (gadodiamide) or Gd-DOTA (gadoterate dimeglumine) was administered (2.0 mmol/kg of maternal weight) four times to pregnant Balb/c mice from gestational day 16-19, respectively. At 28 days after birth, they were euthanized and their organs (blood, brain, liver, kidney, spleen, and bone) were removed for the measurement of Gd by inductively coupled plasma mass spectrometry.Results: Gd retention in maternal organs was generally lower than that in the organs of non-pregnant mice in both Gd-DTPA-BMA and Gd-DOTA groups. Significantly higher Gd retention was observed in the organs of pups whose mothers were administered Gd-DTPA-BMA as compared to those whose mothers were administered Gd-DOTA. Tissue-to-muscle ratio in the brains of pups was higher than that of mothers.Conclusion: We demonstrated in utero transplacental Gd retention in pups. In various organs in both mothers and pups, Gd retention was consistently higher for Gd-DTPA-BMA than Gd-DOTA administration. Pregnancy affected Gd retention in many maternal organs. [ABSTRACT FROM AUTHOR]

Gadolinium-based contrast agents (GBCAs) have been used in magnetic resonance imaging (MRI) since the 1980s and are now administered in up to 35% of all MRI examinations. While GBCAs were initially felt to carry minimal risk, the subsequent identification of GBCAs as the key etiologic factor in the development of nephrogenic systemic fibrosis (NSF) has raised concerns about the broader health impacts of gadolinium exposure. Clinicians, radiologists, and patients should be aware of the most up-to-date data pertaining to the risks of GBCA administration. Specific issues covered in this review article include immediate adverse reactions; pregnancy and lactation; and gadolinium deposition and toxicity, with a special focus on NSF. Practice recommendations based on the presented data, as well as current professional society guidelines, are provided for each section.Level Of Evidence: 1 Technical Efficacy: Stage 5 J. MAGN. RESON. IMAGING 2017;46:338-353. [ABSTRACT FROM AUTHOR]

Background: Gadolinium-based contrast agents (GBCAs) have been used for magnetic resonance (MR) imaging over the last three decades. Recent reports demonstrated gadolinium retention in patients' brains following intravenous administration. Since gadolinium is a highly toxic heavy metal, there is a potential for adverse effects from prolonged retention or deposition, particularly in children. For this reason, the Society (SPR) for Pediatric Radiology Quality and Safety committee conducted a survey to evaluate the current status of GBCAs usage among pediatric radiologists. Objective: To assess the usage of GBCAs among SPR members. Materials and methods: An online 15-question survey was distributed to SPR members. Survey questions pertained to the type of GBCAs used, protocoling workflow, requirement of renal function or pregnancy tests, and various clinical indications for contrast-enhanced MRI examinations. Results: A total of 163 survey responses were compiled (11.1% of survey invitations), the majority of these from academic institutions in the United States. Ninety-four percent reported that MR studies are always or usually protocoled by pediatric radiologists. The most common GBCA utilized by survey respondents were Eovist (60.7%), Ablavar (45.4%), Gadovist (38.7%), Magnevist (34.4%) and Dotarem (32.5%). For several clinical indications, survey responses regarding GBCA administration were concordant with American College of Radiology (ACR) Appropriateness Criteria, including seizures, headache and osteomyelitis. For other indications, including growth hormone deficiency and suspected vascular ring, survey responses revealed potential overutilization of GBCAs when compared to ACR recommendations. Conclusion: Survey results demonstrate that GBCAs are administered judiciously in children, yet there is an opportunity to improve their utilization with the goal of reducing potential future adverse effects. [ABSTRACT FROM AUTHOR]

Gadolinium-based contrast agents can increase the accuracy and expediency of an MRI examination. However the benefits of a contrast-enhanced scan must be carefully weighed against the well-documented risks associated with administration of exogenous contrast media. The purpose of this review is to discuss commercially available gadolinium-based contrast agents (GBCAs) in the context of pediatric radiology. We discuss the chemistry, regulatory status, safety and clinical applications, with particular emphasis on imaging of the blood vessels, heart, hepatobiliary tree and central nervous system. We also discuss non-GBCA MRI contrast agents that are less frequently used or not commercially available. [ABSTRACT FROM AUTHOR]