Gadolinium-based Contrast Agents In Patients Research Articles

Assessing Perfusion in Steno-Occlusive Cerebrovascular Disease Using Transient Hypoxia-Induced Deoxyhemoglobin as a Dynamic Susceptibility Contrast Agent.

Resting brain tissue perfusion in cerebral steno-occlusive vascular disease can be assessed by MR imaging using gadolinium-based susceptibility contrast agents. Recently, transient hypoxia-induced deoxyhemoglobin has been investigated as a noninvasive MR imaging contrast agent. Here we present a comparison of resting perfusion metrics using transient hypoxia-induced deoxyhemoglobin and gadolinium-based contrast agents in patients with known cerebrovascular steno-occlusive disease. Twelve patients with steno-occlusive disease underwent DSC MR imaging using a standard bolus of gadolinium-based contrast agent compared with transient hypoxia-induced deoxyhemoglobin generated in the lungs using an automated gas blender. A conventional multi-slice 2D gradient echo sequence was used to acquire the perfusion data and analyzed using a standard tracer kinetic model. MTT, relative CBF, and relative CBV maps were generated and compared between contrast agents. The spatial distributions of the perfusion metrics generated with both contrast agents were consistent. Perfusion metrics in GM and WM were not statistically different except for WM MTT. Cerebral perfusion metrics generated with noninvasive transient hypoxia-induced changes in deoxyhemoglobin are very similar to those generated using a gadolinium-based contrast agent in patients with cerebrovascular steno-occlusive disease.

MRI findings of iatrogenic extravasation of gadolinium-based contrast agents in patients with cancer.

Magnetic resonance imaging (MRI) findings after subcutaneous extravasation of gadolinium-based contrast agent (GBCA) have not been investigated in detail. To present the MRI findings of iatrogenic extravasation and to evaluate the characteristic findings. In this retrospective study of 16,039 patients with cancer, 11 patients had significant extravasation of macrocyclic GBCA, and 7 of the 11 had MRI of the injection site. Characteristic MRI findings as well as symptoms and changes over time were evaluated. The forearms or antecubital fossa felt cold in all seven cases, and 3 (43%) patients felt pain at the injection sites. Fat-suppressed T1-weighted images showed a mosaic pattern of the extravasate with mixed high and low signal in the subcutaneous tissue in 7 (100%) cases. Contrast enhancement of the fascia toward the proximal portion was observed in 3 (43%) cases. There was no subfascial deep extension. On T2-weighted images, GBCAs were observed as low-signal fluid collection on the fascia, with linear spread to the dermis and subcutaneous tissue. Four patients underwent daily MRI scans, all of whom had their contrast disappeared within three days. Macrocyclic GBCA disappears from subcutaneous tissue quickly after extravasation and is unlikely to cause serious sequelae.

Absence of T1 Hyperintensity in the Brain of Thalassemia Patients after Multiple Administrations of Gadobutrol

Gadolinium based contrast agents (GBCA) are used in magnetic resonance imaging (MRI) in order to improve the detection and the characterization of pathophysiologic processes. Many studies have reported an association between increased signal intensities (SI) on unenhanced T1-weighted MRI images in different brain regions and the history of repeated intravenous administrations of GBCAs in patients with normal renal function. We conducted a prospective study aimed to evaluate signal changes in the dentate nucleus (DN), globus pallidus (GP), pons, and thalamus (normalized to the deep cerebellum white matter) in T1-MRI images after serial injections of Gadobutrol for the study of the heart in patients with thalassemia.Among the thalassemic patients who underwent a brain MRI within a pilot study for iron overload assessment, we selected two groups of patients: 15 patients transfused and chelated with≥4 Gadobutrol administrations at a high dose (0.2 mmol/Kg per scan) and 8 thalassemia patients who never received Gadobutrol. Moreover, we included 13 healthy subjects who never received Gadobutrol as control group. Iron overload was assessed by the T2* technique.Signal intensity (SI) ratios in all regions were comparable among the three groups (see Table) and were not correlated with the number of Gadobutol administrations. No correlation was detected between SI ratios and T2* values.It is important to underline that thalassemia patients represent an high-risk population for the GBCA accumulation, due to the fact that, in presence of siderosis, ferric ions can compete with Gadolinium ions for the ligand, destabilizing the gadolinium complex. Nevertheless, our study describes the lack of increased SI after repeated administration of Gadobutrol, a nonionic macrocyclic agent. All our patients were chelated when they received the GBCA. Different studies showed the ability of all three iron chelators to chelate other metals. So, a potential role of chelation therapy may be supposed. [Display omitted] DisclosuresPepe:Chiesi Farmaceutici and ApoPharma Inc.: Other: Alessia Pepe is the PI of the MIOT project, that receives no profit support from Chiesi Farmaceutici S.p.A. and ApoPharma Inc.

Empiric Switching of Gadolinium-Based Contrast Agents in Patients With History of Previous Immediate Hypersensitivity Reaction to GBCA: A Prospective Single-Center, Single-Arm Efficacy Trial.

Breakthrough hypersensitivity reactions (HRs) to gadolinium-based contrast agent (GBCA) occur in 40% of patients despite corticosteroid premedication. Other strategies to reduce HRs are not well studied. The aim of this study was to prospectively evaluate HR rate to GBCA among patients with history of HR to GBCA, empirically given an alternative GBCA prior to repeat administration. From September 2019 to September 2020, patients with prior HR to GBCA received 13-hour oral corticosteroid and diphenhydramine premedication prescription with switching of GBCA to gadoterate (previously unavailable at our institution before September 2019). Power analysis (α error, 0.05; β error, 0.80) determined 21 patients were required. Patients were evaluated under a quality assurance waiver from the institutional review board. A radiologist documented the nature of initial HR and inciting GBCA, premedication received, incidence, and severity of breakthrough HR. After exclusions, we evaluated 26 patients with mild (92.3% [24/26]) or moderate (7.7% [2/26]) HR to gadobutrol (53.8% [14/26]), gadoxetate (3.8% [1/26]), and gadopentetate (3.8% [1/26]). In 38.5% (10/26), inciting GBCA was unknown but was likely gadobutrol or gadopentetate based on availability. There were 22 females. The mean patient age was 52.1 ± 15.8 years.From 27 gadoterate administrations, 59.3% (16/27) patients received corticosteroid and diphenhydramine premedication, 11.1% (3/27) received only diphenhydramine, and 29.6% (8/27) with no premedication.Hypersensitivity reaction rate after empiric switching to gadoterate was 3.7% (1 mild reaction; 95% confidence interval [CI], 0.09%-18.9%) overall with no difference in patients with (6.3% [1/16]; 95% CI, 0.15%-28.7%) or without (0%; [0/11] upper bound 95% CI, 25.0%) corticosteroid premedication. In this prospective single-arm study, empirically switching GBCA to gadoterate in patients with prior HR to GBCA substantially reduced the expected rate of subsequent HRs in patients with and without the use of corticosteroid premedication. Empirically switching GBCAs, with or without the use of corticosteroid premedication, can substantially reduce the rate of hypersensitivity breakthrough reactions.

Safety of Off-Label Use of Ferumoxtyol as a Contrast Agent for MRI: A Systematic Review and Meta-Analysis of Adverse Events.

Ferumoxytol has been studied as an alternative to gadolinium-based MRI contrast agents, but regulatory body warnings currently limit its use. Estimate the adverse event rate in patients undergoing MRI with ferumoxytol as a contrast agent. Systematic review. Thirty-nine studies including 5411 ferumoxytol administrations in 4336 patients. Multiple databases were searched for studies using ferumoxytol as an off-label MRI contrast agent in any patient population as of April 2020. Studies were eligible for inclusion if they reported the number and severity of adverse events (classified by American College of Radiology [ACR] severity of acute reactions). Risk of bias was assessed using the ROBINS-I tool. The proportion of administrations with adverse events was calculated using random effects meta-analysis of proportions. No deaths related to ferumoxytol administration were reported. Sixteen studies reported immediate adverse events in 3849 patients undergoing 4901 ferumoxytol administrations. Ninety-seven immediate adverse events were reported and the pooled adverse event proportion for immediate adverse events was 0.02 (95% confidence interval [CI] 0.02-0.02). Twenty-three studies reported time-unspecified adverse events in 487 patients undergoing 510 ferumoxytol administrations. Five time-unspecified adverse events were reported; the pooled adverse event proportion for time-unspecified adverse events was 0.01 (95% CI 0.00-0.04). 88% of adverse events were mild (90/102), 11% (11/102) were moderate, and 1% (1/102) was severe. Sixteen studies were at low risk of bias, 23 studies were at serious risk of bias. Subgroup analysis by patient population revealed no significant variability (adult vs. pediatric). No studies evaluated the use of ferumoxytol as an alternative to patients who had a prior hypersensitivity reaction to gadolinium-based contrast agents (GBCAs). The overall adverse event rate for off-label ferumoxytol use as an MRI contrast agent is 2%, with rare severe reactions and no deaths. To date, there are no studies evaluating the safety of ferumoxytol as an alternative to GBCAs in patients with a prior hypersensitivity reaction. 2 TECHNICAL EFFICACY STAGE: 5.

Establishing Reference Intervals for Gadolinium Concentrations in Blood, Plasma, and Urine in Individuals Not Previously Exposed to Gadolinium-Based Contrast Agents.

Over the recent years, there have been increasing concerns that exposure to gadolinium-based contrast agents (GBCAs) may be associated with retention of Gd within the skin, bones, and solid organs in patients with normal renal function, although the clinical implications of this deposition remain to be established. There are no published data available to guide the development of reference intervals for Gd concentrations in biological samples from healthy people. The aims of this study were to (1) determine whether healthy individuals who have not received GBCAs have detectable concentrations of Gd in their blood and urine, and (2) to develop a reference range for Gd concentrations in blood and spot urine samples for healthy individuals. Whole blood, plasma, and spot urine samples were taken from 120 healthy volunteers with estimated glomerular filtration rate 70 mL/min per 1.73 m or greater. Gd concentrations were measured in these samples using inductively coupled plasma mass-spectrometry. The reference intervals for Gd concentrations in whole blood, plasma, and urine were estimated as the 2.5th percentile and the upper reference limit as the 97.5th percentile. Ten (8.33%) of the 120 subjects had detectable concentrations of Gd in their whole blood (n = 5) or spot urine (n = 5) samples; no subjects had detectable concentrations of Gd in their plasma samples. Our proposed reference intervals for Gd are as follows: whole blood, <0.008 ng/mL or <0.050 nmol/L; plasma, <0.009 ng/mL or <0.057 nmol/L; spot urine, <0.036 μg/g or <0.0250 nmol/mmol. The results of this study provide reference intervals for whole blood, plasma, and urine Gd concentrations in healthy subjects who have not previously received GBCAs and will assist clinicians in assessing patients who have concerns regarding potential Gd retention postexposure and help guide further clinical studies to explore the pharmacokinetics of GBCAs in patients with normal renal function.

Two Non-gadolinium-based, Innovative Approaches to Preoperative Lymphangiography.

Summary:Most magnetic resonance lymphangiography techniques employ intravenous gadolinium-based contrast agents, which carry a US Food and Drug Administration warning about gadolinium retention in the body when used intravenously. Because of this, there may be reluctance to perform intradermal injections of gadolinium-based contrast agents in patients with obstructed lymphatic drainage due to concerns about gadolinium retention in the skin and soft tissues and potential-related toxicity. The aim of this study was to show proof of concept of 2 preoperative lymphangiographic techniques that do not use gadolinium-based contrast agents. One technique used contrast-enhanced ultrasound with intradermal injections of microbubbles (Lumason) in a patient with stage 3, nonpitting left upper extremity edema. Another technique used magnetic resonance imaging with intradermal injections of 0.03 mg/mL or 0.003% ferumoxytol (Feraheme) in a patient with stage 3, nonpitting right lower extremity edema. Both contrast-enhanced ultrasound with microbubbles and magnetic resonance lymphangiogram with ferumoxytol were able to identify candidates for lymphovenous bypass surgery. These candidates were not identified by conventional indocyanine green injections. The authors conclude that (1) low-dose ferumoxytol is a potentially effective non-gadolinium–based contrast alternative to gadolinium-based contrast agent in magnetic resonance lymphangiography and (2) contrast-enhanced ultrasound can identify candidate lymphatic vessels for anastomosis.

Safety of Gadolinium-Based Contrast Agents in Patients with Stage 4 and 5 Chronic Kidney Disease: a Radiologist's Perspective.

Gadolinium-based contrast agents (GBCAs) have been used for contrast-enhanced magnetic resonance imaging (MRI) since 1988 with >450 million intravenous GBCA doses administered worldwide and overall have had an excellent safety record (1,2). Numerous studies have demonstrated the benefit of GBCAs for a variety of diagnostic indications including improving sensitivity and specificity for malignancy, demyelination, central nervous system malignancy, and infection (3⇓⇓⇓–7). Initially, it was thought that GBCAs would be safer than iodinated contrast media for patients with kidney disease because they are less nephrotoxic at clinically administered doses (8). Although some case reports have linked AKI to GBCA administration, most cases involve patients with advanced renal disease or diabetes and with doses that exceed US Food and Drug Administration (FDA) recommendations (8). The safety of GBCAs in patients with kidney disease came into question in 2006 when a strong association was found between the use of GBCAs in patients with severe kidney disease and the development of nephrogenic systemic fibrosis (NSF) (9⇓–11). NSF results in fibrosis of the skin and internal organs and can be fatal. A conclusive mechanism of causation for NSF has not been determined. Several mouse models of NSF have been developed to investigate the underlying pathophysiology; however, they tend to use doses which are higher than those approved by the FDA and older linear agents (12⇓–14). A confounding issue is that many people with severe kidney disease received multiple exposures to GBCAs and did not develop NSF. Conversely, patients with only one administration of a GBCA have developed NSF (15,16). It is unclear if this could at least partially relate to interspecies differences. Multiple factors may contribute, most notably patient-specific risk factors and the stability of the GBCA, which is …

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.

Can Virtual Contrast Enhancement in Brain MRI Replace Gadolinium?: A Feasibility Study.

Gadolinium-based contrast agents (GBCAs) have become an integral part in daily clinical decision making in the last 3 decades. However, there is a broad consensus that GBCAs should be exclusively used if no contrast-free magnetic resonance imaging (MRI) technique is available to reduce the amount of applied GBCAs in patients. In the current study, we investigate the possibility of predicting contrast enhancement from noncontrast multiparametric brain MRI scans using a deep-learning (DL) architecture. A Bayesian DL architecture for the prediction of virtual contrast enhancement was developed using 10-channel multiparametric MRI data acquired before GBCA application. The model was quantitatively and qualitatively evaluated on 116 data sets from glioma patients and healthy subjects by comparing the virtual contrast enhancement maps to the ground truth contrast-enhanced T1-weighted imaging. Subjects were split in 3 different groups: enhancing tumors (n = 47), nonenhancing tumors (n = 39), and patients without pathologic changes (n = 30). The tumor regions were segmented for a detailed analysis of subregions. The influence of the different MRI sequences was determined. Quantitative results of the virtual contrast enhancement yielded a sensitivity of 91.8% and a specificity of 91.2%. T2-weighted imaging, followed by diffusion-weighted imaging, was the most influential sequence for the prediction of virtual contrast enhancement. Analysis of the whole brain showed a mean area under the curve of 0.969 ± 0.019, a peak signal-to-noise ratio of 22.967 ± 1.162 dB, and a structural similarity index of 0.872 ± 0.031. Enhancing and nonenhancing tumor subregions performed worse (except for the peak signal-to-noise ratio of the nonenhancing tumors). The qualitative evaluation by 2 raters using a 4-point Likert scale showed good to excellent (3-4) results for 91.5% of the enhancing and 92.3% of the nonenhancing gliomas. However, despite the good scores and ratings, there were visual deviations between the virtual contrast maps and the ground truth, including a more blurry, less nodular-like ring enhancement, few low-contrast false-positive enhancements of nonenhancing gliomas, and a tendency to omit smaller vessels. These "features" were also exploited by 2 trained radiologists when performing a Turing test, allowing them to discriminate between real and virtual contrast-enhanced images in 80% and 90% of the cases, respectively. The introduced model for virtual gadolinium enhancement demonstrates a very good quantitative and qualitative performance. Future systematic studies in larger patient collectives with varying neurological disorders need to evaluate if the introduced virtual contrast enhancement might reduce GBCA exposure in clinical practice.

Use and Safety of Gadolinium Based Contrast Agents in Pediatric MR Imaging.

Gadolinium-based contrast agents (GBCA) used for MR imaging are a valuable imaging resource that has benefited patient management over last three decades and largely have a high safety profile. However, recently, adverse effects related to GBCA like nephrogenic systemic fibrosis (NSF) and asymptomatic gadolinium deposition in tissues including brain are concerning. While NSF has largely stopped occurring due to precautions and guidelines to not use GBCA in patients with poor renal function, the long term effects of gadolinium deposition, especially in brain, are not known at this stage. Cautious approach needs to be taken with risk-benefit analysis in each patient to avoid its administration when not necessary. In this review, authors discuss basics of gadolinium, mechanism of enhancement, agents in clinical use and safety issues, and in the end, offer some solutions for safety concerns.

Physicians' awareness of gadolinium retention and MRI timing practices in the longitudinal management of pituitary tumors: a "Pituitary Society" survey.

In view of mounting attention related to possible brain retention of gadolinium-based contrast agents (GBCAs) in patients with normal renal function, our purpose was to detail results from a survey of pituitary experts to assess: 1) the timing interval and frequency of pituitary magnetic resonance imaging (MRI) following surgical and/or medical and/or radiation therapy of pituitary tumors, 2) awareness of the types of GBCAs used and their possible safety issues. The Pituitary Society Education Committee composed a survey with 12 multiple choice questions, 8 of which specifically addressed the time interval and frequency of MRI in the longitudinal management of pituitary tumors. The survey was distributed at two meetings; the International Pituitary Neurosurgeons Society conference in San Diego, CA, on February 18th, 2018, and the Pituitary Society Membership and Career Development Forum, Chicago, IL on March 18th, 2018. There is consensus among pituitary endocrinologists and neurosurgeons that long-term repeated imaging is recommended in most pituitary tumors, although the precise strategy of timing varied depending on the specialist group and the specific clinical context of the adenoma. The data also suggest that International Pituitary Neurosurgeons Society neurosurgeons, as well as Pituitary Society neuroendocrinologists, are sometimes unaware of which contrast agents are used by their institution, and many are also unaware that evidence of long-term brain retention has been reported with the use of GBCAs in patients with normal function. International pituitary endocrinologists and pituitary neurosurgeons experts suggest ongoing MRIs for the management of pituitary tumors; strategies vary based on clinical context, but also on individual experience and practice.

The Impact of Excess Ligand on the Retention of Nonionic, Linear Gadolinium-Based Contrast Agents in Patients With Various Levels of Renal Dysfunction: A Review and Simulation Analysis

The role of gadolinium (Gd)-based contrast agents (GBCAs) in the pathophysiology of nephrogenic systemic fibrosis (NSF) is now uncontested. Although the definitive mechanism has not been established, the association with weaker GBCA ligands and with reduced renal clearance supports a hypothesis that Gd release from the GBCAs is a key process in precipitating the disease. Prevention strategies often include the use of more stable GBCA ligands in patients with reduced kidney function, but animal models and some clinical data suggest that better patient outcomes can be achieved when excess ligand is administered with weaker GBCAs; this is particularly significant for OptiMARK, which contains a nonionic, linear ligand similar to gadodiamide, the active ingredient in Omniscan, but contains twice the amount of excess ligand. Here we review evidence regarding the use of OptiMARK over Omniscan for prevention of NSF and perform a pharmacokinetic-based simulation to determine if the presented evidence is consistent with the established kinetics of GBCAs and Gd.

Adverse Effects of Gadolinium-Based Contrast Agents: Changes in Practice Patterns.

Gadolinium-based contrast agents have been used for magnetic resonance imaging (MRI) examinations since the late 1980s with an excellent overall cumulative safety record. Initially favored for use in patients with renal impairment because of lack of significant nephrotoxic effect at clinical doses, in 2006, multiple reports convincingly linked the rare but serious disease nephrogenic systemic fibrosis to the administration of gadolinium-based contrast agents in patients with severe renal failure. This in turn led to new policies on administration of these agents, resulting in changes in practice patterns that have virtually resulted in the elimination of the disease after the year 2009. The purpose of this review is to summarize the factors that led to the emergence of nephrogenic systemic fibrosis, including the risk associated with different types of contrast agents based on their stability, and the changes in practice patterns and usage of gadolinium-based contrast agents in recent years that have been mainly driven by the discovery and association with nephrogenic systemic fibrosis. The article will conclude with a brief overview of new emerging safety concerns that could further impact the use of this class of contrast agents and impact practice patterns in the future.

Changes in Urinary and Serum Levels of Novel Biomarkers after Administration of Gadolinium-based Contrast Agents.

OBJECTIVEThe aim of our study is to describe the changes in urinary and serum levels of novel biomarkers after gadolinium contrast administration in patients with normal renal function.METHODSWe measured four biomarkers in 28 volunteers: interleukin-18 (IL-18), N-acetyl-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin, and cystatin C. Urinary and serum samples were collected at 0, 3, and 24 hours following gadolinium administration.RESULTSBaseline serum creatinine was 57.8 ± 34.5 µmol/L and remained stable. Urinary IL-18 levels increased significantly at three hours (10.7 vs. 7.3 ng/mg creatinine; P < 0.05). Similarly, urinary NAG levels increased significantly at three hours (3.9 vs. 2.2 IU/mg creatinine; P < 0.001). For both these markers, the difference was no longer significant at 24 hours. No statistically significant differences were observed for urinary and serum neutrophil gelatinase-associated lipocalin levels and for serum cystatin C levels.CONCLUSIONSUrinary IL-18 and NAG levels increased transiently after administration of gadolinium-based contrast agents in patients with normal renal function.

Safe Use of Contrast Media: What the Radiologist Needs to Know

Iodinated and gadolinium-based contrast media are used on a daily basis in most radiology practices. These agents often are essential to providing accurate diagnoses, and are nearly always safe and effective when administered correctly. However, reactions to contrast media do occur and can be life threatening. Therefore, it is critical for faculty and staff to know how reactions to contrast agents manifest and how to treat them promptly. The decline in renal function seen occasionally after intravenous administration of iodinated contrast agents is poorly understood and likely multifactorial, and its association with the contrast medium may be overemphasized. However, it is important that radiologists be aware of current understanding and strategies to decrease the incidence of renal dysfunction. Nephrogenic systemic fibrosis, a skin disease, is an adverse reaction related to use of some gadolinium-based contrast agents in patients with chronic renal failure. The types of gadolinium most often associated with this condition and the indications for withholding gadolinium are important and are discussed in this article. The use of enteric contrast agents and contrast agents during pregnancy and nursing are reviewed briefly. Current knowledge for safe use of contrast media and key concepts that all radiologists should know are summarized in this review.

Dialysability of Gadoteric Acid in Patients With End-Stage Renal Disease Undergoing Hemodialysis

This study was designed to evaluate the dialysability of gadoteric acid in patients with end-stage renal disease (ESRD) requiring hemodialysis. Gadoteric acid is used for magnetic resonance imaging. It is cleared from the blood exclusively by glomerular filtration. In an attempt to decrease the occurrence of nephrogenic systemic fibrosis, hemodialysis has been advocated immediately after injection of gadolinium-based contrast agents in patients with ESRD. Ten patients with ESRD underwent 3 consecutive 4-hour hemodialysis sessions after a single intravenous injection (0.1 mmol/kg) of gadoteric acid. Blood samples were drawn from the vascular access just before and immediately after the end of each 4-hour session. Additional sampling was performed during session 1. Gadoteric acid was efficiently eliminated, with mean (95% confidence interval) clearance values (mL/min) of 224.6 (216.0-233.9) at 0.5 hours and 225.9 (215.6-237.2) at 1.5 hours during session 1. The gadolinium concentration decrease after a 4-hour hemodialysis (vs the corresponding predialysis values) was 97% after session 1. The decrease in gadolinium concentration after session 3 was 99.7% compared with the predialysis concentration of session 1. These percentages are similar to those reported after hemodialysis for other gadolinium-based contrast agents. No adverse effects related to gadoteric acid were reported. Although no unconfounded case of nephrogenic systemic fibrosis has been reported so far after injection of gadoteric acid, hemodialysis can be efficiently used to remove this molecule in patients with ESRD already undergoing long-term hemodialysis.

Emerging applications for ferumoxytol as a contrast agent in MRI.

Ferumoxytol is an ultrasmall superparamagnetic iron oxide (USPIO) agent initially approved by the Food and Drug Administration (FDA) as an iron replacement therapy for patients with anemia due to chronic renal failure. Recently, ferumoxytol has been investigated extensively as an intravenous contrast agent in magnetic resonance imaging (MRI). Since it causes regional T1 and T2 * shortening in vivo, conventional pulse sequences can be used following ferumoxytol administration to demonstrate signal enhancement or loss. Ferumoxytol can be administered as a rapid bolus and has a long intravascular half-life on the order of 14-15 hours, making it a potentially useful agent for vascular and perfusion-weighted MRI. In comparison to other USPIOs, ferumoxytol is less limited by allergic and idiosyncratic reactions. Furthermore, since ferumoxytol is an iron-based agent with no potential for causing nephrogenic systemic fibrosis, it may be useful as an alternative to gadolinium-based contrast agents in patients with compromised renal function. Ferumoxytol is ultimately taken up by macrophages/the reticuloendothelial system in the liver, spleen, and lymph nodes, and this uptake mechanism is being explored as a novel imaging technique for vascular lesions, tumors, and lymph nodes. This article reviews the properties of ferumoxytol relevant to MRI as well as many of the uses for the agent currently under investigation.

Nephrogenic Systemic Fibrosis in a Patient With Renal Failure Demonstrating a “Reverse Superscan” on Bone Scintigraphy

Nephrogenic systemic fibrosis (NSF) has been linked to utilization of gadolinium-based contrast agents in patients with renal impairment. We present a 19-year-old female patient with end-stage renal failure presenting with joint pains and subcutaneous nodules. She had a prior gadolinium-enhanced magnetic resonance angiography when she was 14 years old. Clinical findings revealed firm subcutaneous nodules in both thighs. Whole-body bone scan demonstrates tracer uptake predominantly in the soft tissues and muscles of the extremities with minimal bony uptake. Incisional biopsy of the left thigh nodule revealed features of NSF with a total pathological score of 4, highly consistent with NSF.

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.