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Recent studies have raised broad safety and health concerns about using of gadolinium contrast agents during magnetic resonance imaging (MRI) to enhance identification of active tumors. In this paper, we developed a deep learning‐based method for three‐dimensional (3D) contrast‐enhanced T1‐weighted (T1) image synthesis from contrast‐free image(s). The MR images of 1251 patients with glioma from the RSNA‐ASNR‐MICCAI BraTS Challenge 2021 dataset were used in this study. A 3D dense‐dilated residual U‐Net (DD‐Res U‐Net) was developed for contrast‐enhanced T1 image synthesis from contrast‐free image(s). The model was trained on a randomly split training set (n = 800) using a customized loss function and validated on a validation set (n = 200) to improve its generalizability. The generated images were quantitatively assessed against the ground‐truth on a test set (n = 251) using the mean absolute error (MAE), mean‐squared error (MSE), peak signal‐to‐noise ratio (PSNR), structural similarity (SSIM), normalized mutual information (NMI), and Hausdorff distance (HDD) metrics. We also performed a qualitative visual similarity assessment between the synthetic and ground‐truth images. The effectiveness of the proposed model was compared with a 3D U‐Net baseline model and existing deep learning‐based methods in the literature. Our proposed DD‐Res U‐Net model achieved promising performance for contrast‐enhanced T1 synthesis in both quantitative metrics and perceptual evaluation on the test set (n = 251). Analysis of results on the whole brain region showed a PSNR (in dB) of 29.882 ± 5.924, a SSIM of 0.901 ± 0.071, a MAE of 0.018 ± 0.013, a MSE of 0.002 ± 0.002, a HDD of 2.329 ± 9.623, and a NMI of 1.352 ± 0.091 when using only T1 as input; and a PSNR (in dB) of 30.284 ± 4.934, a SSIM of 0.915 ± 0.063, a MAE of 0.017 ± 0.013, a MSE of 0.001 ± 0.002, a HDD of 1.323 ± 3.551, and a NMI of 1.364 ± 0.089 when combining T1 with other MRI sequences. Compared to the U‐Net baseline model, our model revealed superior performance. Our model demonstrated excellent capability in generating synthetic contrast‐enhanced T1 images from contrast‐free MR image(s) of the whole brain region when using multiple contrast‐free images as input. Without incorporating tumor mask information during network training, its performance was inferior in the tumor regions compared to the whole brain which requires further improvements to replace the gadolinium administration in neuro‐oncology.

Background and purpose The discovery of glymphatic function in the human brain has generated interest in waste clearance mechanisms in neurological disorders such as multiple sclerosis (MS). However, noninvasive in vivo functional assessment is currently lacking. This work studies the feasibility of a novel intravenous dynamic contrast MRI method to assess the dural lymphatics, a purported pathway contributing to glymphatic clearance. Methods This prospective study included 20 patients with MS (17 women; age = 46.4 [27, 65] years; disease duration = 13.6 [2.1, 38.0] years, expanded disability status score (EDSS) = 2.0 [0, 6.5]). Patients were scanned on a 3.0T MRI system using intravenous contrast‐enhanced fluid‐attenuated inversion recovery MRI. Signal in the dural lymphatic vessel along the superior sagittal sinus was measured to calculate peak enhancement, time to maximum enhancement, wash‐in and washout slopes, and the area under the time‐intensity curve (AUC). Correlation analysis was performed to examine the relationship between the lymphatic dynamic parameters and the demographic and clinical characteristics, including the lesion load and the brain parenchymal fraction (BPF). Results Contrast enhancement was detected in the dural lymphatics in most patients 2–3 min after contrast administration. BPF had a significant correlation with AUC (p < .03), peak enhancement (p < .01), and wash‐in slope (p = .01). Lymphatic dynamic parameters did not correlate with age, BMI, disease duration, EDSS, or lesion load. Moderate trends were observed for correlation between patient age and AUC (p = .062), BMI and peak enhancement (p = .059), and BMI and AUC (p = .093). Conclusion Intravenous dynamic contrast MRI of the dural lymphatics is feasible and may be useful in characterizing its hydrodynamics in neurological diseases. We study the feasibility of a novel intravenous, dynamic, contrast‐enhanced MRI method to assess the dural lymphatic vessels. Initial results in multiple sclerosis patients confirm feasibility, and show interesting associations between the lymphatic signal and patient characteristics. The proposed functional method could enable in vivo study of waste clearance mechanisms in neurological disorders.

Gadolinium-based contrast agents (GBCAs) have been used for more than 30 years to improve magnetic resonance imaging, a crucial tool for medical diagnosis and treatment monitoring across multiple clinical settings. Studies have shown that exposure to GBCAs is associated with gadolinium release and tissue deposition that may cause short- and long-term toxicity in several organs, including the kidney, the main excretion organ of most GBCAs. Considering the increasing prevalence of chronic kidney disease worldwide and that most of the complications following GBCA exposure are associated with renal dysfunction, the mechanisms underlying GBCA toxicity, especially renal toxicity, are particularly important. A better understanding of the gadolinium mechanisms of toxicity may contribute to clarify the safety and/or potential risks associated with the use of GBCAs. In this work, a review of the recent literature concerning gadolinium and GBCA mechanisms of toxicity was performed.

In the past 4 years, many publications described a concentration-dependent deposition of gadolinium in the brain both in adults and children, seen as high signal intensities in the globus pallidus and dentate nucleus on unenhanced T1-weighted images. Postmortem human or animal studies have validated gadolinium deposition in these T1-hyperintensity areas, raising new concerns on the safety of gadolinium-based contrast agents (GBCAs). Residual gadolinium is deposited not only in brain, but also in extracranial tissues such as liver, skin, and bone. This review summarizes the current evidence on gadolinium deposition in the human and animal bodies, evaluates the effects of different types of GBCAs on the gadolinium deposition, introduces the possible entrance or clearance mechanism of the gadolinium and potential side effects that may be related to the gadolinium deposition on human or animals, and puts forward some suggestions for further research.

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.

Gadolinium-based contrast agents (GBCA) are essential for diagnostic MRI examinations. GBCA are only used in small quantities on a per-patient basis; however, the acquisition of contrast-enhanced MRI examinations worldwide results in the use of many thousands of litres of GBCA per year. Data shows that these GBCA are present in sewage water, surface water, and drinking water in many regions of the world. Therefore, there is growing concern regarding the environmental impact of GBCA because of their ubiquitous presence in the aquatic environment. To address the problem of GBCA in the water system as a whole, collaboration is necessary between all stakeholders, including the producers of GBCA, medical professionals and importantly, the consumers of drinking water, i.e. the patients. This paper aims to make healthcare professionals aware of the opportunity to take the lead in making informed decisions about the use of GBCA and provides an overview of the different options for action.In this paper, we first provide a summary on the metabolism and clinical use of GBCA, then the environmental fate and observations of GBCA, followed by measures to reduce the use of GBCA. The environmental impact of GBCA can be reduced by (1) measures focusing on the application of GBCA by means of weight-based contrast volume reduction, GBCA with higher relaxivity per mmol of Gd, contrast-enhancing sequences, and post-processing; and (2) measures that reduce the waste of GBCA, including the use of bulk packaging and collecting residues of GBCA at the point of application.Critical relevance statement This review aims to make healthcare professionals aware of the environmental impact of GBCA and the opportunity for them to take the lead in making informed decisions about GBCA use and the different options to reduce its environmental burden.Key points• Gadolinium-based contrast agents are found in sources of drinking water and constitute an environmental risk.• Radiologists have a wide spectrum of options to reduce GBCA use without compromising diagnostic quality.• Radiology can become more sustainable by adopting such measures in clinical practice.

BackgroundRetained gadolinium from gadolinium-based contrast agents (GBCAs) used in MR exams has been inferred based on signal changes on serial brain MRI and subsequently demonstrated pathologically in adults. Retention has been similarly inferred in children but pathological demonstration in pediatric patients is limited. The long-term effects of retained gadolinium are unknown but are potentially of greater concern in children given their increased vulnerability from continuing development and their expected longer period of exposure. Several factors can influence gadolinium retention. In adults as well as in children, greater accumulation has been demonstrated based on MR signal changes with linear compared with macrocyclic gadolinium chelates, attributed to lower chelate affinity with linear agents. Effects of age at exposure on retention are unknown, while differences in GBCA washout rates are still under investigation and might affect gadolinium retention relative to time of GBCA administration.ObjectiveThe purpose of this study was to confirm whether gadolinium brain deposits are present in pediatric patients who received GBCAs and to quantify the amounts present.Materials and methodsBrain autopsy specimens from 10 pediatric patients between 1 year and 13 years of age who underwent at least one contrast-enhanced MR exam were analyzed for elemental gadolinium using inductively coupled plasma mass spectrometry. Brain samples included white matter, basal ganglia (putamen, globus pallidus), thalamus, dentate nucleus and tumor tissue as available. Type and dose of contrast agent, number and timing of contrast-enhanced MR exams and renal function (estimated glomerular filtration rate [eGFR]) were documented for each child.ResultsPatient exposures ranged from 1 dose to 20 doses of GBCAs including both macrocyclic and linear ionic agents. Gadolinium was found to be present in brain tissue in all children and was generally highest in the globus pallidus. Those who received only macrocyclic agents showed lower levels of gadolinium retention.ConclusionThis study demonstrates pathological confirmation of gadolinium retention in brain tissue of a series of pediatric patients exposed to GBCAs including not only linear ionic agents but also macrocyclic agents with both nonionic and ionic compounds. The distribution and deposition levels in this small pediatric population are comparable with the findings in adults. While the clinical significance of these deposits remains unknown, at this point it would be prudent to exert caution and avoid unnecessary use of GBCAs in pediatric patients.

Objectives The environmental footprint of iodinated contrast agents (ICAs) and gadolinium-based contrast agents (GBCAs) is noteworthy. This study assesses: (1) patients’ “green sensitivity” as measured by their acceptance in a sustainability study and (2) the resulting potential reduction of contrast residuals in wastewater. Materials and methods After ethical approval, participants scheduled for administration of ICAs or GBCAs for diagnostic purposes were enrolled in this prospective observational study from July 2022 to October 2023. They were asked to prolong their hospital stay by up to 60 min to collect their first urine in dedicated canisters, thereby measuring the recovery rates of ICAs and GBCAs as found/theoretical ratio of concentrations. Mann–Whitney U , χ 2 tests, and multivariable regression analysis were used. Results Patients scheduled for contrast-enhanced CT or MRI ( n  = 455) were screened; 422 (92.7%) accepted to participate. We enrolled 212 patients administered with ICAs and 210 administered with GBCAs. The median recovery rate was 51.2% (interquartile range 29.2–77.9%) for ICAs and 12.9% (9.0–19.3%) for GBCAs. At multivariable analysis, a significant effect of patient age (ICAs, p  = 0.001; GBCAs, p  = 0.014), urine volume ( p  < 0.001 for both), and time interval from contrast administration to urine collection ( p  < 0.001 for both) on recovery rates was found for both contrast agents; injected contrast volume ( p  = 0.046) and saline flushing usage ( p  = 0.008) showed a significant effect only for ICAs. Conclusion The high patient enrollment compliance (93%) and potential recovery rates of 51% (ICAs) and 13% (GBCAs) play in favor of sustainable practices in reducing the environmental footprint of contrast agents. Key Points Question How many patients are willing to extend their stay in radiology by up to 60   min to help reduce the environmental impact of contrast agents? Findings Over 90% of screened patients agreed to extend their stay by up to 60   min and collect their urine in dedicated containers. Clinical relevance Patients demonstrated a high willingness to cooperate in reducing the environmental impact of contrast agents, allowing for a potential recovery of approximately 51% for iodinated and 13% for gadolinium-based contrast agents. Graphical Abstract

Purpose A possible pathway behind gadolinium retention in brain is leakage of contrast agents from blood to cerebrospinal fluid and entry into brain along perivascular (glymphatic) pathways. The object of this study was to assess for signs of gadolinium retention in brain 4 weeks after intrathecal contrast enhanced MRI. Methods We prospectively applied standardized T1 mapping of the brain before and 4 weeks after intrathecal administration of 0.5 mmol gadobutrol in patients under work-up of cerebrospinal fluid circulation disorders. Due to methodological limitations, a safety margin for percentage change in T1 time was set to 3%. Region-wise differences were assessed by pairwise comparison using t -tests and forest plots, and statistical significance was accepted at .05 level (two-tailed). Results In a cohort of 76 participants (mean age 47.2 years ± 17.9 [standard deviation], 47 women), T1 relaxation times remained unchanged in cerebral cortex and basal ganglia 4 weeks after intrathecal gadobutrol. T1 was reduced from 1082 ± 46.7 ms to 1070.6 ± 36.5 ms (0.98 ± 2.9%) (mean [standard deviation]) ( p =0.001) in white matter, thus within the pre-defined 3% safety margin. The brain stem and cerebellum could not be assessed due to poor alignment of posterior fossa structures at scans from different time points. Conclusion Gadolinium retention was not detected in the cerebral hemispheres 4 weeks after an intrathecal dose of 0.5 mmol gadobutrol, implying that presence of contrast agents in cerebrospinal fluid is of minor importance for gadolinium retention in brain.

The extracellular class of gadolinium-based contrast agents (GBCAs) is an essential tool for clinical diagnosis and disease management. In order to better understand the issues associated with GBCA administration and gadolinium retention and deposition in the human brain, the chemical properties of GBCAs such as relative thermodynamic and kinetic stabilities and their likelihood of forming gadolinium deposits in vivo will be reviewed. The chemical form of gadolinium causing the hyperintensity is an open question. On the basis of estimates of total gadolinium concentration present, it is highly unlikely that the intact chelate is causing the T1 hyperintensities observed in the human brain. Although it is possible that there is a water-soluble form of gadolinium that has high relaxitvity present, our experience indicates that the insoluble gadolinium-based agents/salts could have high relaxivities on the surface of the solid due to higher water access. This review assesses the safety of GBCAs from a chemical point of view based on their thermodynamic and kinetic properties, discusses how these properties influence in vivo behavior, and highlights some clinical implications regarding the development of future imaging agents.