A randomized double-blind pilot study to evaluate the efficacy, safety, and tolerability of intravenous iron versus oral iron for the treatment of restless legs syndrome in patients with iron deficiency anemia.

Restless legs syndrome (RLS) is a neurological disorder that can have a profound effect on sleep and quality of life. Idiopathic RLS is associated with brain iron insufficiency despite normal peripheral iron stores. There is, however, a five- to six-fold increase in prevalence of RLS in patients with iron deficiency anemia (IDA). Several open-label trials have demonstrated symptomatic improvement in RLS following treatment of IDA using oral or intravenous iron supplementation. To date, there have been no randomized double-blind controlled trials of intravenous iron compared with oral iron for the treatment of RLS patients with IDA. In the current study, oral ferrous sulfate and ferumoxytol were compared for efficacy and speed of response for treatment of RLS occurring in patients with IDA. The planned recruitment for this study was 70 patients with RLS and IDA, to be randomly assigned 1:1 to oral or intravenous iron, using double-blind, double-dummy procedures. At Week 6, the primary outcomes of Clinical Global Impression-Improvement score and change from baseline in the International Restless Legs Syndrome Study Group rating scale score were assessed. Due to challenges, performing the clinical trial during the COVID-19 pandemic, final-week data were found missing for 30 patients. As a result, in order to maintain the prespecified statistical analysis, an additional 30 patients were recruited. Both IV and oral iron were associated with a marked improvement in RLS symptoms, with no statistically significant difference between treatment groups. No serious adverse events were observed in either treatment group.

IV iron formulations and use in adults.

Intravenous iron has become a major component of the therapeutic armamentarium for iron deficiency and iron deficiency anemia. The earliest formulations were associated with unacceptable toxicity. Newer formulations, with complex carbohydrate cores that bind elemental iron more tightly, allow the administration of full therapeutic doses in 15 to 60 minutes. Nonetheless, a folklore of danger, fueled by earlier formulations no longer available, continues to foment caution. Complement-mediated minor infusion reactions, referred to as complement activation-related pseudo-allergy, resolve without therapy. Inappropriate intervention with vasopressors and H1 blockers converts these minor reactions into hemodynamically significant adverse events. Four new formulations, low-molecular-weight iron dextran, ferumoxytol, ferric carboxymaltose, and ferric derisomaltose, all approved for the treatment of iron deficiency in a host of conditions, are now widely used with an excellent safety profile. Herein, the administration, safety, indications, and management of infusion reactions are discussed. Treatment-emergent hypophosphatemia, a newly recognized side effect for some formulations, is also reviewed. Based on the preponderance of published evidence, intravenous iron should be moved up-front for the treatment of iron deficiency and iron deficiency anemia in those conditions in which oral iron is suboptimal.

Neonatal outcomes from a randomized controlled trial of maternal treatment of iron deficiency anemia with intravenous ferumoxytol vs oral ferrous sulfate.

BACKGROUND: Anemia in pregnancy is common worldwide and has known maternal risks. The relationship between the types of treatment offered for maternal anemia and the effects on the fetus and newborn are largely uninvestigated. OBJECTIVE: This study aimed to investigate whether maternal treatment with intravenous ferumoxytol compared to oral ferrous sulfate results in an increase in neonatal hematologic and iron indices. These analyses were planned secondary outcomes and post hoc analysis from the trial with a primary outcome of change in maternal hemoglobin. STUDY DESIGN: A randomized controlled trial including 124 participants with anemia by World Health Organization criteria was performed in which participants were allocated in a 1:1 ratio to either 2 infusions of 510 mg of intravenous ferumoxytol or 325 mg oral ferrous sulfate twice daily. Fetal monitoring was performed during each intravenous iron infusion. Standard univariable statistical techniques were used to compare groups and to investigate associations between maternal and neonatal hemoglobin and iron indices. RESULTS: Cord blood hematological parameters were equivalent between groups. Hemoglobin was 15.7 g/dL vs 15.4 g/dL (P=.6) and hematocrit was 50.5% and 49.2% (P=.4) in those randomized to intravenous ferumoxytol and oral ferrous sulfate, respectively. Iron studies revealed higher cord blood ferritin concentrations in infants of participants treated with intravenous ferumoxytol (294 vs 186, P=.005). There were equivalent iron (158 vs 146, P=.4), transferrin (186 vs 196, P=.4) and total iron binding capacity (246 vs 244, P=1) in neonates of participants receiving intravenous vs oral treatment. There were no effects of the infusions observed on cardiotocography. Gestational age at birth was equivalent between groups. We noted a larger birthweight in neonates of participants treated with intravenous ferumoxytol (3215 g vs 3033 g, P=.09), which was not statistically significant. Post hoc analyses revealed a statistically significant correlation between neonatal ferritin and maternal hemoglobin (P=.006) and neonatal ferritin and maternal ferritin (P=.017) at admission for delivery. CONCLUSION: Neonates of participants who received intravenous ferumoxytol were born with higher ferritin concentrations in cord blood, at the same gestation with the same birthweight. Participants with higher hemoglobin and ferritin indices delivered infants with higher ferritin concentrations in cord blood.

Ferumoxytol: an emerging therapeutic for iron deficiency anemia.

INTRODUCTION: Iron deficiency anemia (IDA) is common worldwide, and various iron replacement therapies are available. Ferumoxytol is an injectable, high-dose iron formulation (510 mg) that can be administered over a short period (15 min) without test administration. The drug was approved by the Food and Drug Administration in 2009 for the treatment of IDA in patients with chronic kidney disease (CKD), and in 2018, the indication was expanded to include patients without CKD. AREAS COVERED: This paper reviews studies testing the efficacy and safety of ferumoxytol in treating IDA compared with other iron formulations. EXPERT OPINION: There is substantial evidence that ferumoxytol is effective for the treatment of IDA. The efficacy of ferumoxytol in improving anemia is comparable to that of iron sucrose and ferric carboxymaltose (FCM) and superior to that of oral iron or a placebo in replenishing iron stores. Treatment with ferumoxytol, although more expensive, is cost-effective for outpatients requiring parenteral administration because it requires fewer doses and shorter dosing times per dose. Ferumoxytol also causes less frequent hypophosphatemia than FCM. Currently, its use in children and pregnant women is under consideration, which may provide important information for the future applications of ferumoxytol in larger numbers of patients.

In older adults, iron dextran and ferumoxytol each had higher anaphylaxis risk at ≤1 d than iron sucrose.

SOURCE CITATION: Dave CV, Brittenham GM, Carson JL, et al. Risks for anaphylaxis with intravenous iron formulations: a retrospective cohort study. Ann Intern Med. 2022;175:656-64. 35344378.

Association of iron infusion reactions with ABO blood type.

OBJECTIVES: We sought to determine risk factors for iv iron infusion-related reactions (IRR), and identify strategies for iron repletion after IRR. METHODS: We conducted a retrospective chart review of patients treated in the classical hematology clinic at Yale Cancer Center (n = 330 consecutive patients) from 2016 to 2021, who received iv ferumoxytol (60.3%), iron sucrose (14.8%), or iron dextran (10.9%). RESULTS: The iv iron IRR was noted in 58 (17.6%) patients, 62.1% of whom had previously tolerated iv iron. The severity of IRR was mild in 22, moderate in 23, and severe in 11 patients. Most (72.4%) patients who experienced IRR tolerated a subsequent iv iron infusion. On multivariable analysis, a history of non-medication allergies was associated with greater odds of IRR (odds ratio [OR] 2.12, 95% confidence interval (CI): 1.16-3.87, p = .01). No patients with type AB blood, and few with type A blood (n = 6), had IRR; compared to type A or AB together, patients with type B (OR 5.00, 95% CI: 1.56-16.06, p = .007) or type O (OR 3.71, 95% CI: 1.44-9.55, p = .007) blood had greater odds of IRR. CONCLUSIONS: This study highlights a possible association of blood type with iv iron IRR; prospective studies with larger patient numbers are warranted to explore this association.

Analysis of Adverse Events and Intravenous Iron Infusion Formulations in Adults With and Without Prior Infusion Reactions.

Importance: Although iron deficiency is common, it remains unclear which iron repletion strategy is associated with the lowest rate of infusion-related adverse events, and how patients with history of infusion reaction should be managed. Objective: To evaluate rates of infusion reactions among 4 commonly used intravenous iron repletion strategies and determine how readministration was managed in patients with history of reaction. Design, Setting, and Participants: This cohort study included all patients receiving intravenous iron infusion from January 1, 2015, to September 7, 2021, at 6 centers in Portland, Oregon. Participants included a total of 12 237 patients with iron deficiency, not restricted by etiology. Statistical analysis was performed from September to October 2021. Exposures: Type of intravenous iron formulation and concurrent administration of diphenhydramine, epinephrine, famotidine, and/or hydrocortisone, used as surrogate maker of infusion reaction. Main Outcomes and Measures: Incidence of adverse events, including severe events requiring epinephrine, stratified by type of iron formulation, and in patients who received premedication or with history of infusion-related reaction receiving subsequent doses. Results: Among 35 737 unique iron infusions (12 237 patients [9480 (77.5%) women; 717 (5.9%) Black; 10 250 (83.7%) White; mean (SD) age of 51 (20) years]), comprising 22 309 iron sucrose doses, 9067 iron dextran total doses (1771 preceded by test dose, 56 test doses alone), 3147 ferumoxytol doses, and 1214 ferric carboxymaltose doses, incidence of adverse events was 3.9% (n = 1389; 95% CI, 3.7%-4.1%). Rate of infusion events differed among iron formulations: 4.3% (n = 970; 95% CI, 4.1%-4.6%) iron sucrose, 3.8% (n = 345, 95% CI: 3.4%-4.2%) iron dextran (test and full doses or test dose alone), 1.8% (n = 57; 95% CI, 1.4%-2.3%) ferumoxytol, and 1.4% (n = 17, 95% CI, 0.8%-2.3%) ferric carboxymaltose (P < .001). Severe adverse events were exceedingly rare with only 2 documented epinephrine administrations, both associated with iron dextran. Incidence of adverse events among those who received premedication was 23-fold higher compared with those who did not (38.6% vs 1.7%, χ21 = 7324.8; P < .001). Among 873 patients with history of infusion reaction who underwent readministration, the majority received the same formulation, which was associated with significantly higher reaction rate particularly if premedication was administered (68% [95% CI, 64%-72%] vs 32% [95% CI, 26%-41%], respectively), compared with those who received an alternate formulation (21% [95% CI, 11%-35%] vs 5% [95% CI, 2%-12%], respectively) (P < .001). Conclusions and Relevance: These data, and the preponderance of published evidence, suggest that intravenous iron is generally well tolerated with exceedingly low risk of severe reaction, use of premedication and test doses are unnecessary, and that optimal prevention and management of infusion-related reactions warrant further study.

A multicenter study evaluating the effectiveness and safety of single-dose low molecular weight iron dextran vs single-dose ferumoxytol for the treatment of iron deficiency.

There are multiple intravenous (IV) iron formulations available, of which several may be administered as single-dose infusions such as low-molecular weight iron dextran (LMWID), ferumoxytol, ferric carboxymaltose, and ferric derisomaltose. However, administration of ferumoxytol as a single-dose infusion is off-label as it is approved as a two-dose series. Previous studies of ferumoxytol alone support the effectiveness and safety of the single-dose regimen, but there is a paucity of data directly comparing single-dose ferumoxytol to other single-dose IV iron formulations. This multicenter cohort study sought to affirm the safety and effectiveness of single-dose ferumoxytol compared to single-dose LMWID. Overall, 906 patients who received single-dose LMWID (n = 439) or ferumoxytol (n = 467) were identified, of whom 351 met criteria for the primary effectiveness endpoint defined as median change in hemoglobin (Hb), hematocrit (Hct), and ferritin 8 to 12 weeks from baseline. All 906 patients were included for the secondary analysis evaluating the incidence of adverse events (AE) and requirement of additional IV iron infusions. Median change in Hb (LMWID 0.5 g/dL; ferumoxytol 0.8 g/dL; P = .24), Hct (LMWID 1.1%; ferumoxytol 1.25%; P = .89), and ferritin (LMWID 87 ng/dL; ferumoxytol 71 ng/dL; P = .47) was not significantly different between groups. Both groups experienced similar rates of AEs (LMWID 2.3%; ferumoxytol 2.8%; P = .63). The LMWID patients more frequently required additional IV iron infusions (LMWID 28.5%; ferumoxtyol 16.1%; P < .001). These findings support that single-dose ferumoxytol is effective and safe, and that patients may require fewer additional infusions compared to patients who received LMWID.

The safety and efficacy of ferumoxytol in the treatment of iron deficiency: a systematic review and meta-analysis.

INTRODUCTION: Ferumoxytol is an intravenous (IV) iron formulation for treatment of iron deficiency (ID) that faced post-marketing reports of serious adverse events (SAEs). OBJECTIVES: To determine the safety and efficacy of ferumoxytol compared to other iron formulations and placebo. METHODS: We searched the Cochrane Library, Medline, and EMBASE from inception until February 2018 as well as trial registries and reference lists of relevant articles for randomized or quasi-randomized controlled trials. RESULTS: The review included nine studies with 5691 participants. Studies were at low risk of bias. When comparing ferumoxytol to other IV iron formulations, there is moderate quality evidence (QE) of little to no difference in treatment emergent adverse events (TEAEs) (risk ratio [RR] 0.88, 95% confidence interval [CI] 0.80-0.97), treatment related adverse events (TRAEs) (RR 0.73, 95% CI 0.61-0.88), SAEs (RR 1.13, 95% CI 0.77-1.67), hypotension or hypersensitivity reactions (RR 0.58, 95% CI 0.31-1.09), or composite cardiovascular outcomes (RR 0.56, 95% CI 0.24-1.29), low QE of little to no difference in related SAEs (RR 0.55, 95% CI 0.05-6.16), and high QE of little to no difference in the number of patients with an increase in hemoglobin by at least 1 g/dL (RR 1.04, 95% CI 0.96-1.12). Ferumoxytol had less TEAEs compared to oral iron (RR 0.78, 95% CI 0.61-0.98), but more compared to placebo (RR 1.62, 95% CI 1.01-2.61). DISCUSSION: Ferumoxytol is as efficacious and safe as alternative IV iron formulations with no clear safety concerns.

Multicenter Safety and Practice for Off-Label Diagnostic Use of Ferumoxytol in MRI.

Background Ferumoxytol is approved for use in the treatment of iron deficiency anemia, but it can serve as an alternative to gadolinium-based contrast agents. On the basis of postmarketing surveillance data, the Food and Drug Administration issued a black box warning regarding the risks of rare but serious acute hypersensitivity reactions during fast high-dose injection (510 mg iron in 17 seconds) for therapeutic use. Whereas single-center safety data for diagnostic use have been positive, multicenter data are lacking. Purpose To report multicenter safety data for off-label diagnostic ferumoxytol use. Materials and Methods The multicenter ferumoxytol MRI registry was established as an open-label nonrandomized surveillance databank without industry involvement. Each center monitored all ferumoxytol administrations, classified adverse events (AEs) using the National Cancer Institute Common Terminology Criteria for Adverse Events (grade 1-5), and assessed the relationship of AEs to ferumoxytol administration. AEs related to or possibly related to ferumoxytol injection were considered adverse reactions. The core laboratory adjudicated the AEs and classified them with the American College of Radiology (ACR) classification. Analysis of variance was used to compare vital signs. Results Between January 2003 and October 2018, 3215 patients (median age, 58 years; range, 1 day to 96 years; 1897 male patients) received 4240 ferumoxytol injections for MRI. Ferumoxytol dose ranged from 1 to 11 mg per kilogram of body weight (≤510 mg iron; rate ≤45 mg iron/sec). There were no systematic changes in vital signs after ferumoxytol administration (P > .05). No severe, life-threatening, or fatal AEs occurred. Eighty-three (1.9%) of 4240 AEs were related or possibly related to ferumoxytol infusions (75 mild [1.8%], eight moderate [0.2%]). Thirty-one AEs were classified as allergiclike reactions using ACR criteria but were consistent with minor infusion reactions observed with parenteral iron. Conclusion Diagnostic ferumoxytol use was well tolerated, associated with no serious adverse events, and implicated in few adverse reactions. Registry results indicate a positive safety profile for ferumoxytol use in MRI. © RSNA, 2019 Online supplemental material is available for this article.

The Efficacy of Ferumoxytol for Iron Deficiency Anemia: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: This systematic review and meta-analysis aims to explore the influence of ferumoxytol versus placebo on iron deficiency anemia. METHODS: We search for randomized controlled trials (RCTs) assessing the effect of ferumoxytol on iron deficiency anemia on PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases. This meta-analysis is performed using the random-effects model. RESULTS: Four RCTs are included in the meta-analysis. Compared with the control group for iron deficiency anemia, intravenous ferumoxytol can significantly improve the proportion of patients with a ≥20 g/L hemoglobin (Hb) increase (RR = 18.43; 95% CI = 7.29-46.57; p < 0.00001), the proportion of patients with an Hb level ≥120 g/L (RR = 18.55; 95% CI = 8.66-39.72; p < 0.00001), transferrin saturation (mean difference = 11.08; 95% CI = 9.86-12.31; p < 0.00001) and FACIT-fatigue score (mean difference = 4.60; 95% CI = 3.21-6.00; p < 0.00001), but has no remarkable influence on adverse events (RR = 1.33; 95% CI = 0.84-2.10; p = 0.22), serious adverse events (RR = 1.22; 95% CI = 0.74-2.02; p = 0.44), and death (RR = 0.32; 95% CI = 0.05-1.95; p = 0.22). CONCLUSIONS: Intravenous ferumoxytol can provide the important benefits for iron deficiency anemia.

Ferumoxytol for iron deficiency anemia in patients undergoing hemodialysis. The FACT randomized controlled trial
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BACKGROUND: Patients with chronic kidney disease (CKD) undergoing dialysis often require intravenous iron for iron deficiency anemia (IDA). MATERIALS AND METHODS: The Ferumoxytol for Anemia of CKD Trial (FACT), a randomized, multicenter, open-label, phase 4 study, compared the long-term safety and efficacy of ferumoxytol with iron sucrose for the treatment of IDA in patients with CKD undergoing hemodialysis. Patients with IDA and CKD undergoing hemodialysis were randomized 2:1 to ferumoxytol 1.02 g (2 × 510 mg) or iron sucrose 1.0 g (10 × 100 mg) for a 5-week treatment period (TP). Over 11 months, patients underwent additional 5-week TPs whenever IDA (hemoglobin < 11.5 g/dL and transferrin saturation < 30%) was detected. The primary efficacy endpoint was mean change in hemoglobin from baseline to week 5 for each TP. Adverse events were recorded during the study. RESULTS: Overall, 293 patients received ferumoxytol (n = 196) or iron sucrose (n = 97). Ferumoxytol was noninferior to iron sucrose regarding hemoglobin change from baseline to week 5. The mean change in hemoglobin in the ferumoxytol and iron sucrose groups was 0.5 and 0.4 g/dL, respectively, in TP 1 (least-squares mean difference, 0.13; 95% confidence interval, -0.11 to 0.36) and 0.6 and 0.3 g/dL, respectively, in TP 2 (0.30; 0.06 - 0.55). Treatment-related and serious adverse events were similar in both groups; no new safety signals emerged. CONCLUSION: Long-term administration of ferumoxytol has noninferior efficacy and a similar safety profile to iron sucrose when used to treat IDA in patients with CKD undergoing hemodialysis.
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Ferumoxytol for the treatment of iron deficiency anemia.

INTRODUCTION: Ferumoxytol is a superparamagnetic molecule originally developed as a contrast agent for magnetic resonance imaging. Elemental iron is contained within the carbohydrate core and is released slowly after infusion allowing a large dose of iron to be administered in a short period of time. Ferumoxytol, originally approved for iron deficiency in chronic kidney disease, received a broad label for any cause of iron deficiency after oral iron intolerance or in those circumstances when oral iron is ineffective or harmful. Areas covered: The chemistry, pharmacology and pharmacokinetics of ferumoxytol were reviewed. Retrospective, observational, and prospective phase II and III trials were reviewed. When appropriate, comparative safety and efficacy parameters were reported. Differentiation between minor infusion reactions and more severe hypersensitivity reactions that may lead to anaphylaxis is described. Expert commentary: Ferumoxytol is a safe and effective iron formulation providing a means of iron repletion in persons with iron deficiency with or without anemia. Relative to iron sucrose, ferric gluconate, and iron dextran and similar to ferric carboxymaltose and iron isomaltoside, ferumoxytol yields relatively low quantities of labile free iron. Hypersensitivity and anaphylaxis is extremely rare. Hypophosphatemia with ferumoxytol's administration is extremely rare. Optimal strategies for application of ferumoxytol-enhanced imaging and full replacement dosing in a single setting remain to be determined.

Adverse Reactions After Intravenous Iron Infusion Among Inflammatory Bowel Disease Patients in the United States, 2010-2014.

Background: Anemia is a frequent complication of Crohn's disease (CD) and ulcerative colitis (UC), collectively known as inflammatory bowel disease (IBD). Intravenous (IV) iron is recommended as the initial therapy for patients with clinically active IBD, severe anemia, and intolerance to oral iron. IV iron is associated with serious adverse effects including a black box warning for anaphylaxis with iron dextran and ferumoxytol. We aimed to examine the occurrence of adverse reactions including anaphylaxis after IV iron infusions in a large database of US IBD patients. Methods: We performed a retrospective analysis for encounters occurring between 2010 and 2014 in MarketScan, a US commercial claims database. We assessed the following adverse events: anaphylactic shock, bronchospasm, and hypotension among IBD patients receiving ferumoxytol, iron dextran, ferric gluconate, iron sucrose, and ferric carboxymaltose. We calculated the adverse event rate per 1000 infusions within 7 days of IV iron infusion. Results: In our study cohort of 6151 IBD patients (38.4% UC), 37 168 IV iron infusions were given (median, 3 infusions). There were very few adverse events; only 1.3% of IBD patients experienced any adverse reaction. The incident rate per 1000 infusions for any adverse event among IBD patients was highest among those receiving ferumoxytol (2.54, 95% confidence interval [CI], 1.26-5.11), ferric gluconate (1.85; 95% CI, 1.03-3.35), iron sucrose (1.74; 95% CI, 1.09-2.78), and iron dextran (0.96; 95% CI, 0.43-2.13). There were 0.24 anaphylactic shock events per 1000 IV iron infusions. Conclusions: About 1.3 of 100 IBD patients ever developed any adverse event. Because adverse reactions are rare, physicians should be encouraged to adhere to recommended guidelines for iron replacement among anemic IBD patients. 10.1093/ibd/izy063_video1izy063.video15768853346001.

Comparative safety of intravenous ferumoxytol versus ferric carboxymaltose in iron deficiency anemia: A randomized trial.

Few trials have examined rates of hypersensitivity reactions (HSRs) with intravenous iron formulations used to treat iron deficiency anemia (IDA). This randomized, multicenter, double-blind clinical trial compared the safety, and efficacy of ferumoxytol versus ferric carboxymaltose (FCM), focusing on rates of HSRs and hypotension as the primary end point. Patients with IDA of any etiology in whom oral iron was unsatisfactory or intolerable received ferumoxytol (n = 997) or FCM (n = 1000) intravenously over ≥15 minutes on days 1 and 8 or 9 for total respective doses of 1.02 g and 1.50 g. Composite incidences of moderate-to-severe HSRs, including anaphylaxis, or moderate-to-severe hypotension from baseline to week 5 (primary safety end point) were 0.6% and 0.7% in the ferumoxytol and FCM groups, respectively, with ferumoxytol noninferior to FCM. No anaphylaxis was reported in either group. The secondary safety end point of incidences of moderate-to-severe HSRs, including anaphylaxis, serious cardiovascular events, and death from baseline to week 5 were 1.3% and 2.0% in the ferumoxytol and FCM groups, respectively (noninferiority test P < .0001). Least-squares mean changes in hemoglobin at week 5 were 1.4 g/dL and 1.6 g/dL in the ferumoxytol and FCM groups, respectively (noninferiority test P < .0001). Incidence of hypophosphatemia was 0.4% for ferumoxytol and 38.7% for FCM.

Novel contrast mixture achieves contrast resolution of human bladder wall suitable for T1 mapping: applications in interstitial cystitis and beyond.

PURPOSE: Instillation of novel contrast mixture (NCM) was recently shown to improve the contrast resolution of rat bladder wall with high contrast-to-noise ratio (CNR). Here, the clinical safety and the feasibility of NCM-enhanced MRI to achieve artifact-free visualization of human bladder wall suitable for quantitative measurement of the magnetic resonance (MR) longitudinal relaxation time (T1) was assessed. METHODS: Six female subjects [two controls and two with Hunner-type interstitial cystitis IC and two with non-Hunner-type IC] consented for MRI at 3 T before and after instillation of NCM [4 mM gadobutrol and 5 mM ferumoxytol in 50 mL of sterile water for injection]. Single breath-hold fast MR acquisition in large readout bandwidth for 5-mm-thick single slice with variable flip angle was applied to minimize the motion and chemical shift artifacts in measurements of bladder wall thickness (BWT), CNR and T1 from 20 pixels. RESULTS: NCM instillation in subjects did not evoke pain or discomfort. Fourfold increase in bladder wall CNR (*p < 0.02) and pixel size of 0.35 mm with minimal influence of artifacts allowed accurate determination of bladder wall thinning ~ 0.46 mm from 50 mL NCM (*p < 0.05). Pre-contrast bladder wall T1 of 1544 ± 34.2 ms was shortened to 860.09 ± 13.95 ms in Hunner-type IC (*p < 0.0001) relative to only 1257.42 ± 20.59 and 1258.16 ± 6.16 ms in non-Hunner-type IC and controls, respectively. CONCLUSION: Findings demonstrate the safety and feasibility of NCM-enhanced MRI to achieve artifact-free differential contrast and spatial resolution of human bladder wall, which is suitable for measuring BWT and pixel-wise measurement of T1 in post-contrast setting.

4D flow image quality with blood pool contrast: a comparison of gadofosveset trisodium and ferumoxytol.

To evaluate the effect of MRI blood pool contrast agent on 4D flow image quality and ventricular volume measurements. Adult patients referred for clinical cardiac MRI (n = 22) were imaged with 4D flow. Patients with renal failure (n = 10) received ferumoxytol, and the remainder (n = 12) received gadofosveset trisodium. Image quality was assessed with (1) signal-to-noise ratio (SNR); (2) contrast-to-noise ratio (CNR); and (3) 5-point Likert scale based on endocardial border definition (1 = none; 2 = partial but unable to visualize; 3 = able to roughly estimate; 4 = visible for most of the cardiac cycle; 5 = excellent definition). A subset (n = 15) had short axis steady-state free precession (SSFP) cine imaging allowing for comparison of standard volumetric measurement technique with 4D flow derived volumetric measurements. 4D flow studies using ferumoxytol demonstrated a higher median Likert score of 5 (IQR, 5-5) versus 3 (IQR, 2-3). Median cavity SNR and CNR were higher for ferumoxytol compared to gadofosveset trisodium [65 (IQR, 50-74) versus 22 (IQR, 14-28), p < 0.001; and 40 (IQR, 32-49) versus 4 (IQR, 3-10), p < 0.001]. Good correlation (p < 0.001) was seen between SSFP and 4D flow measured ventricular volumes (ESV and EDV) with ferumoxytol (r = 0.998, mean difference = 1.2 mL, LOA = - 7.7-10.1 mL) and gadofosveset trisodium (r = 0.942, mean difference = - 2.7 mL, LOA = - 35.7-27.1 mL). Ferumoxytol used off-label as an MRI blood pool contrast agent offers an attractive alternative to gadofosveset trisodium in patients with renal failure, with excellent 4D flow image quality and good correlation of volumetric measurements compared to the CMR reference (SSFP).