Use Of Gadolinium-based Contrast Agents Research Articles

Use of Radiocontrast Agents in CKD and ESRD.

Contrast exposure in a population with chronic kidney disease (CKD) requires additional consideration given the risk of contrast-induced nephropathy (CIN) after exposure to iodinated contrast as well as systemic injury with exposure to gadolinium-based contrast agents (GBCA). Strategies to avoid CIN, and manage patients after exposure, including extracorporeal removal of contrast media, may differ among an advanced CKD population as compared to a general population. There is strong evidence to support the use of isotonic volume expansion and the lowest dose of low-osmolar or iso-osmolar contrast media possible to decrease CIN. The current literature on other newer prophylactic strategies such as statins, remote ischemic preconditioning, discontinuation of renin angiotensin aldosterone system (RAAS) blockade, and RenalGuard is limited thus these strategies cannot currently be recommended as routine prophylaxis for CIN. The use of extracorporeal removal of contrast agents as prophylaxis to reduce CIN has been the subject of multiple studies; however, data do not support a beneficial effect in reduction in CIN. Immediate removal of contrast by dialysis in a maintenance dialysis population is also not recommended, unless an individual's cardiopulmonary status is dependent on strict volume management. In patients with reduced renal function, GCBA exposure increases the risk of NSF. In patients with AKI, CKD stage 3 or greater (eGFR <30ml/minute/1.73m2 ), or patients on dialysis, we do not recommend the use of GBCA and alternative imaging modalities should be considered. If patients absolutely need magnetic resonance imaging with GBCA, we recommend the use of the lowest dose possible of the newer macrocylic, ionic agents (gadoterate meglumine) as well as immediate postprocedural HD in patients already on HD or peritoneal dialysis or with stage 5 CKD and with a functioning dialysis access already in place.

Gadolinium based contrast agents in current practice: Risks of accumulation and toxicity in patients with normal renal function.

Despite being decked as the most prized compounds in the nugget box of contrast agents for clinical radiologists, and carrying an indisputable tag of safety of the US Food and Drug Administration for close to three decades, all may not be seemingly well with the family of gadolinium compounds. If the first signs of violations of primum non nocere in relation to gadolinium-based contrast agents (GBCAs) appeared in the millennium year with the first published report of skin fibrosis in patients with compromised renal function, the causal relationship between the development of nephrogenic systemic fibrosis (NSF) and GBCAs, first proposed by two European groups in 2006, further precluded their use in renocompromised patients. The toxicity, pharmacokinetics, and pharmacodynamics of GBCAs, however, has come under hawk-eyed scrutiny with recent reports that gadolinium tends to deposit cumulatively in the brain of patients with normal hepatobiliary function and intact blood–brain barrier. While the jury on the long-term hazard significance of this critical scientific finding is still out, the use of GBCAs must be guided by due clinical diligence, avoidance of repeated doses, and preferring GBCAs with the best safety profiles.

Potential Safety Issues Related to the Use of Gadolinium-based Contrast Agents.

This article reviews recent research on gadolinium deposit formation in the brain linked to contrast-enhanced MRI studies. Human and animal studies have confirmed the presence of gadolinium in the brain following the serial administration of gadolinium-based contrast agents. This is a relatively new and growing field of research primarily driven by concerns regarding unknown and potentially harmful side effects of gadolinium-based contrast agents. Retrospective observational in vivo studies in humans demonstrated T1 shortening effects in the brain parenchyma resulting from gadolinium exposure. These studies were followed by postmortem human and animal studies. Evidence exists that gadolinium may cause deposits in the brain and that this may occur independently of impaired renal function and in the presence of an intact blood-brain barrier. Gadolinium deposition has been linked primarily with the use of linear, rather than macrocyclic, gadolinium-based contrast agents. The formation of gadolinium deposits and its implications have been the focus of only a small number of research groups. The currently available data must be verified, and the potential factors that may be linked to this phenomenon and the clinical significance must be explored. Depending on future findings, changes in the clinical application of gadolinium-based contrast agents may be expected.

Anthropogenic gadolinium as a transient tracer for investigating river bank filtration

The growing use of gadolinium-based contrast agents in magnetic resonance imaging (MRI) leads to an increasing input of anthropogenic gadolinium (Gdanth) into natural environments. Conventional sewage treatment is unable to remove Gdanth and since MRI facilities are mainly used on weekdays the Gdanth inputs to sewage treatment plants are generally higher between Monday and Friday. This transient signal has been traced in both surface water and groundwater through 12-h composite samples collected at high spatial resolutions using depth-discrete rhizon samplers. Propagation of the Gdanth signal from surface water to groundwater was used to calibrate lumped parameter models. Transit time distributions derived for each sampling site revealed mean transit times of between 0.5 and 10days. Other metrics, such as peak transit time, were shown to correlate better with observed time lags between peak Gdanth concentrations in stream water and groundwater. The relatively stable artificial sweetener acesulfame was investigated as a possible additional sewage indicator, but decreasing concentrations along the flow path indicated its attenuation. We have demonstrated that the ideal tracer Gdanth occurs transiently and can be used to derive groundwater transit times.

Gadolinium deposition within the dentate nucleus and globus pallidus after repeated administrations of gadolinium-based contrast agents-current status.

Gadolinium-based contrast agents (GBCAs) have been used clinically since 1988 for contrast-enhanced magnetic resonance imaging (CE-MRI). Generally, GBCAs are considered to have an excellent safety profile. However, GBCA administration has been associated with increased occurrence of nephrogenic systemic fibrosis (NSF) in patients with severely compromised renal function, and several studies have shown evidence of gadolinium deposition in specific brain structures, the globus pallidus and dentate nucleus, in patients with normal renal function. Gadolinium deposition in the brain following repeated CE-MRI scans has been demonstrated in patients using T1-weighted unenhanced MRI and inductively coupled plasma mass spectroscopy. Additionally, rodent studies with controlled GBCA administration also resulted in neural gadolinium deposits. Repeated GBCA use is associated with gadolinium deposition in the brain. This is especially true with the use of less-stable, linear GBCAs. In spite of increasing evidence of gadolinium deposits in the brains of patients after multiple GBCA administrations, the clinical significance of these deposits continues to be unclear. Here, we discuss the current state of scientific evidence surrounding gadolinium deposition in the brain following GBCA use, and the potential clinical significance of gadolinium deposition. There is considerable need for further research, both to understand the mechanism by which gadolinium deposition in the brain occurs and how it affects the patients in which it occurs.

Gadolinium-Induced Fibrosis.

Gadolinium-based contrast agents (GBCAs), once believed to be safe for patients with renal disease, have been strongly associated with nephrogenic systemic fibrosis (NSF), a severe systemic fibrosing disorder that predominantly afflicts individuals with advanced renal dysfunction. We provide a historical perspective on the appearance and disappearance of NSF, including its initial recognition as a discrete clinical entity, its association with GBCA exposure, and the data supporting a causative relationship between GBCA exposure and NSF. On the basis of this body of evidence, we propose that the name gadolinium-induced fibrosis (GIF) more accurately reflects the totality of knowledge regarding this disease. Use of high-risk GBCAs, such as formulated gadodiamide, should be avoided in patients with renal disease. Restriction of GBCA use in this population has almost completely eradicated new cases of this debilitating condition. Emerging antifibrotic therapies may be useful for patients who suffer from GIF.

Towards MRI-guided cardiac ablation procedures with no contrast agent: safety and efficacy considerations

Background Efforts are underway to perform MRI-guided cardiac ablations in the magnet. The chief motivations are: 1) the ability to see the effects of treatment, 2) improved catheter positioning during mapping and therapy, and 3) avoiding ionizing radiation and iodinated contrast agent from x-ray. However, current efforts use gadolinium-based contrast agents (GBCAs) to obtain MR Angiogram (MRA) for anatomical context and late gadolinium enhancement (LGE) for enhancement of ablation lesions. There may be motivations to limit use of GBCAs, both in the specific context of an ablation procedure and in general use. The general use motivation is health-based, as the FDA is investigating the risk of gadolinium deposits in the brain after repeated use of GBCAs. Another motivation is for accuracy in assessment of acute lesions, since wash-in/out kinetics make it difficult to infer lesion size from enhancement regions in LGE images, even with carefully chosen timing and imaging parameters. The typical LGE protocol requires waiting 10-15 minutes after contrast agent injection before T1w imaging. This protocol is both unpractical to run repeatedly and limited by contrast-agent dose. It may be possible to perform this procedure without GBCAs. We focus on the acquisition of images for MRA, real-time navigation and lesion assessment. We present proof-of-concept data in swine left ventricle (LV).

Contrast Enhanced MRI in the Diagnosis of HCC.

Hepatocellular carcinoma (HCC) is the 6th most common cancer worldwide. Imaging plays a critical role in HCC screening and diagnosis. Initial screening of patients at risk for HCC is performed with ultrasound. Confirmation of HCC can then be obtained by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), due to the relatively high specificity of both techniques. This article will focus on reviewing MRI techniques for imaging HCC, felt by many to be the exam of choice for HCC diagnosis. MRI relies heavily upon the use of gadolinium-based contrast agents and while primarily extracellular gadolinium-based contrast agents are used, there is an emerging role of hepatobiliary contrast agents in HCC imaging. The use of other non-contrast enhanced MRI techniques for assessing HCC will also be discussed and these MRI strategies will be reviewed in the context of the pathophysiology of HCC to help understand the MR imaging appearance of HCC.

Guidelines for the Management of a Pregnant Trauma Patient.

Abstract Objective Physical trauma affects 1 in 12 pregnant women and has a major impact on maternal mortality and morbidity and on pregnancy outcome. A multidisciplinary approach is warranted to optimize outcome for both the mother and her fetus. The aim of this document is to provide the obstetric care provider with an evidence-based systematic approach to the pregnant trauma patient. Outcomes Significant health and economic outcomes considered in comparing alternative practices. Evidence Published literature was retrieved through searches of Medline, CINAHL, and The Cochrane Library from October 2007 to September 2013 using appropriate controlled vocabulary (e.g., pregnancy, Cesarean section, hypotension, domestic violence, shock) and key words (e.g., trauma, perimortem Cesarean, Kleihauer-Betke, supine hypotension, electrical shock). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English between January 1968 and September 2013. Searches were updated on a regular basis and incorporated in the guideline to February 2014. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technologyrelated agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). Benefits, harms, and costs This guideline is expected to facilitate optimal and uniform care for pregnancies complicated by trauma

Causal relationship between the use of gadolinium based contrast media and nephrogenic systemic fibrosis

Nephrogenic systemic fibrosis (NSF) is a severe iatrogenic disease that affect patients with impaired renal function exposed to gadolinium-based contrast agents. Clinically, symptoms develop within days or weeks after the exposure and mimic a scleromyxedema. The causal relationship between use of gadolinium-based contrast agents and NSF led to develop clinical guidelines aiming to limit the use of this contrast medium in high risk patients. These guidelines decreased the incidence of NSF in the last years. Unfortunately there is no specific treatment for NSF yet. Thus, strict adherence to current guidelines is key to prevent new cases. Renal dysfunction is increasingly common in our population. Therefore, practicing physicians should be aware of this potential complication of the use of gadolinium based contrast media.

High-resolution, whole-body vascular imaging with ferumoxytol as an alternative to gadolinium agents in a pediatric chronic kidney disease cohort

Exposure to gadolinium-based contrast agents (GBCA) in patients with chronic kidney disease (CKD) has been associated with the development of a potentially fatal disorder, nephrogenic systemic fibrosis (NSF). Although contrast-enhanced computed tomography (CT) is an alternative to magnetic resonance imaging (MRI), it carries the risk of radiation exposure and further reduction of residual renal function. Therefore we sought to assess the feasibility of ferumoxytol as an alternative to GBCA for contrast-enhanced MR angiography (MRA) in a pediatric cohort with CKD. Ferumoxytol is a parenteral iron supplement that contains ultrasmall superparamagnetic iron oxide (USPIO) and is a potent relaxivity agent for MRI. We describe the MRI findings in ten pediatric patients who needed detailed vascular mapping. Ferumoxytol (4mg/kg) was administered intravenously for contrast-enhanced MRA. The patients tolerated the procedure without complications. Resulting studies were highly diagnostic and were pivotal in guiding patient management. The images were notable for clear delineation of multiple vascular occlusions. Given the concerns associated with the use of GBCAs in renal failure, ferumoxytol is an excellent alternative contrast agent in pediatric end stage renal disease (ESRD) patients. Future studies are needed in order to further evaluate safety and efficacy of ferumoxytol in this patient population.

Incidence of Nephrogenic Systemic Fibrosis in Patients Undergoing Dialysis After Contrast-Enhanced Magnetic Resonance Imaging With Gadolinium-Based Contrast Agents

Nephrogenic systemic fibrosis (NSF) has been related to the use of gadolinium-based contrast agents (GBCAs) in patients undergoing dialysis. The Prospective Fibrose Nephrogénique Systémique study, a French prospective study supported by the French drug regulatory agency (Agence Nationale de Sécurité du Médicament) and the French Societies of Nephrology, Dermatology, and Radiology, aimed at determining the incidence of NSF in patients undergoing long-term dialysis. Adult patients undergoing long-term dialysis receiving a magnetic resonance imaging (MRI) examination prescribed between January 15, 2009 and May 31, 2011, with or without GBCA were included. The methodology was based on a patient form intended to detect any dermatological event (DE) that may occur within 4 months after the examination. Further investigations were planned with their physicians if a DE was reported. A total of 571 patients were included. A total of 50.3% received GBCA. Among them, 93.4% received a macrocyclic GBCA, usually gadoteric acid (88.9%). All in all, 22 patients (3.9%) reported a DE. Dermatological diagnoses did not reveal any evidence of NSF. The incidence of NSF after a single dose of a macrocyclic GBCA is null in our sample of 268 patients undergoing dialysis (hemodialysis and peritoneal dialysis). This incidence is just lower than 0.5%. When contrast-enhanced MRI can be essential, or even decisive, to the diagnosis, these results are important and reassuring if physicians need to perform contrast-enhanced MRI in patients undergoing dialysis.

Gadofosveset trisodium in coronary magnetic resonance angiography at 3 Tesla

Background Coronary magnetic resonance angiography (MRA) at 3T suffers from imaging inconsistencies compared to 1.5T despite the use of gadolinium-based contrast agents (GBCAs). Gadofosveset Trisodium (Ablavar ® ,L antheus Medical Imaging), with its high relaxivity and long intravascular residence time, offers greater potential over standard GBCAs to improve evaluation of the coronary arteries. Compared to its validation in larger arteries, the optimum dosage for coronary MRA has yet to be assessed. The purpose of the study was to evaluate the diagnostic potential of a 0.06 mmol/kg dose of Gadofosveset compared to a standard clinical dose of 0.03 mmol/kg, using a free-breathing whole-heart coronary MRA protocol with 1.0 mm3 spatial resolution and 100% navigator efficiency. The injection protocol was optimized for the prolonged pharmacokinetics of Gadofosveset. Methods Twenty two contrast enhanced CMR scans were performed in 11 subjects [2 (18.2%) male; 27.3 ± 6 years; BMI = 23.1 ± 3 kg/m2] on a 3.0T Verio Siemens scanner, using

Gadolinium and nephrogenic systemic fibrosis: an update

Nephrogenic systemic fibrosis (NSF) is a multisystem disease seen exclusively in patients with renal impairment. It can be severely debilitating and sometimes fatal. There is a strong association with gadolinium-based contrast agents used in magnetic resonance imaging (MRI). Risk factors include renal impairment and proinflammatory conditions, e.g. major surgery and vascular events. Although there is no single effective treatment for NSF, the most successful outcomes are seen following restoration of renal function, either following recovery from acute kidney injury or following renal transplantation. There have been ten biopsy-proved pediatric cases of NSF, with no convincing evidence that children have a significantly altered risk compared with the adult population. After implementation of guidelines restricting the use of gadolinium-based contrast agents in at-risk patients, there has been a sharp reduction in new cases and no new reports in children. Continued vigilance is recommended: screening for renal impairment, use of more stable gadolinium chelates, consideration of non-contrast-enhanced MRI or alternative imaging modalities where appropriate.

Gadolinium-based contrast agents: What does “single-dose” mean anymore?

Gadolinium-based contrast agents: What does “single-dose” mean anymore?

Nephrogenic systemic fibrosis (NSF) and gadolinium-based contrast media

Nephrogenic systemic fibrosis (NSF), unknown before March 1997 and first described in 2000, is a systemic disorder characterised by widespread tissue fibrosis. The first known case occurred in 1997, after the use of gadolinium-based contrast agents (GBCAs) at high doses in patients with renal failure had become routine. An overwhelming majority occurred within weeks to months after injection of a GBCA. This note comprises guidelines on the prevention of NSF.

Nephrogenic systemic fibrosis (NSF) and gadolinium-based contrast media

Nephrogenic systemic fibrosis (NSF), unknown before March 1997 and first described in 2000, is a systemic disorder characterised by widespread tissue fibrosis. The first known case occurred in 1997, after the use of gadolinium-based contrast agents (GBCAs) at high doses in patients with renal failure had become routine. An overwhelming majority occurred within weeks to months after injection of a GBCA. This note comprises guidelines on the prevention of NSF.

Safety of Gadopentetate Dimeglumine after 120 Million Administrations over 25 Years of Clinical Use

We evaluated the safety of gadopentetate dimeglumine (Gd-DTPA), the first contrast agent for magnetic resonance imaging, using pharmacovigilance data for spontaneously reported adverse events (AEs) after 120 million cumulative administrations worldwide. We analyzed spontaneously reported AEs for Gd-DTPA for pre-specified time periods between 1988 and 2011. Since the market introduction of Gd-DTPA in 1988, its global utilization reached 120 million cumulative administrations in 2011, more than 80% of which was by the USA, countries in the European Union (EU), and Japan. The global AE reporting rate was 21.2 in 100,000 administrations in 1988 and 14.4 in 100,000 administrations by 2011. Regional differences included higher reporting rates in the USA and Japan, and reporting rates lower than global rates in the EU. The reported rate of global serious AEs changed from 1.4 in 100,000 administrations in 1988 to 4.0 in 100,000 administrations in 2011. The highest number of reports of nephrogenic systemic fibrosis (NSF) was received from 2006 to 2008. Since 2009, no report of a current onset of NSF has been received. The reduced report rate of NSF may be due to increased awareness about the use of gadolinium-based contrast agents (GBCAs). After more than 120 million cumulative administrations, Gd-DTPA is a widely used GBCA that shows a consistently low and stable incidence of AEs.

Application of Gadolinium-Based Contrast Agents and Prevalence of Nephrogenic Systemic Fibrosis in a Cohort of End-Stage Renal Disease Patients on Hemodialysis

Background/Aims: Nephrogenic systemic fibrosis (NSF) is a highly debilitating disease that can occur in patients with reduced kidney function after application of gadolinium-based contrast agents (GBCA). In recent years, the incidence of the disease has significantly decreased. The aim of this study was to assess the prevalence of NSF in a cohort of dialysis patients and to investigate whether the use of GBCA has changed in this patient cohort. Methods: We studied 508 dialysis patients from 8 centers in the Ruhr area, Germany. Patients were visited during dialysis, and anamnestic data were collected by interview, from patient files and, if necessary, from radiological institutes. Patients were examined for cutaneous changes of NSF, which were defined using a scoring system based on hyperpigmentation, hardening, and tethering of skin of the extremities. Results: 4/508 patients were clinically suspected of NSF, yet only 2 had received GBCA and their diagnosis was confirmed dermatohistologically (0.4%). The other 2 had not received GBCA, and hence NSF was not suspected. Between 2006 and 2010, 49/508 patients underwent an MRI. 25/49 patients received GBCA. The relative proportion of MRIs with GBCA was highest in 2006 (9/13; 69.2%) and lowest in 2009 (6/16; 37.5%). The proportion of linear chelates (gadodiamide and gadopentetate dimeglumine) was highest in 2006 (8/9; 88.9%) and lower thereafter. Conclusion: The prevalence of NSF in our cohort of dialysis patients is very low. This may be the consequence of a progressively restricted use of GBCA in patients with impaired kidney function and a more widespread application of macrocyclic chelates.

Quantification of the Plasma Clearance Kinetics of a Gadolinium-Based Contrast Agent by Photoinduced Triplet Harvesting

The use of gadolinium-based contrast agents (GBCA) is integral to the field of diagnostic magnetic resonance imaging (MRI). Pharmacokinetic evaluation of the plasma clearance of GBCA is required for all new agents or improved formulations, to address concerns over toxicity or unforeseen side effects. Current methods to measure GBCA in plasma lack either a rapid readout or the sensitivity to measure small samples or require extensive processing of plasma, all obstacles in the development and characterization of new GBCA. Here, we quantify the plasma concentration of a labeled analogue of a common clinical GBCA by ligand triplet harvesting and energy transfer. The nonemittive GBCA becomes a "dark donor" to a fluorescent detector molecule, with a lower limit of detection of 10(-7) M in unprocessed plasma. On a time scale of minutes, we determine the plasma clearance rate in the wild-type mouse, using time-resolved fluorescence on a standard laboratory plate reader.