Hemodynamic Assessment of Infants With Congenital Heart Disease Using Ferumoxytol-Enhanced 4D Flow Cardiac Magnetic Resonance.

In complex congenital heart disease, characterization of the circulation is necessary to anticipate the clinical course. Four-dimensional cardiac magnetic resonance imaging enhanced by superparamagnetic iron oxide contrast agents (ferumoxytol) enables detailed and efficient assessment of both anatomy and physiology in neonates. We demonstrate this impact in 3 cases of neonates with congenital heart disease.

Enhancement of the lymphatic system following intravenous administration of ferumoxytol.

BACKGROUND: Lymphatic imaging is becoming increasingly important in the management of patients with congenital heart disease. However, the influence of the intravenous contrast agent ferumoxytol on lymphatic imaging is not well understood. OBJECTIVE: To evaluate the impact of intravenous ferumoxytol on T1-weighted and T2-weighted lymphatic imaging in patients with congenital heart disease. MATERIALS AND METHODS: We included consecutive patients receiving ferumoxytol-enhanced 3D angiography for congenital heart disease evaluation. The visibility of the thoracic duct was reviewed on the T1-weighted 3D inversion recovery balanced-steady-state free precession (SSFP) with respiratory navigator gating sequence which is routinely used for angiography and the heavily T2-weighted turbo spin echo sequence which is employed for lymphatic imaging. Data on demographics and time interval between contrast administration and imaging were collected. Statistical analyses were performed using t-tests for continuous variables and chi-squared tests for categorical variables. RESULTS: One hundred nineteen consecutive patients with a mean age of 12.46 years±7.7 years were included. Of these, 45 cases underwent both T1-weighted and T2-weighted imaging; the other 74 underwent only T1-weighted imaging. Of the 45 patients, 20 had thoracic duct enhancement on T1-weighted imaging; among the 26 sedated, only 2 showed enhancement, while 18 of 19 non-sedated patients showed enhancement (P<0.001), indicating a strong association between sedation and reduced thoracic duct visibility. If T2-weighted imaging was performed after contrast administration, the thoracic duct was not visible on those images. For all 45 cases of visible thoracic duct in the entire cohort, the time from contrast administration to imaging ranged from 8 min up to 75 min. CONCLUSION: The enhancement of the thoracic lymphatic duct on T1-weighted imaging, coupled with degradation observed on T2-weighted imaging, suggests that intravenously administered ferumoxytol rapidly enters the lymphatic fluid. To prevent T2 shortening from degrading the imaging results, T2-weighted imaging for lymphatic evaluation should be performed prior to the administration of ferumoxytol. Sedation and, by inference, fasting may influence this property and warrant further investigation in future studies.

Delayed Ferumoxtran-10-Enhanced Magnetic Resonance Neurography of the Lumbosacral Plexus: Impact on Vascular Suppression and Image Quality.

BACKGROUND: Intravenous Ferumoxtran-10 belongs to ultra-small superparamagnetic iron oxide particles and can be used for magnetic resonance neurography (MRN) as an alternative to other imaging methods which use contrast agents. PURPOSE: To examine the impact of intravenous Ferumoxtran-10 on vascular suppression and compare image quality to gadolinium (Gd)-enhanced image acquisition in MRN of lumbosacral plexus (LS). STUDY TYPE: Prospective. POPULATION/SUBJECTS: 17 patients with Ferumoxtran-10-enhanced MRN, and 20 patients with Gd-enhanced MRN. FIELDSTRENGTH/SEQUENCE: 3T/3D STIR sequence. ASSESSMENT: Image quality, nerve visibility and vascular suppression were evaluated by 3 readers using a 5-point Likert scale. STATISTICAL TESTS: Inter-reader agreement (IRA) was calculated using intraclass coefficients (ICC). Quantitative analysis of image quality was performed by signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) measurements and compared using Student's t-testing. RESULTS: Image quality, nerve visibility and vascular suppression were significantly higher for Ferumoxtran-10-enhanced MRN compared to Gd-enhanced MRN sequences (p < 0.05). IRA for image quality of nerves was good in Gd-enhanced and Ferumoxtran-10 MRN with ICC values of 0.76 and 0.89, respectively. IRA for nerve visibility was good in Gd- and Ferumoxtran-10 enhanced MR neurography (ICC 0.72 and 0.90). Mean SNR was significantly higher in Ferumoxtran-10-enhanced MRN for all analyzed structures, while mean CNR was for significantly better for S1 ganglion and femoral nerve in Ferumoxtran-10-enhanced MRN (p < 0.05). DATA CONCLUSION: Ferumoxtran-10-enhanced MRN of the LS plexus showed significantly higher image quality and nerve visibility with better vascular suppression as compared to Gd-enhanced MRN. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Ferumoxytol-Enhanced 5D Multiphase Steady-State Imaging Using Rotating Cartesian K-Space With Low-Rank Reconstruction for Pediatric Congenital Heart Disease.

BACKGROUND: The rotating Cartesian k-space multiphase steady-state imaging with contrast (ROCK-MUSIC) pulse sequence enables acquisition of whole-heart, cardiac phase-resolved images in pediatric congenital heart disease (CHD) without reliance on the ventilator gating signal. Multidimensional reconstruction with low rank tensor (LRT) has shown promise for resolving complex cardiorespiratory motion. PURPOSE: To enhance ROCK-MUSIC by resolving cardiorespiratory phases using LRT reconstruction and to enable semi-automatic hyperparameter tuning by developing an image quality scoring model. STUDY TYPE: Retrospective. POPULATION: Thirty patients (45% female, age 2 days to 6.7 years) with CHD. FIELD STRENGTH/SEQUENCE: 3-T, four-dimensional (4D) spoiled gradient recalled echo sequence. ASSESSMENT: Eigenvector-based iTerative Self-consistent Parallel Imaging Reconstruction (ESPIRiT) served as the reference comparison for LRT reconstruction. A 4-point Likert scale was used for cardiac and vascular image quality scoring based on cardiac chamber definition, lumen signal uniformity, vascular margin clarity, and motion artifact. Ejection fraction and ventricular volumes were assessed in 16 patients. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and edge sharpness were computed. STATISTICAL TESTS: Intraclass correlation coefficients, Wilcoxon signed-rank test, Bland-Altman. A P-value <0.05 was considered statistically significant. RESULTS: Relative to ESPIRiT, LRT images received significantly higher cardiac (2.81 ± 0.57 vs. 3.19 ± 0.54) and vascular (2.81 ± 0.60 vs. 3.36 ± 0.53) image quality scores. Image quality scoring with semi-automated hyperparameter tuning showed strong correlations (R2 = 0.748) among image quality, SNR, and septal sharpness. Comparison of ejection fraction and volumetry derived from ESPIRiT, and LRT showed no significant systematic difference (P = 0.32). DATA CONCLUSION: Integration of low-rank reconstruction with ROCK-MUSIC acquisition may be feasible, and semi-automatic hyperparameter tuning could be effective for generating cardiorespiratory resolved images. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

A case of severe anaphylactic reaction after administration of diagnostic-dose ferumoxytol in a pediatric patient.

We describe a case of anaphylaxis during administration of intravenous (IV) ferumoxytol as a magnetic resonance imaging (MRI) contrast agent in a 4-year-old patient with complicated past medical history including YARS genetic mutation with resultant liver failure and deceased donor liver transplantation, stage IV chronic kidney disease (CKD), and hypertension. The patient was noted to have labored breathing 4 min after initiation of ferumoxytol infusion and was subsequently rapidly intubated and returned to the intensive care unit (ICU) for monitoring. Anaphylactic reactions to therapeutic doses of ferumoxytol led to issuance of a black box warning by the FDA in 2015. Adverse reactions to lower-dose ferumoxytol used in diagnostic imaging, however, are rare and there has been a paucity of documented anaphylactic reactions in the literature.

Ferumoxytol-enhanced MRI assessment of venous Thrombus resolution and macrophage content in a murine deep vein thrombosis model.

BACKGROUND: Imaging evaluation of acute deep vein thrombosis (DVT) or post-thrombotic syndrome (PTS) in animal or clinical models is limited to anatomical assessment of the location and extent of thrombi. We hypothesize that Fe-MRI, used to evaluate macrophage content in other inflammatory diseases, can be useful to evaluate the thromboinflammatory features after DVT over time. METHODS: Nineteen wild-type CD-1 mice underwent surgical IVC ligation to induce DVT. Mice received either saline or 5 mg/kg of 14E11, a Factor XI inhibitor, before the procedure. Fe-MRI was performed on days 6-7 after ligation to evaluate thrombus volume, perfusion, and macrophage content via T2-weighted images. Mice were euthanized at days 3-15 after surgery. The thrombi and adjacent vein walls were excised, weighed, formalin-fixed, and paraffin-embedded for immunohistological analysis. Specimens were stained with specific antibodies to evaluate macrophage content, collagen deposition, neovascularization, and recanalization. Significance was determined using the Mann-Whitney U or Student's t-test. RESULTS: After IVC-ligation in control mice, thrombus weights decreased by 59 % from day 3 to 15. Thrombus volumes peaked on day 5 before decreasing by 85 % by day 13. FXI inhibition led to reduced macrophage content in both thrombi (p = .008) and vein walls (p = .01), decreased thrombus volume (p = .03), and decreased thrombus mass (p = .01) compared to control mice. CCR2+ staining corroborated these findings, showing significantly reduced macrophage presence in the thrombi (p = .002) and vein wall (p = .002). CONCLUSIONS: Fe-MRI T2 relaxation times can be used to characterize and quantify post-thrombotic changes of perfusion, macrophage content, and thrombus volume over time in a surgical mouse model of venous thrombosis. This approach could lead to better quantification of in vivo inflammation correlating monocyte and macrophage content within resolving thrombi and veins and may serve as a useful tool for research and clinically in the evaluation of the post-thrombotic environment.

Mapping vascular network architecture in primate brain using ferumoxytol-weighted laminar MRI.

Mapping the vascular organization of the brain is of great importance across various domains of basic neuroimaging research, diagnostic radiology, and neurology. However, the intricate task of precisely mapping vasculature across brain regions and cortical layers presents formidable challenges, resulting in a limited understanding of neurometabolic factors influencing the brain's microvasculature. Addressing this gap, our study investigates whole-brain vascular volume using ferumoxytol-weighted laminar-resolution multi-echo gradient-echo imaging in macaque monkeys. We validate the results with published data for vascular densities and compare them with cytoarchitecture, neuron and synaptic densities. The ferumoxytol-induced change in transverse relaxation rate (ΔR2*), an indirect proxy measure of cerebral blood volume (CBV), was mapped onto twelve equivolumetric laminar cortical surfaces. Our findings reveal that CBV varies 3-fold across the brain, with the highest vascular volume observed in the inferior colliculus and lowest in the corpus callosum. In the cerebral cortex, CBV is notably high in early primary sensory areas and low in association areas responsible for higher cognitive functions. Classification of CBV into distinct groups unveils extensive replication of translaminar vascular network motifs, suggesting distinct computational energy supply requirements in areas with varying cytoarchitecture types. Regionally, baseline R2* and CBV exhibit positive correlations with neuron density and negative correlations with receptor densities. Adjusting image resolution based on the critical sampling frequency of penetrating cortical vessels, allows us to delineate approximately 30% of the arterial-venous vessels. Collectively, these results mark significant methodological and conceptual advancements, contributing to the refinement of cerebrovascular MRI. Furthermore, our study establishes a linkage between neurometabolic factors and the vascular network architecture in the primate brain.

The use of ferumoxytol for high-resolution vascular imaging and troubleshooting for abdominal allografts.

Ferumoxytol is an ultrasmall superparamagnetic iron oxide which has been used as an off-label intravenous contrast agent for MRI. Unlike gadolinium-based contrast agents, ferumoxytol remains in the intravascular space with a long half-life of 14-21 h. During the first several hours, it acts as a blood-pool agent and has minimal parenchymal enhancement. Studies have shown adequate intravascular signal for up to 72 h after initial contrast bolus. Ferumoxytol has been shown to be safe, even in patients with renal failure. Ferumoxytol has shown promise in a variety of clinical settings. The exquisite resolution enabled by the long intravascular times and lack of background parenchymal enhancement is of particular interest in the vascular imaging of solid organ allografts. Ferumoxytol magnetic resonance angiography (MRA) may identify clinically actionable findings months before ultrasound, CT angiography, or Gadolinium-enhanced MRA. Ferumoxytol MRA is of particular benefit as a troubleshooting tool in the setting of equivocal ultrasound and CT imaging. In the following review, we highlight the use of ferumoxytol for high-resolution MR vascular imaging for abdominal solid organ allografts, with representative cases.

Unveiling the next generation of MRI contrast agents: current insights and perspectives on ferumoxytol-enhanced MRI.

Contrast-enhanced magnetic resonance imaging (CE-MRI) is a pivotal tool for global disease diagnosis and management. Since its clinical availability in 2009, the off-label use of ferumoxytol for ferumoxytol-enhanced MRI (FE-MRI) has significantly reshaped CE-MRI practices. Unlike MRI that is enhanced by gadolinium-based contrast agents, FE-MRI offers advantages such as reduced contrast agent dosage, extended imaging windows, no nephrotoxicity, higher MRI time efficiency and the capability for molecular imaging. As a leading superparamagnetic iron oxide contrast agent, ferumoxytol is heralded as the next generation of contrast agents. This review delineates the pivotal clinical applications and inherent technical superiority of FE-MRI, providing an avant-garde medical-engineering interdisciplinary lens, thus bridging the gap between clinical demands and engineering innovations. Concurrently, we spotlight the emerging imaging themes and new technical breakthroughs. Lastly, we share our own insights on the potential trajectory of FE-MRI, shedding light on its future within the medical imaging realm.

Comparison of dynamic susceptibility contrast (DSC) using gadolinium and iron-based contrast agents in high-grade glioma at high-field MRI.

PURPOSE: To compare DSC-MRI using Gadolinium (GBCA) and Ferumoxytol (FBCA) in high-grade glioma at 3T and 7T MRI field strengths. We hypothesized that using FBCA at 7T would enhance the performance of DSC, as measured by contrast-to-noise ratio (CNR). METHODS: Ten patients (13 lesions) were assigned to 3T (6 patients, 6 lesions) or 7T (4 patients, 7 lesions). All lesions received 0.1 mmol/kg of GBCA on day 1. Ten lesions (4 at 3T and 6 at 7T) received a lower dose (0.6 mg/kg) of FBCA, followed by a higher dose (1.0-1.2 mg/kg), while 3 lesions (2 at 3T and 1 at 7T) received only a higher dose on Day 2. CBV maps with leakage correction for GBCA but not for FBCA were generated. The CNR and normalized CBV (nCBV) were analyzed on enhancing and non-enhancing high T2W lesions. RESULTS: Regardless of FBCA dose, GBCA showed higher CNR than FBCA at 7T, which was significant for high-dose FBCA (p < .05). Comparable CNR between GBCA and high-dose FBCA was observed at 3T. There was a trend toward higher CNR for FBCA at 3T than 7T. GBCA also showed nCBV twice that of FBCA at both MRI field strengths with significance at 7T. CONCLUSION: GBCA demonstrated higher image conspicuity, as measured by CNR, than FBCA on 7T. The stronger T2* weighting realized with higher magnetic field strength, combined with FBCA, likely results in more signal loss rather than enhanced performance on DSC. However, at clinical 3T, both GBCA and FBCA, particularly a dosage of 1.0-1.2 mg/kg (optimal for perfusion imaging), yielded comparable CNR.

Ferumoxytol-Enhanced Cardiac Cine MRI Reconstruction Using a Variable-Splitting Spatiotemporal Network.

BACKGROUND: Balanced steady-state free precession (bSSFP) imaging is commonly used in cardiac cine MRI but prone to image artifacts. Ferumoxytol-enhanced (FE) gradient echo (GRE) has been proposed as an alternative. Utilizing the abundance of bSSFP images to develop a computationally efficient network that is applicable to FE GRE cine would benefit future network development. PURPOSE: To develop a variable-splitting spatiotemporal network (VSNet) for image reconstruction, trained on bSSFP cine images and applicable to FE GRE cine images. STUDY TYPE: Retrospective and prospective. SUBJECTS: 41 patients (26 female, 53 ± 19 y/o) for network training, 31 patients (19 female, 49 ± 17 y/o) and 5 healthy subjects (5 female, 30 ± 7 y/o) for testing. FIELD STRENGTH/SEQUENCE: 1.5T and 3T, bSSFP and GRE. ASSESSMENT: VSNet was compared to VSNet with total variation loss, compressed sensing and low rank methods for 14× accelerated data. The GRAPPA×2/×3 images served as the reference. Peak signal-to-noise-ratio (PSNR), structural similarity index (SSIM), left ventricular (LV) and right ventricular (RV) end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) were measured. Qualitative image ranking and scoring were independently performed by three readers. Latent scores were calculated based on scores of each method relative to the reference. STATISTICS: Linear mixed-effects regression, Tukey method, Fleiss' Kappa, Bland-Altman analysis, and Bayesian categorical cumulative probit model. A P-value <0.05 was considered statistically significant. RESULTS: VSNet achieved significantly higher PSNR (32.7 ± 0.2), SSIM (0.880 ± 0.004), rank (2.14 ± 0.06), and latent scores (-1.72 ± 0.22) compared to other methods (rank >2.90, latent score < -2.63). Fleiss' Kappa was 0.52 for scoring and 0.61 for ranking. VSNet showed no significantly different LV and RV ESV (P = 0.938) and EF (P = 0.143) measurements, but statistically significant different (2.62 mL) EDV measurements compared to the reference. CONCLUSION: VSNet produced the highest image quality and the most accurate functional measurements for FE GRE cine images among the tested 14× accelerated reconstruction methods. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

Manifold-based denoising for Ferumoxytol-enhanced 3D cardiac cine MRI.

The two-dimensional (2D) cine cardiovascular magnetic resonance (CMR) technique is the reference standard for assessing cardiac function. However, one challenge with 2D cine is that the acquisition time for the whole cine stack is long and requires multiple breath holds, which may not be feasible for pediatric or ill patients. Though single breath-hold multi-slice cine may address the issue, it can only acquire low-resolution images, and hence, affect the accuracy of cardiac function assessment. To address these challenges, a Ferumoxytol-enhanced, free breathing, isotropic high-resolution 3D cine technique was developed. The method produces high-contrast cine images with short acquisition times by using compressed sensing together with a manifold-based method for image denoising. This study included fifteen patients (9.1 $ \pm $ 5.6 yrs.) who were referred for clinical cardiovascular magnetic resonance imaging (MRI) with Ferumoxytol contrast and were prescribed the 3D cine sequence. The data was acquired on a 1.5T scanner. Statistical analysis shows that the manifold-based denoised 3D cine can accurately measure ventricular function with no significant differences when compared to the conventional 2D breath-hold (BH) cine. The multiplanar reconstructed images of the proposed 3D cine method are visually comparable to the golden standard 2D BH cine method in terms of clarity, contrast, and anatomical precision. The proposed method eliminated the need for breath holds, reduced scan times, enabled multiplanar reconstruction within an isotropic data set, and has the potential to be used as an effective tool to access cardiovascular conditions.

Cotyledon-Specific Flow Evaluation of Rhesus Macaque Placental Injury Using Ferumoxytol Dynamic Contrast-Enhanced MRI.

BACKGROUND: Recently, dynamic contrast-enhanced (DCE) MRI with ferumoxytol as contrast agent has recently been introduced for the noninvasive assessment of placental structure and function throughout. However, it has not been demonstrated under pathological conditions. PURPOSE: To measure cotyledon-specific rhesus macaque maternal placental blood flow using ferumoxytol DCE MRI in a novel animal model for local placental injury. STUDY TYPE: Prospective animal model. SUBJECTS: Placental injections of Tisseel (three with 0.5 mL and two with 1.5 mL), monocyte chemoattractant protein 1 (three with 100 µg), and three with saline as controls were performed in a total of 11 rhesus macaque pregnancies at approximate gestational day (GD 101). DCE MRI scans were performed prior (GD 100) and after (GD 115 and GD 145) the injection (term = GD 165). FIELD STRENGTH/SEQUENCE: 3 T, T1-weighted spoiled gradient echo sequence (product sequence, DISCO). ASSESSMENT: Source images were inspected for motion artefacts from the mother or fetus. Placenta segmentation and DCE processing were performed for the dynamic image series to measure cotyledon specific volume, flow, and normalized flow. Overall placental histopathology was conducted for controls, Tisseel, and MCP-1 animals and regions of tissue infarctions and necrosis were documented. Visual inspections for potential necrotic tissue were conducted for the two Tisseelx3 animals. STATISTICAL TESTS: Wilcoxon rank sum test, significance level P < 0.05. RESULTS: No motion artefacts were observed. For the group treated with 1.5 mL of Tisseel, significantly lower cotyledon volume, flow, and normalized flow per cotyledon were observed for the third gestational time point of imaging (day ~145), with mean normalized flow of 0.53 minute-1. Preliminary histopathological analysis shows areas of tissue necrosis from a selected cotyledon in one Tisseel-treated (single dose) animal and both Tisseelx3 (triple dose) animals. DATA CONCLUSION: This study demonstrates the feasibility of cotyledon-specific functional analysis at multiple gestational time points and injury detection in a placental rhesus macaque model through ferumoxytol-enhanced DCE MRI. LEVEL OF EVIDENCE: NA TECHNICAL EFFICACY: Stage 2.

MRI Detection and Therapeutic Enhancement of Ferumoxytol Internalization in Glioblastoma Cells.

Recently, the FDA-approved iron oxide nanoparticle, ferumoxytol, has been found to enhance the efficacy of pharmacological ascorbate (AscH-) in treating glioblastoma, as AscH- reduces the Fe3+ sites in the nanoparticle core. Given the iron oxidation state specificity of T2* relaxation mapping, this study aims to investigate the ability of T2* relaxation to monitor the reduction of ferumoxytol by AscH- with respect to its in vitro therapeutic enhancement. This study employed an in vitro glioblastoma MRI model system to investigate the chemical interaction of ferumoxytol with T2* mapping. Lipofectamine was utilized to facilitate ferumoxytol internalization and assess intracellular versus extracellular chemistry. In vitro T2* mapping successfully detected an AscH--mediated reduction of ferumoxytol (25.6 ms versus 2.8 ms for FMX alone). The T2* relaxation technique identified the release of Fe2+ from ferumoxytol by AscH- in glioblastoma cells. However, the high iron content of ferumoxytol limited T2* ability to differentiate between the external and internal reduction of ferumoxytol by AscH- (ΔT2* = +839% for external FMX and +1112% for internal FMX reduction). Notably, the internalization of ferumoxytol significantly enhances its ability to promote AscH- toxicity (dose enhancement ratio for extracellular FMX = 1.16 versus 1.54 for intracellular FMX). These data provide valuable insights into the MR-based nanotheranostic application of ferumoxytol and AscH- therapy for glioblastoma management. Future developmental efforts, such as FMX surface modifications, may be warranted to enhance this approach further.

The Story of Ferumoxytol: Synthesis Production, Current Clinical Applications, and Therapeutic Potential.

Ferumoxytol, approved by the U.S. Food and Drug Administration in 2009, is one of the intravenous iron oxide nanoparticles authorized for the treatment of iron deficiency in chronic kidney disease and end-stage renal disease. With its exceptional magnetic properties, catalytic activity, and immune activity, as well as good biocompatibility and safety, ferumoxytol has gained significant recognition in various biomedical diagnoses and treatments. Unlike most existing reviews on this topic, this review primarily focuses on the recent clinical and preclinical advances of ferumoxytol in disease treatment, spanning anemia, cancer, infectious inflammatory diseases, regenerative medicine application, magnetic stimulation for neural modulation, etc. Additionally, the newly discovered mechanisms associated with the biological effects of ferumoxytol are discussed, including its magnetic, catalytic, and immunomodulatory properties. Finally, the summary and future prospects concerning the treatment and application of ferumoxytol-based nanotherapeutics are presented.

Cardiothoracic Magnetic Resonance Angiography.

Catheter-based angiography is regarded as the clinical reference imaging technique for vessel imaging; however, it is invasive and is currently used for intervention or physiologic measurements. Contrast enhanced magnetic resonance angiography (MRA) with gadolinium-based contrast agents can be performed as a three-dimensional (3D) MRA or as a time resolved 3D (4D) MRA without physiologic synchronization, in which case cardiac and respiratory motion may blur the edges of the vessels and cardiac chambers. Ferumoxytol has recently been a popular contrast agent for MRA in patients with chronic renal failure. Noncontrast 3D MRA with ECG gating and respiratory navigation are safe and accurate noninvasive cross-sectional imaging techniques for the visualization of great vessels of the heart and coronary arteries in a variety of cardiovascular disorders including complex congenital heart diseases. Noncontrast flow dependent MRA techniques such as time of flight, phase contrast, and black-blood MRA techniques can be used as complementary or primary techniques. Here we review both conventional and relatively new contrast enhanced and non-contrast enhanced MRA techniques including ferumoxytol enhanced MRA, and bright-blood and water-fat separation based noncontrast 3D MRA techniques.

Deciphering spatially distinct immune microenvironments in glioblastoma using ferumoxytol and gadolinium-enhanced and FLAIR hyperintense MRI phenotypes.

Background: MRI with gadolinium (Gd)-contrast agents is used to assess glioblastoma treatment response but does not specifically reveal heterogeneous biology or immune microenvironmental composition. Ferumoxytol (Fe) contrast is an iron nanoparticle that localizes glioblastoma macrophages and microglia. Therefore, we hypothesized that the use of Fe contrast improves upon standard Gd-based T1-weighted and T2/FLAIR analysis by specifically delineating immune processes. Methods: In this, HIPAA-compliant institutional review board-approved prospective study, stereotactic biopsy samples were acquired from patients with treatment-naïve and recurrent glioblastoma based on MR imaging phenotypes; Gd and Fe T1 enhancement (Gd+, Fe+) or not (Gd-, Fe-), as well as T2-Flair hyperintensity (FLAIR+, FLAIR-). Analysis of genetic expression was performed with RNA microarrays. Imaging and genomic expression patterns were compared using false discovery rate statistics. Results: MR imaging phenotypes defined a variety of immune pathways and Hallmark gene sets. Gene set enrichment analysis demonstrated that Gd+, Fe+, and FLAIR+ features were individually correlated with the same 7 immune process gene sets. Fe+ tissue showed the greatest degree of immune Hallmark gene sets compared to Gd+ or Flair+ tissues and had statistically elevated M2 polarized macrophages, among others. Importantly, the FLAIR+ Gd+ and Fe- imaging phenotypes did not demonstrate expression of immune Hallmark gene sets. Conclusions: Our study demonstrates the potential of Fe and Gd-enhanced MRI phenotypes to reveal spatially distinct immune processes within glioblastoma. Fe improves upon the standard of care Gd enhancement by specifically localizing glioblastoma-associated inflammatory processes, providing valuable insights into tumor biology.

Brand ferumoxytol vs. generic ferumoxytol comparison across two dosing regimens: a cardiac MRI image quality study.

BACKGROUND: Ferumoxytol is becoming more widely used as an off-label blood-pool contrast agent for MR angiography (MRA) and four-dimensional (4D) flow imaging in pediatric cardiovascular disease. Brand and generic versions of ferumoxytol are available with no information on relative efficacy as a contrast agent and safety profiles. OBJECTIVE: This study evaluates patient safety and image quality of comparable dosages of generic ferumoxytol (GF) versus brand ferumoxytol (BF) with the following hypotheses: (1) Reducing the contrast dosage from 3 to 2 mg/kg will not affect imaging quality and diagnostic accuracy of MRA and four-dimensional 4D flow. (2) GF and BF have similar image quality. (3) GF and BF have similar patient safety profiles. MATERIALS AND METHODS: In an IRB-approved retrospective study, changes in vitals/clinical status between baseline, during infusion, and 30 min post-infusion were analyzed in 3 groups: group 1 (3 mg/kg BF, 216 patients, age: 19.29 ± 11.71 years ranging from 2 months to 62 years), group 2 (2 mg/kg BF, 47 patients, age: 15.35 ± 8.56 years ranging from 10 days to 41 years), and group 3 (2 mg/kg GF, 127 patients, age: 17.16 ± 12.18 years ranging from 6 days to 58 years). Both pediatric and adult patients with congenital heart disease (CHD) indications were included within the study. Adverse reactions were classified as mild, moderate, or severe. Quantitative analysis of MR image quality was performed with signal-to-noise ratio (SNR) on MRA and velocity-to-noise ratio (VNR) on 4D flow. Qualitative grading of imaging features was performed by 2 experienced observers. Two-way analysis of variance (ANOVA) and chi-square tests were used for comparison with a P value of ≤ 0.05 used for significance. RESULTS: No statistical difference was found in clinical status and vital signs (P>0.05). No severe reactions were reported. 7.9% of GF patients experienced an adverse reaction compared to 2.3% with 3 mg/kg BF and 8.4% with 2 mg/kg BF. There was no statistical difference in SNR between the 3 groups (P>0.05). For 4D flow, 2 mg/kg GF demonstrated an increase in VNR compared to 2 mg/kg BF (P = 0.005). The qualitative scores for MRA and 4D flow were high (≥ 3) across all 3 groups. CONCLUSIONS: No significant difference was identified between 2 mg/kg GF and BF in terms of safety profile and image quality. Given the small sample size of this study, further studies are required to confirm these results.

Guide to use of ferumoxytol for hepatic vascular assessment as part of dual contrast MRI.

Magnetic resonance imaging (MRI) assessment of hepatic vasculature can be challenging in the setting of liver disease and liver lesions. The widely used hepatobiliary contrast agent gadoxetate is an extracellular contrast agent that provides excellent soft tissue characterization but has limitations as a vascular contrast agent. Ferumoxytol is an iron oxide nanoparticle with superparamagnetic properties that can be used as blood pool contrast agent to provide dedicated vascular assessment. We provide a detailed protocol for evaluation of pediatric liver vasculature using ferumoxytol, after imaging of the parenchyma with gadoxetate. We provide multiple examples and discuss practical considerations when incorporating ferumoxytol into practice.

Contemporary sequential segmental approach to congenital heart disease using four-dimensional magnetic resonance imaging with ferumoxytol: an illustrated editorial.

The ferumoxytol-enhanced 4D MR angiography with MUSIC (Multiphase Steady State Imaging with Contrast) technique provides a single data set that captures dynamic cardiovascular anatomy and ventricular function at the same time. Homogeneous opacification of all cardiovascular structures within the imaging volume allows full sequential segmental approach to the congenital heart diseases without any blind spots. The complex systemic and pulmonary venous anatomy is particularly well captured in the MUSIC. Cinematographic display of multiplanar sectional and 3D volume images is helpful in the morphological identification of the cardiac chambers, the assessment of the dynamic nature of the ventricular outflow tracts, and the assessment of the coronary arterial origins and courses.