Use Of Gadolinium-based Contrast Agents Research Articles

Safe and Informed Use of Gadolinium-Based Contrast Agent in Body Magnetic Resonance Imaging: Where We Were and Where We Are.

Gadolinium-based contrast agents (GBCAs) have helped to improve the role of magnetic resonance imaging (MRI) for the diagnosis and treatment of diseases. There are currently nine different commercially available gadolinium-based contrast agents (GBCAs) that can be used for body MRI cases, and which are classifiable according to their structures (cyclic or linear) or biodistribution (extracellular-space agents, target/specific-agents, and blood-pool agents). The aim of this review is to illustrate the commercially available MRI contrast agents, their effect on imaging, and adverse reaction on the body, with the goal to lead to their proper selection in different clinical contexts. When we have to choose between the different GBCAs, we have to consider several factors: (1) safety and clinical impact; (2) biodistribution and diagnostic application; (3) higher relaxivity and better lesion detection; (4) higher stability and lower tissue deposit; (5) gadolinium dose/concentration and lower volume injection; (6) pulse sequences and protocol optimization; (7) higher contrast-to-noise ratio at 3.0 T than at 1.5 T. Knowing the patient's clinical information, the relevant GBCAs properties and their effect on body MRI sequences are the key features to perform efficient and high-quality MRI examination.

Toxicity Mechanisms of Gadolinium and Gadolinium-Based Contrast Agents-A Review.

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.

Assessment of the accuracy of biparametric MRI/TRUS fusion-guided biopsy for index tumor evaluation using postoperative pathology specimens

BackgroundMultiparametric MRI (mpMRI) is widely used for the diagnosis, surveillance, and staging of prostate cancer. However, it has several limitations, including higher costs, longer examination times, and the use of gadolinium-based contrast agents. This study aimed to investigate the accuracy of preoperatively assessed index tumors (ITs) using biparametric MRI (bpMRI)/transrectal ultrasound (TRUS) fusion biopsy compared with radical prostatectomy (RP) specimens.MethodsWe included 113 patients diagnosed with prostate cancer through bpMRI/TRUS fusion-guided biopsies of lesions with a Prostate Imaging Reporting and Data System (PI-RADS) category ≥ 3. These patients underwent robot-assisted laparoscopic radical prostatectomy (RARP) at our institution between July 2017 and March 2023. We examined the localization of preoperative and postoperative ITs, the highest Gleason score (GS), and tumor diameter in these patients.ResultsThe preoperative cT stage matched the postoperative pT stage in 53 cases (47%), while 31 cases (27%) were upstaged, and 29 cases (26%) were downstaged (Weighted Kappa = 0.21). The preoperative and postoperative IT localizations were consistent in 97 cases (86%). The concordance rate between Gleason groups in targeted biopsies and RP specimens was 51%, with an upgrade in 25 cases (23%) and a downgrade in 27 cases (25%) (Weighted Kappa = 0.42). The maximum diameter of the IT and the maximum cancer core length on biopsy were correlated with the RP tumor's maximum diameter (p < 0.001 for both).ConclusionThe diagnostic accuracy of bpMRI/TRUS fusion biopsy is comparable to mpMRI, suggesting that it can be a cost-effective and time-saving alternative.

Contrast Media-driven Anthropogenic Gadolinium: Knowns and Unknowns.

Gadolinium-based contrast agents (GBCAs) have augmented the capabilities of MRI, which has led to their widespread and increasing use in radiology practice. GBCAs are introduced into the environment through disposal of unused product and elimination after intravenous injection, both primarily via liquid dispersion into the environment. This human introduction of gadolinium into the environment, referred to as anthropogenic gadolinium, is associated with the detection of gadolinium in water systems, raising concerns for potential adverse impact and prompting certain mitigation actions. This article summarizes the existing knowledge and problem scope, conveys the relevant underlying chemical principles of chelate dissociation, and offers an inferred perspective that the magnitude of the problem is most unlikely to cause human harm. The merits and limitations regarding possible mitigation tactics, such as collecting urine after GBCA administration, use of lower-dose high-relaxivity macrocyclic GBCAs, and the option for virtual contrast-enhanced examinations, will be discussed. Finally, the potential for monitoring gadolinium uptake in bone will be presented, and recommendations for future research will be offered. © RSNA, 2024 See also the article by Ibrahim et al in this issue. See also the article by McKee et al in this issue.

Brain Tumor Imaging without Gadolinium-based Contrast Agents: Feasible or Fantasy?

Gadolinium-based contrast agents (GBCAs) form the cornerstone of current primary brain tumor MRI protocols at all stages of the patient journey. Though an imperfect measure of tumor grade, GBCAs are repeatedly used for diagnosis and monitoring. In practice, however, radiologists will encounter situations where GBCA injection is not needed or of doubtful benefit. Reducing GBCA administration could improve the patient burden of (repeated) imaging (especially in vulnerable patient groups, such as children), minimize risks of putative side effects, and benefit costs, logistics, and the environmental footprint. On the basis of the current literature, imaging strategies to reduce GBCA exposure for pediatric and adult patients with primary brain tumors will be reviewed. Early postoperative MRI and fixed-interval imaging of gliomas are examples of GBCA exposure with uncertain survival benefits. Half-dose GBCAs for gliomas and T2-weighted imaging alone for meningiomas are among options to reduce GBCA use. While most imaging guidelines recommend using GBCAs at all stages of diagnosis and treatment, non-contrast-enhanced sequences, such as the arterial spin labeling, have shown a great potential. Artificial intelligence methods to generate synthetic postcontrast images from decreased-dose or non-GBCA scans have shown promise to replace GBCA-dependent approaches. This review is focused on pediatric and adult gliomas and meningiomas. Special attention is paid to the quality and real-life applicability of the reviewed literature.

Model Generalizability Investigation for GFCE-MRI Synthesis in NPC Radiotherapy Using Multi-Institutional Patient-Based Data Normalization.

Recently, deep learning has been demonstrated to be feasible in eliminating the use of gadoliniumbased contrast agents (GBCAs) through synthesizing gadolinium-free contrast-enhanced MRI (GFCE-MRI) from contrast-free MRI sequences, providing the community with an alternative to get rid of GBCAs-associated safety issues in patients. Nevertheless, generalizability assessment of the GFCE-MRI model has been largely challenged by the high inter-institutional heterogeneity of MRI data, on top of the scarcity of multi-institutional data itself. Although various data normalization methods have been adopted to address the heterogeneity issue, it has been limited to single-institutional investigation and there is no standard normalization approach presently. In this study, we aimed at investigating generalizability of GFCE-MRI model using data from seven institutions by manipulating heterogeneity of MRI data under five popular normalization approaches. Three state-of-the-art neural networks were applied to map from T1-weighted and T2-weighted MRI to contrast-enhanced MRI (CE-MRI) for GFCE-MRI synthesis in patients with nasopharyngeal carcinoma. MRI data from three institutions were used separately to generate three uni-institution models and jointly for a tri-institution model. The five normalization methods were applied to normalize the data of each model. MRI data from the remaining four institutions served as external cohorts for model generalizability assessment. Quality of GFCE-MRI was quantitatively evaluated against ground-truth CE-MRI using mean absolute error (MAE) and peak signal-to-noise ratio(PSNR). Results showed that performance of all uni-institution models remarkably dropped on the external cohorts. By contrast, model trained using multi-institutional data with Z-Score normalization yielded the best model generalizability improvement.

Investigating the feasibility of differentiating MS active lesions from inactive ones using texture analysis and machine learning methods in DWI images

BackgroundMagnetic resonance imaging (MRI) is commonly used in conjunction with a gadolinium-based contrast agent (GBCA) to distinguish active multiple sclerosis (MS) lesions. However, recent studies have raised concerns regarding the long-term effects of the accumulation of GBCA in the body. Thus, the purpose of this study is to investigate the possibility of using texture analysis in diffusion-weighted imaging (DWI) and machine learning algorithms to discriminate active from inactive MS lesions without the use of GBCA. MethodsTo achieve this purpose, we introduce an image processing pipeline. In the proposed pipeline, following registration and alignment of slices, MS lesions from DWI images are segmented and quantized. Next, different texture analysis methods are employed to extract texture features from the lesions. Then, a two-stage feature reduction method is applied, in which the first stage involves a statistical t-test and the second stage relies on principal component analysis (PCA), sequential forward selection (SFS), sequential backward selection (SBS), and ReliefF algorithms. Finally, we use five classifiers logistic regression (LR), support vector machine (SVM), decision tree (DT), K nearest neighbor (KNN), and linear discriminant analysis (LDA) in a 5-fold cross-validation procedure to determine active and inactive MS lesions. ResultsIn this study, we collected and prepared 255 active/inactive MS lesions from MRI scans of 34 patients diagnosed with MS, with a mean age of 35.56±10.89. Among 89 texture features extracted, 63 features showed statistically significant differences between the means of active and inactive lesions (P<0.05). The SVM classifier with the PCA feature reduction algorithm demonstrated the best performance with an average accuracy of 0.960 (±0.024), specificity and precision of 1.0, sensitivity of 0.913 (±0.053), and AUC of 0.957 (±0.027). ConclusionOur study indicates that DWI changes detected using texture analysis-based machine learning models can precisely differentiate active from inactive MS lesions. This finding provides valuable clinical information for the early diagnosis and effective monitoring of MS disease.

Use of gadolinium-based contrast agents in multiple sclerosis: a review by the ESMRMB-GREC and ESNR Multiple Sclerosis Working Group.

Magnetic resonance imaging (MRI) is the most sensitive technique for detecting inflammatory demyelinating lesions in multiple sclerosis (MS) and plays a crucial role in diagnosis and monitoring treatment effectiveness, and for predicting the disease course. In clinical practice, detection of MS lesions is mainly based on T2-weighted and contrast-enhanced T1-weighted sequences. Contrast-enhancing lesions (CEL) on T1-weighted sequences are related to (sub)acute inflammation, while new or enlarging T2 lesions reflect the permanent footprint from a previous acute inflammatory demyelinating event. These two types of MRI features provide redundant information, at least in regular monitoring of the disease. Due to the concern of gadolinium deposition after repetitive injections of gadolinium-based contrast agents (GBCAs), scientific organizations and regulatory agencies in Europe and North America have proposed that these contrast agents should be administered only if clinically necessary. In this article, we provide data on the mode of action of GBCAs in MS, the indications of the use of these agents in clinical practice, their value in MS for diagnostic, prognostic, and monitoring purposes, and their use in specific populations (children, pregnant women, and breast-feeders). We discuss imaging strategies that achieve the highest sensitivity for detecting CELs in compliance with the safety regulations established by different regulatory agencies. Finally, we will briefly discuss some alternatives to the use of GBCA for detecting blood-brain barrier disruption in MS lesions. CLINICAL RELEVANCE STATEMENT: Although use of GBCA at diagnostic workup of suspected MS is highly valuable for diagnostic and prognostic purposes, their use in routine monitoring is not mandatory and must be reduced, as detection of disease activity can be based on the identification of new or enlarging lesions on T2-weighted images. KEY POINTS: • Both the EMA and the FDA state that the use of GBCA in medicine should be restricted to clinical scenarios in which the additional information offered by the contrast agent is required. • The use of GBCA is generally recommended in the diagnostic workup in subjects with suspected MS and is generally not necessary for routine monitoring in clinical practice. • Alternative MRI-based approaches for detecting acute focal inflammatory MS lesions are not yet ready to be used in clinical practice.

Is non-contrast MRI sufficient to detect meningioma residue after surgery?

BackgroundContrast-enhanced magnetic resonance imaging (MRI) is the imaging modality routinely used to follow up patients who have undergone surgical resection of brain meningiomas. There are growing concerns about the massive use of gadolinium-based contrast agents (GBCA). Our aim was to evaluate the performance of a new imaging protocol, performed without GBCA injection, in the detection of tumoral residue or local recurrence after surgery of parafalcine and convexity meningiomas. Materials and methodsOnly adult patients with a documented resected parafalcine or convexity meningioma were included. We performed a dedicated MRI protocol that included non-contrast and post-contrast sequences. The presence or absence of residue on the unenhanced sequences was independently recorded by three observers: first blindly, then in comparison with a baseline enhanced MRI examination. ResultsA total of 51 patients were included. 37 of them featured a tumor residue on the reference enhanced sequence. Overall, an average of 32 of 37 (87%) residues were identified on the unenhanced sequences that were blindly reviewed; and more than 34 of 37 (93%) were identified with the help of the comparative baseline enhanced examination, with a high sensitivity. The missed cases were related to small residues. ConclusionUnenhanced MRI sequences are highly sensitive and specific in identifying a tumor residue or a local recurrence in the post operative follow up of brain meningiomas. Sensitivity is even higher with the help of a comparative baseline enhanced MRI examination, whatever the strength of magnetic field.

Comparison of Methemoglobin, Deoxyhemoglobin, and Ferrous Nitrosyl Hemoglobin as Potential MRI Contrast Agents.

Gadolinium-based contrast agents (GBCAs) are in widespread use to enhance magnetic resonance imaging for evaluating vascular pathology. However, safety concerns and limitations regarding the use of GBCAs has led to an increased interest in alternative contrast agents. Previously, methemoglobin (metHb) and oxygen-free hemoglobin (HHb) have been shown to increase the T1-weighted signal intensity of blood, which is associated with a decrease in the T1 parameter and an enhanced contrast of the image. Thus, a lower T1 value compared to the baseline value is favorable for imaging. However, it is unknown as to whether metHb or HHb would be a stronger and more appropriate contrast agent and to what extent the T1-weighted signal is affected by concentration. This study evaluated T1-weighted images of blood samples over a range of metHb and HHb concentrations, as well as ferrous nitrosyl hemoglobin (HbIINO) concentrations. Comparison of T1 values from a baseline value of ~ 1500ms showed that metHb is the strongest contrast agent (T1 ~ 950ms at 20% metHb) and that HHb is a relatively weak contrast agent (T1 ~ 1450ms at 20% HHb). This study showed for the first time that HbIINO can provide a contrast effect, although not as strong as metHb but stronger than HHb (T1 estimated as 1250ms at 20% HbIINO). With metHb providing a viable contrast between 10 and 20%, metHb has the potential to be a safe and effective contrast agent since it can be naturally converted back to hemoglobin.

Multiple sclerosis imaging in clinical practice: a European-wide survey of 428 centers and conclusions by the ESNR Working Group.

To evaluate compliance with the available recommendations, we assessed the current clinical practice of imaging in the evaluation of multiple sclerosis (MS). An online questionnaire was emailed to all members and affiliates. Information was gathered on applied MR imaging protocols, gadolinium-based contrast agents (GBCA) use and image analysis. We compared the survey results with the Magnetic Resonance Imaging in MS (MAGNIMS) recommendations considered as the reference standard. A total of 428 entries were received from 44 countries. Of these, 82% of responders were neuroradiologists. 55% performed more than ten scans per week for MS imaging. The systematic use of 3T is rare (18%). Over 90% follow specific protocol recommendations with 3D FLAIR, T2-weighted and DWI being the most frequently used sequences. Over 50% use SWI at initial diagnosis and 3D gradient-echo T1-weighted imaging is the most used MRI sequence for pre- and post-contrast imaging. Mismatches with recommendations were identified including the use of only one sagittal T2-weighted sequence for spinal cord imaging, the systematic use of GBCA at follow-up (over 30% of institutions), a delay time shorter than 5min after GBCA administration (25%) and an inadequate follow-up duration in pediatric acute disseminated encephalomyelitis (80%). There is scarce use of automated software to compare images or to assess atrophy (13% and 7%). The proportions do not differ significantly between academic and non-academic institutions. While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that recommendations are only partially followed. Hurdles were identified, mainly in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies. This work will help radiologists to identify the mismatches between their own practices and the recommendations and act upon them. • While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that available recommendations are only partially followed. • Several hurdles have been identified through the survey that mainly lies in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies.

Approach to Balancing Risk in Multiple Sclerosis Management: a Worldwide Practice Survey (P14-3.013)

<h3>Objective:</h3> To explore practice differences in prevailing treatment strategies of multiple sclerosis. <h3>Background:</h3> Available disease-modifying therapies (DMTs) for MS are rapidly expanding; this coincides with debate surrounding DMT selection and treatment strategies. Although escalation approaches have been previously favored to balance safety and efficacy, emerging evidence suggests superior outcomes for MS patients who are exposed to high-efficacy therapies early on. Additionally, there is growing controversy regarding use of gadolinium-based contrast agents in routine monitoring due to risk of gadolinium deposition. <h3>Design/Methods:</h3> We used a worldwide electronic survey launched by the Practice Current section of Neurology® Clinical Practice. Practice-related questions pertained to a case of a 37-year-old female presenting with unilateral optic neuritis alongside non-enhancing lesions in the cerebellum and spinal cord. Respondents were asked to indicate their initial investigations, relapse-management strategy, choice of disease modifying therapy, and plan for follow-up imaging (contrast/non-contrast). Multivariable analysis was precluded by low response numbers. <h3>Results:</h3> We received 153 responses from 42 countries; 32.3% identified as MS specialists. There was a strong preference for intravenous (rather than oral) delivery of high-dose corticosteroids (87.7% vs. 8.0%) and 61.3% indicated they would treat a non-disabling (mild sensory) MS relapse. Given the described clinical scenario, 59.4% felt the patient was at risk of a severe MS course. When asked to select a single initial DMT, 55.8% selected a high-efficacy therapy (67.5% MS specialists vs. 52.4% non-MS specialists). The most selected agents overall were fingolimod (14.7%), natalizumab (15.5%) and dimethyl fumarate (20.9%). Two-thirds of respondents (69.2%) indicated they would request contrast enhanced (vs. non-enhanced) MRI for follow-up imaging (61.9% MS specialists vs. 70.1% non-MS specialists). <h3>Conclusions:</h3> Although there is a slight preference for initiating high-efficacy DMT at the time of initial MS diagnosis, opinions regarding the most appropriate treatment paradigm remain divided. <b>Disclosure:</b> An immediate family member of Dr. Roberts has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amylyx Pharmaceuticals. The institution of Dr. Roberts has received research support from Canadian Network of MS Clinics. Dr. Roberts has received research support from Rebecca Hotchkiss International Exchange Program. Aravind Ganesh has nothing to disclose. Dr. Bartolini has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Academy of Neurology. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi Genzyme. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Merck. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving as a Consultant for National Health and Medical Research Council. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MS Research Australia. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bristol Myers Squibb. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for WebMD Global. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Novartis. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi Genzyme. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Teva. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for BioCSL. Tomas Kalincik has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Merck. Tomas Kalincik has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. The institution of Tomas Kalincik has received research support from Biogen. The institution of Tomas Kalincik has received research support from Novartis. The institution of Tomas Kalincik has received research support from Genzyme. The institution of Tomas Kalincik has received research support from Roche. The institution of Tomas Kalincik has received research support from Celgene. The institution of Tomas Kalincik has received research support from Merck. The institution of Tomas Kalincik has received research support from MSBase Foundation. The institution of Tomas Kalincik has received research support from ARSEP and EDMUS Foundations. The institution of Tomas Kalincik has received research support from MS Research Australia. The institution of Tomas Kalincik has received research support from National Health and Medical Research Council. The institution of Tomas Kalincik has received research support from Australian Research Council. The institution of Tomas Kalincik has received research support from MS Society. The institution of Tomas Kalincik has received research support from Trish Foundation. Tomas Kalincik has a non-compensated relationship as a scientific leadership group chair with MSBase Foundation that is relevant to AAN interests or activities.

The patients’ experience of neuroimaging of primary brain tumors: a cross-sectional survey study

PurposeTo gain insight into how patients with primary brain tumors experience MRI, follow-up protocols, and gadolinium-based contrast agent (GBCA) use.MethodsPrimary brain tumor patients answered a survey after their MRI exam. Questions were analyzed to determine trends in patients’ experience regarding the scan itself, follow-up frequency, and the use of GBCAs. Subgroup analysis was performed on sex, lesion grade, age, and the number of scans. Subgroup comparison was made using the Pearson chi-square test and the Mann–Whitney U-test for categorical and ordinal questions, respectively.ResultsOf the 100 patients, 93 had a histopathologically confirmed diagnosis, and seven were considered to have a slow-growing low-grade tumor after multidisciplinary assessment and follow-up. 61/100 patients were male, with a mean age ± standard deviation of 44 ± 14 years and 46 ± 13 years for the females. Fifty-nine patients had low-grade tumors. Patients consistently underestimated the number of their previous scans. 92% of primary brain tumor patients did not experience the MRI as bothering and 78% would not change the number of follow-up MRIs. 63% of the patients would prefer GBCA-free MRI scans if diagnostically equally accurate. Women found the MRI and receiving intravenous cannulas significantly more uncomfortable than men (p = 0.003). Age, diagnosis, and the number of previous scans had no relevant impact on the patient experience.ConclusionPatients with primary brain tumors experienced current neuro-oncological MRI practice as positive. Especially women would, however, prefer GBCA-free imaging if diagnostically equally accurate. Patient knowledge of GBCAs was limited, indicating improvable patient information.

European fluxes of medical gadolinium to the ocean: A model based on healthcare databases

Marine ecosystems are exposed to a multitude of stresses, including emerging metals as Rare Earth Elements. The management of these emerging contaminants represents a significant environmental issue. For the past three decades, the increasing medical use of gadolinium-based contrast agents (GBCAs) has contributed to their widespread dispersion in hydrosystems, raising concerns for ocean conservation. In order to control GBCA contamination pathways, a better understanding of the cycle of these elements is needed, based on the reliable characterization of fluxes from watersheds.Our study proposes an unprecedented annual flux model for anthropogenic gadolinium (Gdanth) based on GBCA consumption, demographics and medical uses. This model enabled the mapping of Gdanth fluxes for 48 European countries. The results show that 43 % of Gdanth is exported to the Atlantic Ocean, 24 % to the Black Sea, 23 % to the Mediterranean Sea and 9 % to the Baltic Sea. Together, Germany, France and Italy contribute 40 % of Europe’s annual flux. Our study was therefore able to identify the current and future major contributors to Gdanth flux in Europe and identify abrupt changes related to the COVID-19 pandemic.

Synthesizing MR Image Contrast Enhancement Using 3D High-Resolution ConvNets.

Gadolinium-based contrast agents (GBCAs) have been widely used to better visualize disease in brain magnetic resonance imaging (MRI). However, gadolinium deposition within the brain and body has raised safety concerns about the use of GBCAs. Therefore, the development of novel approaches that can decrease or even eliminate GBCA exposure while providing similar contrast information would be of significant use clinically. In this work, we present a deep learning based approach for contrast-enhanced T1 synthesis on brain tumor patients. A 3D high-resolution fully convolutional network (FCN), which maintains high resolution information through processing and aggregates multi-scale information in parallel, is designed to map pre-contrast MRI sequences to contrast-enhanced MRI sequences. Specifically, three pre-contrast MRI sequences, T1, T2 and apparent diffusion coefficient map (ADC), are utilized as inputs and the post-contrast T1 sequences are utilized as target output. To alleviate the data imbalance problem between normal tissues and the tumor regions, we introduce a local loss to improve the contribution of the tumor regions, which leads to better enhancement results on tumors. Extensive quantitative and visual assessments are performed, with our proposed model achieving a PSNR of 28.24 dB in the brain and 21.2 dB in tumor regions. Our results suggest the potential of substituting GBCAs with synthetic contrast images generated via deep learning.

Gadolinium deposition in the brain of patients with relapsing-remitting multiple sclerosis after 10 years of follow-up

Background/Aim. Since 2014 and the publication of the results of the first study on the accumulation of gadolinium contrast, we have witnessed a growing body of evidence on the deposition and retention of gadolinium in the brain after the use of gadolinium-based contrast agents (GBCAs). However, there is still no strong clinical evidence of the adverse effects of GBCAs on the brain parenchyma. The aim of the study was to determine the existence of gadolinium deposits in the brain of patients with relapsing-remitting multiple sclerosis after a ten-year follow-up period. During this period, the patients have regularly, each year, undergone magnetic resonance imaging (MRI) with the administration of gadolinium contrast (gadopentetate dimeglumine ? Magnevist?) in order to follow the course of the disease. Methods. A cohort of 20 patients was formed for the purpose of this study. The ratio of the values of the signal intensity (SI) of different regions of the brain-to-cerebrospinal fluid (CSF) was com-pared for each patient on the initial MRI examination and the MRI examination ten years later. Results. Frontal cortex-to-CSF (p &lt; 0.01), occipital cortex-to-CSF (p &lt; 0.01), the white matter of the corona radiata-to-CSF (p &lt; 0.01), parietal cortex-to-CSF (p &lt; 0.05), thalamus-to-CSF (p = 0.051), putamen-to-CSF (p = 0.06), and anterior and posterior limb of the capsula interna-to-CSF (p = 0.062) SI ratios increased after multiple gadopentetate administrations. An increase in the absolute values of the T1- weighted (T1W) signal in three-quarters of patients was registered in the frontal and occipital cortex and cerebellar hemispheres. A slightly smaller increase in SI, but still greater than 55?65%, was registered in structures of the parietal cortex, putamen, cornu anterior and posterior of the capsula interna, corpus callosum (CC) splenium, pons, thalamus, nucleus caudatus, substantia nigra, CC genu, and temporal cortex. Conclusion. In the cohort of 20 patients, there was a statistically significant increase in SI in the pre-contrast T1W sequence in the following structures: frontal, parietal, and occipital cortex, as well as supratentorial white matter. This result speaks in favor of the existence of chronic accumulation of gadolinium contrast agent gadopentetate dimeglumine in brain structures.

Utility of Gadolinium Use in the Imaging Follow-Up of Nonenhancing Primary Brain Neoplasms in Children.

Background and purpose Gadolinium-based contrast agents (GBCAs) have been administered clinically since 1988. They are remarkably well tolerated by children and result in dose-dependent tissue deposition, even in patients with normal renal function. No adverse effects of gadolinium deposition in patients with normal renal function have been established. Given the uncertain effects of gadolinium deposition, we sought to analyze gadolinium use in the imaging follow-up of nonenhancing primary brain neoplasms in children. Materials and methods This retrospective, institutional review board-approved and Health Insurance Portability and Accountability Act-compliant study evaluated pediatric patients who received GBCA in the routine evaluation of brain neoplasms. This special subset included 30 patients (<18 years old) with initially nonenhancing primary intracranial neoplasms who received treatment and follow-up at our institution. Patient data included sex, age from diagnosis to most recent imaging follow-up, number of contrast-enhanced magnetic resonance imaging (MRI) follow-up exams, and histopathology from a biopsy or resection. Results The group had an expected variety of tumors, including low-grade astrocytomas, dysembryoplastic neuroepithelial tumors, oligodendrogliomas, and teratomas. Half of our patients had tumors of unknown histopathology that were not biopsied or resected. The median age at diagnosis was 8.9 years, the median of four follow-up MRIs per patient, and the median follow-up time of four years. Only one of the 30 patients developed an enhancing focus on follow-up MRI that remained stable and asymptomatic over two years and did not require surgical intervention. Conclusion Judicious use of GBCA in children, especially when numerous exams over many years are anticipated, is advised given the data regarding soft-tissue deposition. Preliminary results suggest that it may be feasible to omit GBCA from routine follow-ups of initially nonenhancing brain neoplasms.

Risk of fetal or neonatal death or neonatal intensive care unit admission associated with gadolinium magnetic resonance imaging exposure during pregnancy

Concerns have been raised about prenatal exposure to magnetic resonance imaging with gadolinium-based contrast agents because of nonclinical findings of gadolinium retention in fetal tissue and 1 population-based study reporting an association with adverse pregnancy outcomes. This study aimed to evaluate the association between prenatal magnetic resonance imaging exposure with and without gadolinium-based contrast agents and fetal and neonatal death and neonatal intensive care unit admission. We constructed a retrospective cohort of >11 million Medicaid-covered pregnancies between 1999 and 2014 to evaluate the association between prenatal magnetic resonance imaging exposure with and without gadolinium-based contrast agents and fetal and neonatal death (primary endpoint) and neonatal intensive care unit admissions (secondary endpoint). Medicaid claims data were linked to medical records, Florida birth and fetal death records, and the National Death Index to validate the outcomes and gestational age estimates. Pregnancies with multiples, concurrent cancer, teratogenic drug exposure, magnetic resonance imaging focused on fetal or pelvic evaluation, undetermined gadolinium-based contrast agent use, or those preceded by or contemporaneous with congenital anomaly diagnoses were excluded. We adjusted for potential confounders with standardized mortality ratio weighting using propensity scores. Among 5991 qualifying pregnancies, we found 11 fetal or neonatal deaths in the gadolinium-based contrast agent magnetic resonance imaging group (1.4%) and 73 in the non-gadolinium-based contrast agent magnetic resonance imaging group (1.4%) with an adjusted relative risk of 0.73 (95% confidence interval, 0.34-1.55); the neonatal intensive care unit admission adjusted relative risk was 1.03 (0.76-1.39). Sensitivity analyses investigating the timing of magnetic resonance imaging or repeat magnetic resonance imaging exposure during pregnancy and simulating the impact of exposure misclassification corroborated these results. This study addressed the safety concerns related to prenatal exposure to gadolinium-based contrast agents used in magnetic resonance imaging and the risk thereof on fetal and neonatal death or the need for neonatal intensive care unit admission. Although the results on fatal or severe acute effects are reassuring, the impact on subacute outcomes was not evaluated.

Elemental Imaging of Long-term Gadolinium Retention in Rodent Femur.

Background The use of gadolinium-based contrast agents (GBCAs) is linked to gadolinium retention in the skeleton of healthy individuals. The mechanism of gadolinium incorporation into bone tissue is not fully understood and requires spatially resolved analysis to locate the gadolinium. Purpose To compare the quantitative distribution of gadolinium retained over time in rodent femur following the administration of gadodiamide and gadobutrol at three different time points. Materials and Methods In this animal study conducted between May 2018 and April 2020, 108 9-week-old healthy rats were repeatedly injected with either gadodiamide, gadobutrol, or saline solution and were killed 1, 3, or 12 months after the last injection. The femurs of six female and six male rats per each group and time point were collected. Quantitative elemental imaging of gadolinium in longitudinal thin sections was performed on one sample per sex with use of laser ablation inductively coupled plasma mass spectrometry (ICP-MS). Gadolinium concentration was determined with use of ICP-MS on the samples of all animals (six per group). Mann-Whitney U tests were applied on pairwise comparisons to determine potential sex effect and GBCA effect on gadolinium concentrations. Results The highest gadolinium retention was observed in the gadodiamide group (concentration, 97-200 nmol · g-1), exceeding the mean concentration in the gadobutrol group (6.5-17 nmol · g-1). However, the gadolinium distribution pattern was similar for both contrast agents, showing prominent gadolinium retention at endosteal surfaces, in the bone marrow, and in small tissue pores. Gadolinium distribution in cortical bone changed over time, initially showing a thin rim of higher concentration close to the periosteum, which appeared to grow wider and move toward the interior of the femur over 1 year. Conclusion For both gadolinium-based contrast agents, gadolinium retention in rat bone was initially located close to the periosteum and bone cavities and changed with bone remodeling processes. The relevance to long-term storage of gadolinium in humans remains to be determined. © RSNA, 2022 Online supplemental material is available for this article.

Gadolinium-based contrast agents for imaging of the central nervous system: A multicenter European prospective study.

Contrast-enhanced MR (CE-MR) imaging is required to improve lesion detection and characterization and to increase diagnostic confidence. This study aims to evaluate the safety, effectiveness, and usage patterns of recently introduced ClariscanTM (gadoterate meglumine) and other macrocyclic gadolinium-based contrast agents (GBCAs) used for magnetic resonance imaging (MRI) of the central nervous system (CNS). Data was obtained from a European multicenter, prospective, observational postmarketing study that included pediatric and adult patients undergoing contrast-enhanced MRI with a GBCA used in routine clinical practice. Safety data was collected by spontaneous patient adverse event (AE) reporting. Effectiveness was assessed via changes in radiological diagnosis, diagnostic confidence, and image quality. 766 patients with CNS-related indications were included from 8 centers across 5 European countries between December 2018 and November 2019. Clariscan (gadoterate meglumine) was used in 66% (503) of exams, Dotarem® (gadoterate meglumine) in 20% (160), Gadovist® (gadobutrol) in 13% (97), and ProHance® (gadoteridol) in 1%. GBCA use increased the diagnostic confidence in 95% (724/766) of patients and a change in radiological diagnosis in 65% (501/766) of patients. The Clariscan-specific data revealed an increase in diagnostic confidence in 94% (472/503) of patients and resulted in a change in radiological diagnosis in 58% (293/503) of patients. Image quality was considered excellent or good in 95% of patients across all GBCAs and in 94% of patients who received Clariscan. No AEs were reported in this cohort including Clariscan. This data demonstrates the excellent safety and efficacy profile of Clariscan and other GBCAs used in MRI examination of the CNS.