Four-dimensional Multiphase Steady-State MRI with Ferumoxytol Enhancement: Early Multicenter Feasibility in Pediatric Congenital Heart Disease.

Background The value of MRI in pediatric congenital heart disease (CHD) is well recognized; however, the requirement for expert oversight impedes its widespread use. Four-dimensional (4D) multiphase steady-state imaging with contrast enhancement (MUSIC) is a cardiovascular MRI technique that uses ferumoxytol and captures all anatomic features dynamically. Purpose To evaluate multicenter feasibility of 4D MUSIC MRI in pediatric CHD. Materials and Methods In this prospective study, participants with CHD underwent 4D MUSIC MRI at 3.0 T or 1.5 T between 2014 and 2020. From a pool of 460 total studies, an equal number of MRI studies from three sites (n = 60) was chosen for detailed analysis. With use of a five-point scale, the feasibility of 4D MUSIC was scored on the basis of artifacts, image quality, and diagnostic confidence for intracardiac and vascular connections (n = 780). Respiratory motion suppression was assessed by using the signal intensity profile. Bias between 4D MUSIC and two-dimensional (2D) cine imaging was evaluated by using Bland-Altman analysis; 4D MUSIC examination duration was compared with that of the local standard for CHD. Results A total of 206 participants with CHD underwent MRI at 3.0 T, and 254 participants underwent MRI at 1.5 T. Of the 60 MRI examinations chosen for analysis (20 per site; median participant age, 14.4 months [interquartile range, 2.3-49 months]; 33 female participants), 56 (93%) had good or excellent image quality scores across a spectrum of disease complexity (mean score ± standard deviation: 4.3 ± 0.6 for site 1, 4.9 ± 0.3 for site 2, and 4.6 ± 0.7 for site 3; P < .001). Artifact scores were inversely related to image quality (r = -0.88, P < .001) and respiratory motion suppression (P < .001, r = -0.45). Diagnostic confidence was high or definite in 730 of 780 (94%) intracardiac and vascular connections. The correlation between 4D MUSIC and 2D cine ventricular volumes and ejection fraction was high (range of r = 0.72-0.85; P < .001 for all). Compared with local standard MRI, 4D MUSIC reduced the image acquisition time (44 minutes ± 20 vs 12 minutes ± 3, respectively; P < .001). Conclusion Four-dimensional multiphase steady-state imaging with contrast enhancement MRI in pediatric congenital heart disease was feasible in a multicenter setting, shortened the examination time, and simplified the acquisition protocol, independently of disease complexity. Clinical trial registration no. NCT02752191 © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Roest and Lamb in this issue.

Intermodality feature fusion combining unenhanced computed tomography and ferumoxytol-enhanced magnetic resonance angiography for patient-specific vascular mapping in renal impairment.

OBJECTIVE: The purpose of this study was to establish the feasibility of fusing complementary, high-contrast features from unenhanced computed tomography (CT) and ferumoxytol-enhanced magnetic resonance angiography (FE-MRA) for preprocedural vascular mapping in patients with renal impairment. METHODS: In this Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study, 15 consecutive patients underwent both FE-MRA and unenhanced CT scanning, and the complementary high-contrast features from both modalities were fused to form an integrated, multifeature image. Source images from CT and MRA were segmented and registered. To validate the accuracy, precision, and concordance of fused images to source images, unambiguous landmarks, such as wires from implantable medical devices or indwelling catheters, were marked on three-dimensional (3D) models of the respective modalities, followed by rigid co-registration, interactive fusion, and fine adjustment. We then compared the positional offsets using pacing wires or catheters in the source FE-MRA (defined as points of interest [POIs]) and fused images (n = 5 patients, n = 247 points). Points within 3D image space were referenced to the respective modalities: x (right-left), y (anterior-posterior), and z (cranial-caudal). The respective 3D orthogonal reference axes from both image sets were aligned, such that with perfect registration, a given point would have the same (x, y, z) component values in both sets. The 3D offsets (Δx mm, Δy mm, Δz mm) for each of the corresponding POIs represent nonconcordance between the source FE-MRA and fused images. The offsets were compared using concordance correlation coefficients. Interobserver agreement was assessed using intraclass correlation coefficients and Bland-Altman analyses. RESULTS: Thirteen patients (aged 76 ± 12 years; seven female) with aortic valve stenosis and chronic kidney disease and two patients with thoracoabdominal vascular aneurysms and chronic kidney disease underwent FE-MRA for preprocedural vascular assessment, and unenhanced CT examinations were available in all patients. No ferumoxytol-related adverse events occurred. There were 247 matched POIs evaluated on the source FE-MRA and fused images. In patients with implantable medical devices, the mean offsets in spatial position were 0.31 ± 0.51 mm (ρ = 0.99; Cb = 1; 95% confidence interval [CI], 0.99-0.99) for Δx, 0.27 ± 0.69 mm (ρ = 0.99; Cb = 0.99; 95% CI, 0.99-0.99) for Δy, and 0.20 ± 0.59 mm (ρ = 1; Cb = 1; 95% CI, 0.99-1.00) for Δz. Interobserver agreement was excellent (intraclass correlation coefficient, >0.99). The mean difference in offset between readers was 1.5 mm. CONCLUSIONS: Accurate 3D feature fusion is feasible, combining luminal information from FE-MRA with vessel wall information on unenhanced CT. This framework holds promise for combining the complementary strengths of magnetic resonance imaging and CT to generate information-rich, multifeature composite vascular images while avoiding the respective risks and limitations of both modalities.

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.

Ferumoxytol-enhanced MR Angiography for Vascular Access Mapping before Transcatheter Aortic Valve Replacement in Patients with Renal Impairment: A Step Toward Patient-specific Care.

Purpose To assess the technical feasibility of the use of ferumoxytol-enhanced (FE) magnetic resonance (MR) angiography for vascular mapping before transcatheter aortic valve replacement in patients with renal impairment. Materials and Methods This was an institutional review board-approved and HIPAA-compliant study. FE MR angiography was performed at 3.0 T or 1.5 T. Unenhanced computed tomographic (CT) images were used to overlay vascular calcification on FE MR angiographic images as composite fused three-dimensional data. Image quality of the subclavian and aortoiliofemoral arterial tree and confidence in the assessment of calcification were evaluated by using a four-point scale (4 = excellent vascular definition or strong confidence). Signal intensity nonuniformity as reflected by the heterogeneity index (ratio between the mean standard deviation of luminal signal intensity and the mean luminal signal intensity), signal-to-noise ratio, and consistency of luminal diameter measurements were quantified. Findings at FE MR angiography were compared with pelvic angiograms. Results Twenty-six patients underwent FE MR angiography without adverse events. A total of 286 named vascular segments were scored. The image quality score was 4 for 99% (283 of 286) of the segments (κ = 0.9). There was moderate to strong confidence in the ability to assess vascular calcific morphology in all studies with complementary unenhanced CT. The steady-state luminal heterogeneity index was low, and signal-to-noise ratio was high. Interobserver luminal measurements were reliable (intraclass correlation coefficient, 0.98; 95% confidence interval: 0.98, 0.99). FE MR angiographic findings were consistent with correlative pelvic angiograms in all 16 patients for whom the latter were available. Conclusion In patients with renal impairment undergoing transcatheter aortic valve replacement, FE MR angiography is technically feasible and offers reliable vascular mapping without exposure to iodine- or gadolinium-based contrast agents. Thus, the total cumulative dose of iodine-based contrast material is minimized and the risk of acute nephropathy is reduced. © RSNA, 2017 Online supplemental material is available for this article.

Ferumoxytol enhanced black-blood cardiovascular magnetic resonance imaging.

BACKGROUND: Bright-blood and black-blood cardiovascular magnetic resonance (CMR) techniques are frequently employed together during a clinical exam because of their complementary features. While valuable, existing black-blood CMR approaches are flow dependent and prone to failure. We aim to assess the effectiveness and reliability of ferumoxytol enhanced (FE) Half-Fourier Single-shot Turbo Spin-echo (HASTE) imaging without magnetization preparation pulses to yield uniform intra-luminal blood signal suppression by comparing FE-HASTE with pre-ferumoxytol HASTE imaging. METHODS: This study was IRB-approved and HIPAA compliant. Consecutive patients who were referred for FE-CMR between June 2013 and February 2017 were enrolled. Qualitative image scores reflecting the degree and reliability of blood signal suppression were based on a 3-point Likert scale, with 3 reflecting perfect suppression. For quantitative evaluation, homogeneity indices (defined as standard deviation of the left atrial signal intensity) and signal-to-noise ratios (SNR) for vascular lumens and cardiac chambers were measured. RESULTS: Of the 340 unique patients who underwent FE-CMR, HASTE was performed in 257. Ninety-three patients had both pre-ferumoxytol HASTE and FE-HASTE, and were included in this analysis. Qualitative image scores reflecting the degree and reliability of blood signal suppression were significantly higher for FE-HASTE images (2.9 [IQR 2.8-3.0] vs 1.8 [IQR 1.6-2.1], p < 0.001). Inter-reader agreement was moderate (k = 0.50, 95% CI 0.45-0.55). Blood signal suppression was more complete on FE-HASTE images than on pre-ferumoxytol HASTE, as indicated by lower mean homogeneity indices (24.5 [IQR 18.0-32.8] vs 108.0 [IQR 65.0-170.4], p < 0.001) and lower blood pool SNR for all regions (5.6 [IQR 3.2-10.0] vs 21.5 [IQR 12.5-39.4], p < 0.001). CONCLUSION: FE-HASTE black-blood imaging offers an effective, reliable, and simple approach for flow independent blood signal suppression. The technique holds promise as a fast and routine complement to bright-blood cardiovascular imaging with ferumoxytol.