Systemic Fibrosis In Patients Research Articles

MRI Gadolinium-Based Contrast Media: Meeting Radiological, Clinical, and Environmental Needs.

Gadolinium-based contrast agents (GBCAs) are routinely used in magnetic resonance imaging (MRI). They are essential for choosing the most appropriate medical or surgical strategy for patients with serious pathologies, particularly in oncologic, inflammatory, and cardiovascular diseases. However, GBCAs have been associated with an increased risk of nephrogenic systemic fibrosis in patients with renal failure, as well as the possibility of deposition in the brain, bones, and other organs, even in patients with normal renal function. Research is underway to reduce the quantity of gadolinium injected, without compromising image quality and diagnosis. The next generation of GBCAs will enable a reduction in the gadolinium dose administered. Gadopiclenol is the first of this new generation of GBCAs, with high relaxivity, thus having the potential to reduce the gadolinium dose while maintaining good in vivo stability due to its macrocyclic structure. High-stability and high-relaxivity GBCAs will be one of the solutions for reducing the dose of gadolinium to be administered in clinical practice, while the development of new technologies, including optimization of MRI acquisitions, new contrast mechanisms, and artificial intelligence may help reduce the need for GBCAs. Future solutions may involve a combination of next-generation GBCAs and image-processing techniques to optimize diagnosis and treatment planning while minimizing exposure to gadolinium. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 3.

Capability of constructive interference in steady state sequence versus postcontrast T1-weighted imaging in cerebellopontine angle and internal auditory canal masses

Background: The tumor size is one of the main factors in the treatment of cerebellopontine angle (CPA) tumors, and magnetic resonance imaging (MRI) with gadolinium-based contrast agent (GBCA) provides the best evaluation. However, administration of the gadolinium is time consuming and increasing in cost. There is a risk of nephrogenic systemic fibrosis in patients with renal failure and liver or renal transplantation. Objective: The purpose of this study was to assess the capability of constructive interference in steady state (CISS) sequence in measuring the tumor size of the CPA and internal auditory canal (IAC) masses compared to postcontrast T1-weighted images (T1-WI). Materials and Methods: The 118 MR studies with both CISS sequence and postcontrast T1-WI of 45 patients with CPA and IAC masses were retrospectively reviewed. Results: There was no significant difference between CISS and postcontrast T1-WI in measuring size in transverse diameter of the masses (p = 0.051-0.06). The longitudinal diameter measurement revealed a significant difference (p < 0.001) and the measured size on postcontrast T1-WI was slightly larger than the CISS image. The difference in median measurement between two sequences was less than 0.9 mm. and Bland-Altman plots revealed that differences between the two sequences in longitudinal and transverse diameters of the masses were within the limits of agreement. Interobserver agreement showed excellent correlation (r = 0.994-0.999, p < 0.001 by Pearson's product-moment correlation). Conclusions: The CISS sequence may be sufficient for assessing the size of CPA and IAC masses, which can be used interchangeably with postcontrast T1-weighted image as a contrast-free option, especially in follow-up studies and vulnerable settings of gadolinium administration.

Radiographic Contrast Media and the Kidney.

AKI is a potential complication of intravascular iodinated contrast exposure. Contrast-associated AKI, which typically manifests as small and transient decrements in kidney function that develop within several days of contrast administration, is associated with serious adverse outcomes, including progressive kidney dysfunction and death. However, a causal link between the small increases in serum creatinine that characteristically occur with contrast-associated AKI and serious adverse outcomes remains unproven. This is important given mounting evidence that clinically indicated, potentially lifesaving radiographic procedures are underutilized in patients with CKD. This has been hypothesized to be related to provider concern about precipitating contrast-associated AKI. Intravascular gadolinium-based contrast, an alternative to iodinated contrast that is administered with magnetic resonance imaging, has also been linked with potential serious adverse events, notably the development of nephrogenic systemic fibrosis in patients with severe impairment in kidney function. Patients hospitalized in the intensive care unit frequently have clinical indications for diagnostic and therapeutic procedures that involve the intravascular administration of contrast media. Accordingly, critical care providers and others treating critically ill patients should possess a sound understanding of the risk factors for and incidence of such outcomes, the ability to perform evidence-based risk-benefit assessments regarding intravascular contrast administration, and knowledge of empirical data on the prevention of these iatrogenic complications.

Nephrogenic Systemic Fibrosis in Patients with Chronic Kidney Disease after the Use of Gadolinium-Based Contrast Agents: A Review for the Cardiovascular Imager.

Gadolinium-enhanced cardiac magnetic resonance has revolutionized cardiac imaging in the last two decades and has emerged as an essential and powerful tool for the characterization and treatment guidance of a wide range of cardiovascular diseases. However, due to the high prevalence of chronic renal dysfunction in patients with cardiovascular conditions, the risk of nephrogenic systemic fibrosis (NSF) after gadolinium exposure has been a permanent concern. Even though the newer macrocyclic agents have proven to be much safer in patients with chronic kidney disease and end-stage renal failure, clinicians must fully understand the clinical characteristics and risk factors of this devastating pathology and maintain a high degree of suspicion to prevent and recognize it. This review aimed to summarize the existing evidence regarding the physiopathology, clinical manifestations, diagnosis, and prevention of NSF related to the use of gadolinium-based contrast agents.

Gray-Scale, Color Doppler, Spectral Doppler, and Contrast-Enhanced Renal Artery Ultrasound: Imaging Techniques and Features.

Renal artery stenosis (RAS) is increasingly being detected in elderly patients as life expectancy increases. RAS induces hypertension or reduces renal function. Computed tomography or magnetic resonance angiography are objective in detecting RAS but may cause iodine-induced nephrotoxicity or nephrogenic systemic fibrosis in patients with RAS. Ultrasound (US) is, by contrast, a noninvasive and real-time imaging modality useful in patients with reduced renal function. Renal US is not as sensitive for detecting RAS because this technique indirectly assesses the renal artery by analyzing intrarenal hemodynamic changes. Although, ideally, US would be used to directly evaluate the renal artery, its current utility for RAS detection remains unclear. The purpose of this review is to introduce how to assess renal artery with US, to describe imaging features of renal artery US, to compare renal artery US and renal US, and to show how to perform work-up in patients in whom RAS is suspected.

Risk of nephrogenic systemic fibrosis in patients with impaired renal function undergoing fixed-dose gadoxetic acid-enhanced magnetic resonance imaging.

To assess the risk of nephrogenic systemic fibrosis (NSF) in patients with renal impairment undergoing gadoxetic acid-enhanced magnetic resonance imaging. This retrospective study included patients who had an estimated glomerular filtration rate (eGFR) below 60mL/min per 1.73m2 or had undergone dialysis around the time of gadoxetic acid exposure from January 2010 to November 2019. All patients received at least one intravenous injection of gadoxetic acid at a fixed dose of 2.5mmol. The primary endpoint was the development of NSF after exposure to gadoxetic acid based on Girardi's clinicopathological scoring system. A total of 204 patients with renal impairment received 424 injections of gadoxetic acid, of which 131 and 54 had an eGFR of 30-59 and < 30mL/min per 1.73m2, respectively, and 19 had undergone hemodialysis. Eighty-two patients received multiple injections, with 23 receiving five or more injections. The dose of each exposure ranged from 0.02 to 0.07mmol/kg and the cumulative doses ranged from 0.02 to 0.45mmol/kg. Thirty-three patients had concomitant Child-Pugh class B or C cirrhosis. No NSF was detected during follow-up (median 20months; range 6days to 111months). The upper bound of the 95% confidence interval for NSF risk was 2.2% and 1.1% per patient and examination, respectively. No NSF was detected in this study. However, it is premature to ascertain the risk of NSF using gadoxetic acid in patients with renal impairment and further studies are warranted.

Noncontrast Magnetic Resonance Angiography in the Era of Nephrogenic Systemic Fibrosis and Gadolinium Deposition.

Gadolinium-based contrast agents for clinical magnetic resonance imaging are overall safe. However, the discovery of nephrogenic systemic fibrosis in patients with severe renal impairment and gadolinium deposition in patients receiving contrast have generated developments in contrast-free imaging of the vasculature, that is, noncontrast magnetic resonance angiography. This article presents an update on noncontrast magnetic resonance angiography techniques, with comparison to other imaging alternatives. Potential benefits and challenges to implementation, and evidence to date for various clinical applications are discussed.

Risk of Nephrogenic Systemic Fibrosis in Stage 4 and 5 Chronic Kidney Disease Following Group II Gadolinium-based Contrast Agent Administration: Subanalysis by Chronic Kidney Disease Stage.

The risk of nephrogenic systemic fibrosis in patients with stage 4 or 5 chronic kidney disease (CKD) who receive a group II gadolinium-based contrast agent is very low, including in patients with e...

Current and Future MR Contrast Agents: Seeking a Better Chemical Stability and Relaxivity for Optimal Safety and Efficacy.

This review summarizes 30 years of experience in the development and clinical use of magnetic resonance (MR) contrast agents. Despite their undisputable usefulness for disease diagnosis, gadolinium (Gd)-based contrast agents (GBCAs) have gone through 2 major safety crises. Approximately 10 years ago, the regulatory agencies decided to restrict the use of GBCAs to minimize the risk of nephrogenic systemic fibrosis in patients with severe renal insufficiency. Yet, following the recent discovery of Gd retention in brain, the same agencies adopted different positions ranging from suspension of marketing authorizations, changes in GBCA safety labeling, and performing preclinical and clinical studies to assess the potential long-term consequences of Gd accumulation on motor and cognitive functions. Besides, magnetic resonance imaging (MRI) has benefited from MR technological advances, which provide alternative solutions to increase the MR signal, generate new contrasts on MRI scans, and accelerate their acquisition and analysis. Altogether, GBCAs in combination with new MR techniques have found their place in the diagnostic pathway of various diseases. Despite the large research efforts to identify and develop alternative Gd-free MR agents, manganese- and iron-based contrast agents have failed to reach market approval. In this context, the development of next-generation MR contrast agents should focus on high-stability and high-relaxivity GBCAs, such as gadopiclenol, which offer the possibility to adapt the administered Gd dose to each indication while ensuring an optimal patient safety.

Risk of Nephrogenic Systemic Fibrosis in Patients With Stage 4 or 5 Chronic Kidney Disease Receiving a Group II Gadolinium-Based Contrast Agent

Risk of nephrogenic systemic fibrosis (NSF) to individual patients with stage 4 or 5 chronic kidney disease (CKD; defined as estimated glomerular filtration rate of <30 mL/min/1.73 m2) who receive a group II gadolinium-based contrast agent (GBCA) is not well understood or summarized in the literature. To assess the pooled risk of NSF in patients with stage 4 or 5 CKD receiving a group II GBCA. A health sciences informationist searched the Ovid (MEDLINE and MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citation, and Daily and Versions), Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Open Grey databases from inception to January 29, 2019, yielding 2700 citations. Citations were screened for inclusion in a multistep process. Agreement for final cohort inclusion was determined by 2 blinded screeners using Cohen κ. Inclusion criteria consisted of stage 4 or 5 CKD with or without dialysis, administration of an unconfounded American College of Radiology classification group II GBCA (gadobenate dimeglumine, gadobutrol, gadoterate meglumine, or gadoteridol), and incident NSF as an outcome. Conference abstracts, retracted manuscripts, narrative reviews, editorials, case reports, and manuscripts not reporting total group II GBCA administrations were excluded. Data extraction was performed for all studies by a single investigator, including publication details, study design and time frame, patient characteristics, group II GBCA(s) administered, total exposures for patients with stage 4 or stage 5 CKD, total cases of unconfounded NSF, reason for GBCA administration, follow-up duration, loss to follow-up, basis for NSF screening, and diagnosis. Pooled incidence of NSF and the associated upper bound of a 2-sided 95% CI (risk estimate) for the pooled data and each of the 4 group II GBCAs. Sixteen unique studies with 4931 patients were included (κ = 0.68) in this systematic review and meta-analysis. The pooled incidence of NSF was 0 of 4931 (0%; upper bound of 95% CI, 0.07%). The upper bound varied owing to different sample sizes for gadobenate dimeglumine (0 of 3167; upper bound of 95% CI, 0.12%), gadoterate meglumine (0 of 1204; upper bound of 95% CI, 0.31%), gadobutrol (0 of 330; upper bound of 95% CI, 1.11%), and gadoteridol (0 of 230; upper bound of 95% CI, 1.59%). This study's findings suggest that the risk of NSF from group II GBCA administration in stage 4 or 5 CKD is likely less than 0.07%. The potential diagnostic harms of withholding group II GBCA for indicated examinations may outweigh the risk of NSF in this population. PROSPERO identifier: CRD42019123284.

Observational study on the incidence of nephrogenic systemic fibrosis in patients with renal impairment following gadoterate meglumine administration: the NSsaFe study.

Nephrogenic systemic fibrosis (NSF) is a rare life-threatening condition strongly associated with the administration of gadolinium-based contrast agents in patients with severe or endstage renal impairment. To prospectively determine the incidence of NSF in patients with renal impairment after administration of gadoterate meglumine. Prospective. In all, 540 patients with moderate, severe, or endstage renal impairment, scheduled to undergo a routine contrast-enhanced MRI with gadoterate meglumine. Mean age was 69.7 ± 12.7 years (range: 21-95) with 58.4% of males. 1.5T or 3.0T, sequence according to each site practice. Medical history, indication(s) for current MRI and adverse events were recorded for each patient. Patients were followed up over 2 years after administration with three visits separated by at least 3 months to detect any signs/symptoms suggestive of NSF. Descriptive. Renal impairment was graded as moderate for 69.4% of patients, severe for 16.0% and endstage for 12.1%; 2.6% had undergone a kidney transplant. Estimated glomerular filtration rate ranged from 4 to 59 mL/min/1.73 m2 except one value of 74 mL/min/1.73 m2 in a patient with kidney transplant. Central nervous system exploration was the main MRI indication (34.7%) and mean dose injected was 0.22 ± 0.09 mL/kg. Overall, 446 patients (82.6%) attended at least one follow-up visit and completed the NSF questionnaire and 329 (60.9%) attended the 2-year visit. No suspicion of NSF was reported in all 446 patients, including 119 patients with severe or endstage renal impairment. No deaths and no adverse events were reported during the MRI examination and the usual period of follow-up after gadoterate meglumine administration. No cases of NSF were observed in the 446 patients with moderate to endstage renal impairment followed up over a maximum of 2 years after injection of gadoterate meglumine. 2 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2020;51:607-614.

Effect of gadolinium concentration on temperature change under magnetic field.

Gadolinium based contrast agents (GBCAs) were found to play a role in nephrogenic systemic fibrosis in patients with and without renal impairment. Therefore, preserving the structural stability of GBCAs to reduce their propensity to liberate Gd3+ is of utmost importance. This study evaluates the effect of gadolinium concentration of GBCAs on solution temperature under magnetic fields. It is hypothesized that presence of gadolinium will lead to temperature changes of its solutions under magnetic field, and this change will depend on concentration. In this study, GBCAs were diluted to concentrations of 0.6, 1.2, 1.8, 2.4 mMol/L. A 10mL preparation in pure water, simulated body fluid (SBF), and plasma was scanned at 3T following a soft tissue neck protocol, and their temperatures were measured. Findings revealed that concentration of GBCA had significant effect on temperature change in all dilution media. Type of commercially available GBCA had an effect only in SFB and plasma. Evaluation of correlation between conditional stability constant (Kcond) and temperature difference (ΔT) revealed that in water and SBF there exists a positive correlation between Kcond and temperature variation. Collectively, GBCAs can cause local temperature variations when administered into patients, and can affect dissociation of gadolinium from its chelates, which should be investigated in a further study.

Gadolinium deposition and the potential for toxicological sequelae – A literature review of issues surrounding gadolinium‐based contrast agents

Every year, approximately 30 million magnetic resonance imaging scans are enhanced with gadolinium-based contrast agents (GBCAs) worldwide. Although the development of nephrogenic systemic fibrosis in patients with renal impairment is well-documented, over recent years it has become apparent that exposure to GBCAs can potentially result in gadolinium deposition within human bone and brain tissue even in the presence of normal renal function. This review will address some of the controversies surrounding the safety of GBCA administration based on evidence from in vivo experiments, animal studies and clinical studies. We additionally evaluate the potential risk of toxicity from exposure to gadolinium in light of new guidance published by the US Food and Drug Administration and the European Medicines Agency, and discuss whether gadolinium deposition disease exists as a new diagnosis.

Gadolinium as a new emerging contaminant of aquatic environments.

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.

No Incidence of Nephrogenic Systemic Fibrosis after Gadobenate Dimeglumine Administration in Patients Undergoing Dialysis or Those with Severe Chronic Kidney Disease

HomeRadiologyVol. 287, No. 1 PreviousNext CommunicationsFree AccessNotice of WithdrawalNo Incidence of Nephrogenic Systemic Fibrosis after Gadobenate Dimeglumine Administration in Patients Undergoing Dialysis or Those with Severe Chronic Kidney DiseaseMartin DR, Kalb B, Mittal AJ, Salman K, Vedantham S, Mittal PKMartin DR, Kalb B, Mittal AJ, Salman K, Vedantham S, Mittal PKMartin DRKalb BMittal AJSalman KVedantham SMittal PKPublished Online:Mar 20 2018https://doi.org/10.1148/radiol.2018184004MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In Martin DR, Kalb B, Mittal AJ, Salman K, Vedantham S, Mittal PK. No Incidence of Nephrogenic Systemic Fibrosis after Gadobenate Dimeglumine Administration in Patients Undergoing Dialysis or Those with Severe Chronic Kidney Disease. Radiology 2018:286(1):113–119. https://doi.org/10.1148/radiol.2017170102The authors have requested to withdraw the above manuscript from publication because the study was not conducted in full accordance with the relevant institutional IRB protocol.The companion editorial has also been withdrawn from publication by the authors, in conjunction with the withdrawal of the highlighted manuscript: Prince MR, Weinreb JC. MR imaging and gadolinium: reassessing the risk of nephrogenic systemic fibrosis in patients with severe renal disease. Radiology 2018:286(1):120–121. https://doi.org/10.1148/radiol.2017172255Article HistoryPublished online: Mar 20 2018Published in print: Apr 2018 FiguresReferencesRelatedDetailsAccompanying This ArticleNotice of Withdrawal: No Incidence of Nephrogenic Systemic Fibrosis after Gadobenate Dimeglumine Administration in Patients Undergoing Dialysis or Those with Severe Chronic Kidney DiseaseFeb 14 2010RadiologyNotice of Withdrawal: MR Imaging and Gadolinium: Reassessing the Risk of Nephrogenic Systemic Fibrosis in Patients with Severe Renal DiseaseFeb 14 2018RadiologyRecommended Articles Notice of Withdrawal: No Incidence of Nephrogenic Systemic Fibrosis after Gadobenate Dimeglumine Administration in Patients Undergoing Dialysis or Those with Severe Chronic Kidney DiseaseRadiology2010Volume: 286Issue: 1Adverse Events to the Gadolinium-based Contrast Agent Gadoxetic Acid: Systematic Review and Meta-AnalysisRadiology2020Volume: 297Issue: 3pp. 565-572Signal Intensity Changes at MRI Following GBCA Exposure: Incidental Finding or Cause for Concern?Radiology2020Volume: 296Issue: 1pp. 131-133Notice of Withdrawal: MR Imaging and Gadolinium: Reassessing the Risk of Nephrogenic Systemic Fibrosis in Patients with Severe Renal DiseaseRadiology2018Volume: 286Issue: 1Comparison of Human Tissue Gadolinium Retention and Elimination between Gadoteridol and GadobenateRadiology2021Volume: 300Issue: 3pp. 559-569See More RSNA Education Exhibits Practical Approaches and Updated Topics in Gadoxetate-Enhanced MR Imaging of the Liver: What the Radiologists Should KnowDigital Posters2019Gadolinium Deposition and NSF: Should I Be Worried?Digital Posters20182019 MRI Safety Updates for Radiologists: Are We Too Careful or Careless?Digital Posters2019 RSNA Case Collection Autosomal recessive polycystic kidney diseaseRSNA Case Collection2021Brown tumour of the hard palateRSNA Case Collection2020Chronic myocardial infarctionRSNA Case Collection2020 Vol. 287, No. 1 Metrics Altmetric Score PDF download

Notice of Withdrawal: MR Imaging and Gadolinium: Reassessing the Risk of Nephrogenic Systemic Fibrosis in Patients with Severe Renal Disease.

This editorial has been withdrawn from publication by the authors in conjunction with the withdrawal of the highlighted manuscript (see https://doi.org/10.1148/radiol.2017170102).

Revisiting the Pharmacokinetic Profiles of Gadolinium-Based Contrast Agents

Gadolinium-based contrast agents (GBCAs) have been used for years for magnetic resonance imaging examinations. Because of their rapid blood clearance, they were considered as very safe products until some of them were shown to induce nephrogenic systemic fibrosis in patients with renal failure and hypersignals on T1-weighted unenhanced brain scans of patients with normal renal function. To date, these adverse effects have been related almost exclusively to the use of low-stability linear agents, which are more prone to release free gadolinium. The aim of the present meta-analysis was to ascertain the existence of a deep compartment for gadolinium storage in the body and to assess whether all the GBCAs present the same toxicokinetic profile. Applying a systematic literature search methodology, all clinical and preclinical studies reporting time-dependent plasma concentrations and renal excretion data of gadolinium were identified and analyzed. Since the individual data were not available, the analysis focused on the average values per groups of subjects or animals, which had received a given GBCA at a given dose. The rate constants of the distribution phase (α), rapid elimination phase (β), and residual excretion phase (γ) of gadolinium were determined in each group from the plasma concentration (Cp) time curves and the relative urinary excretion rate (rER) time curves, taking the 2-hour time point as a reference. Moreover, as bone may represent a reservoir for long-term gadolinium accumulation and slow release into the blood stream, the time curves of the relative concentration in the bone (rCB) of Gd-labeled GBCAs in mice or rats were analyzed taking day 1 concentrations as a reference. The ratio of gadolinium concentrations in the bone marrow (CBM) as compared with the bone (CB) was also calculated. The relative urinary excretion rate (rER) plots revealed a prolonged residual excretion phase of gadolinium in healthy volunteers, consistent with the existence of a deep compartment of distribution for the GBCAs. The rate constant γ of gadoterate meglumine (0.107 hour) is 5 times higher than that of the linear agents (0.020 ± 0.008 hour), indicating a much faster blood clearance for the macrocyclic GBCA. Similar results were obtained in the preclinical studies. A strong correlation was shown between the γ values of the different products and their respective thermodynamic stability constants (Ktherm). Greater clearance rates of Gd from murine bone were also found after gadoterate meglumine or gadoteridol injection (0.131-0.184 day) than after administration of the linear agents (0.004-0.067 day). The concentrations of Gd in the bone marrow (CBM) from animals exposed to either gadoterate meglumine or gadodiamide are higher than those in the bone (CB) for at least 24 hours. Moreover, the ratio of concentrations (CBM/CB) at 4 hours is significantly lower with the former agent than the latter (1.9 vs 6.5, respectively). Using a nonconventional pharmacokinetic approach, we showed that gadoterate meglumine undergoes a much faster residual excretion from the body than the linear GBCAs, a process that seems related to the thermodynamic stability of the different chelates. Gadolinium dissociation occurs in vivo for some linear chelates, a mechanism that may explain their long-term retention and slow release from bone. Potential consequences in terms of bone toxicity warrant further investigations.

A novel blood-pooling MR contrast agent: Carboxymethyl-diethylaminoethyl dextran magnetite

Gadofosveset trisodium is available as a prolonged pooling vascular contrast agent for magnetic resonance imaging. As gadolinium (Gd)-based agents may increase the risk for nephrogenic systemic fibrosis in patients with severe renal insufficiency, the present study synthesized carboxymethyl-diethylaminoethyl dextran magnetite (CMEADM) particles as a blood-pooling, non-Gd‑based contrast agent. CMEADM particles carry a negative or positive charge due to the binding of amino and carboxyl groups to the hydroxyl group of dextran. The present study evaluated whether the degree of charge alters the blood‑pooling time. The evaluation was performed by injecting four groups of three Japanese white rabbits each with CMEADM‑, CMEADM2‑, CMEADM+ (surface charges:‑10.4, ‑41.0 and +9.6mV, respectively) or with ultrasmall superparamagnetic iron oxide (USPIO; ‑11.5mV). The relative signal intensity (SIrel) of each was calculated using the following formula: SIrel=(SI post‑contrast‑SI pre‑contrast/SI pre‑contrast)x100. Following injection with the CMEADMs, but not with USPIO, the invivo pooling time was prolonged to >300min. No significant differences were attributable to the electric charge among the CMEADM‑, CMEADM2‑ or and CMEADM+ particles when analyzed with analysis of variance and Tukey's HSD test. Taken together, all three differently‑charged CMEADM2 particles exhibited prolonged vascular enhancing effects, compared with the USPIO. The degree of charge of the contrast agents used in the present study did not result in alteration of the prolonged blood pooling time.

Gadolinium Deposition and Toxicity: A Global Concern

Gadolinium-based contrast agents (GBCAs) have been used since 1988 for magnetic resonance imaging. These agents were considered very safe and, excluding nephrogenic systemic fibrosis in patients with renal failure, no clinical entities were associated with its administration. Our purpose is to summarize gadolinium induced toxicity by reviewing the most recent literature in this subject. It was believed that GBCAs distribute rapidly in the extracellular volume after intravenous administration and eliminate rapidly, almost completely, via renal excretion. Currently, we know that this is not entirely true. Some GBCAs may be retained, undergo dechelation and induce gadolinium deposition in different tissues such as liver, bone or brain in patients with normal renal function. The retained gadolinium, whether dechelated and associated with different compounds or in its original formulation, may trigger gadolinium-related toxic effects. This potential toxicity became a global concern. This review summarizes the most recent published data regarding gadolinium deposition, possible clinical significance of gadolinium tissue retention and accumulation, strategies to limit gadolinium body burden and some future trends in this area.

Contrast-enhanced magnetic resonance venography in pediatric patients with chronic kidney disease: initial experience with ferumoxytol.

Ferumoxytol is an ultra-small superparamagnetic iron oxide (USPIO) particle that is FDA-approved for parenteral treatment of iron deficiency anemia in adults with chronic kidney disease. Because of the association between gadolinium-based contrast agents and nephrogenic systemic fibrosis in patients with severe chronic kidney disease, we sought to evaluate the diagnostic role of ferumoxytol-enhanced MR venography in children with chronic kidney disease. Twenty children underwent 22 high-resolution ferumoxytol-enhanced MR venography examinations at 3.0T. High-resolution 3-D contrast-enhanced imaging was performed at a minimum of 3 time points following injection of ferumoxytol at a total dose of 4mg/kg. Two blinded pediatric radiologists independently scored six named veins on ferumoxytol-enhanced MR venography examinations according to a three-point subjective score, where a score ≥2 was considered diagnostic. Additionally, all relevant venous structures in the included field of view were analyzed for occlusive or non-occlusive thrombosis, compression and presence of collaterals. All patients underwent ferumoxytol-enhanced MR venography successfully and without adverse event. The overall scores of the reviewing radiologists for all venous structures were 2.7-2.9. In all cases, the reviewers were confident basing their diagnoses on the ferumoxytol-enhanced MR venography findings. In 12 of 22 examinations, findings on follow-up imaging or invasive procedures were available to correlate with the findings on ferumoxytol-enhanced MR venography. There was complete concordance between the findings from follow-up imaging and invasive procedures with findings from ferumoxytol-enhanced MR venography. Ferumoxytol holds promise as a powerful alternative to gadolinium-based contrast agents for reliable, high-resolution MR venography in children with chronic kidney disease.