Gadofosveset Research Articles

High-resolution three\u2011dimensional contrast\u2011enhanced magnetic resonance venography in children: comparison of gadofosveset trisodium with ferumoxytol

BackgroundGadofosveset is a gadolinium-based blood pool contrast agent that was approved by the United States Food and Drug Administration in 2008. Its unanticipated withdrawal from production in 2016 created a void in the blood pool agent inventory and highlighted the need for an alternative agent with comparable imaging properties.ObjectiveThe purpose of our study is to compare the diagnostic image quality, vascular contrast-to-noise ratio (CNR) and temporal signal characteristics of gadofosveset trisodium and ferumoxytol at similar molar doses for high-resolution, three-dimensional (3-D) magnetic resonance (MR) venography in children.Materials and methodsThe medical records and imaging data sets of patients who underwent high-resolution 3-D gadofosveset-enhanced MR venography (GE-MRV) or ferumoxytol-enhanced MR venography (FE-MRV) were retrospectively reviewed. Two groups of 20 pediatric patients (age- and weight-matched with one patient common to both groups; age range: 2 days–15 years) who underwent high-resolution 3-D GE-MRV or FE-MRV at similar molar doses were identified and analyzed. Qualitative analysis of image quality and vessel definition was performed by two blinded pediatric radiologists. Interobserver agreement was assessed with the AC1 (first-order agreement coefficient) statistic. Signal-to-noise ratio (SNR) and CNR of the inferior vena cava and aorta were measured in the steady-state venous phase. Medical records were retrospectively reviewed for any adverse reactions associated with either contrast agent.ResultsMeasured SNR and CNR of the inferior vena cava were higher for FE-MRV than GE-MRV (P = 0.034 and P < 0.001, respectively). The overall image quality score and individual vessel scores of FE-MRV were equal to or greater than GE-MRV (P = 0.084), with good interobserver agreement (AC1 = 0.657). The venous signal on FE-MRV was stable over the longest interval measured (1 h, 13 min and 46 s), whereas venous signal on GE-MRV showed more variability and earlier loss of signal. No adverse reactions were noted in any patient with either contrast agent.ConclusionFerumoxytol produces more uniform and stable enhancement throughout the entire venous circulation in children than gadofosveset, offering a wider time window for optimal image acquisition. FE-MRV offers a near-ideal approach to high-resolution venography in children at all levels of anatomical complexity.

Technique and protocols for cardiothoracic time-resolved contrast-enhanced magnetic resonance angiography sequences: a systematic review

To review contrast medium administration protocols used for cardiothoracic applications of time-resolved, contrast-enhanced magnetic resonance angiography (MRA) sequences. A systematic search of the literature (Medline/EMBASE) was performed to identify articles utilising time-resolved MRA sequences, focusing on type of sequence, adopted technical parameters, contrast agent (CA) issues, and acquisition workflow. Study design, year of publication, population, magnetic field strength, type, dose, and injection parameters of CA, as well as technical parameters of time-resolved MRA sequences were extracted. Of 117 retrieved articles, 16 matched the inclusion criteria. The study design was prospective in 9/16 (56%) articles, and study population ranged from 5 to 185 patients, for a total of 506 patients who underwent cardiothoracic time-resolved MRA. Magnetic field strength was 1.5 T in 13/16 (81%), and 3 T in 3/16 (19%) articles. The administered CA was gadobutrol (Gadovist) in 6/16 (37%) articles, gadopentetate dimeglumine (Magnevist) in 5/16 (31%), gadobenate dimeglumine (MultiHance) in 2/16 (13%), gadodiamide (Omniscan) in 2/16 (13%), gadofosveset trisodium (Ablavar, previously Vasovist) in 1/16 (6%). CA showed highly variable doses among studies: fixed amount or based on patient body weight (0.02-0.2 mmol/kg) and was injected with a flow rate ranging 1-5 ml/s. Sequences were TWIST in 13/16 (81%), TRICKS in 2/16 (13%), and CENTRA 1/16 articles (6%). Time-resolved MRA sequences were adopted in different clinical settings with a large spectrum of technical approaches, mostly in association with different CA dose, type, and injection method. Further studies in relation to specific clinical indications are warranted to provide a common standardised acquisition protocol.

Creating three dimensional models of the right ventricular outflow tract: influence of contrast, sequence, operator, and threshold.

The use of 3D printed models of the right ventricular outflow tract (RVOT) for surgical and interventional planning is growing and often requires image segmentation of cardiac magnetic resonance (CMR) images. Segmentation results may vary based on contrast, image sequence, signal threshold chosen by the operator, and manual post-processing. The purpose of this study was to determine potential biases and post-processing errors in image segmentation to enable informed decisions. Models of the RVOT and pulmonary arteries from twelve patients who had contrast enhanced CMR angiography with gadopentetate dimeglumine (GPD), gadofosveset trisodium (GFT), and a post-GFT inversion-recovery (IR) whole heart sequence were segmented, trimmed, and aligned by three operators. Geometric agreement and minimal RVOT diameters were compared between sequences and operators. To determine the contribution of threshold, interoperator variability was compared between models created by the same two operators using the same versus different thresholds. Geometric agreement by Dice between objects was high (intraoperator: 0.89-0.95; interoperator: 0.95-0.97), without differences between sequences. Minimal RVOT diameters differed on average by - 1.9 to - 1.3mm (intraoperator) and by 0.4 to 1.4mm (interoperator). The contribution of threshold to interoperator geometric agreement was not significant (same threshold: 0.96 ± 0.06, different threshold: 0.93 ± 0.05; p = 0.181), but minimal RVOT diameters were more variable with different versus constant thresholds (- 9.12% vs. 2.42%; p < 0.05). Thresholding does not significantly change interoperator variability for geometric agreement, but does for minimal RVOT diameter. Minimal RVOT diameters showed clinically relevant variation within and between operators.

Magnetic resonance angiography imaging of pulmonary embolism using agents with blood pool properties as an alternative to computed tomography to avoid radiation exposure

PurposeTo evaluate the feasibility and accuracy of a combined magnetic resonance angiography (MRA) - magnetic resonance venography (MRV) protocol using contrast agents with blood pool properties, gadofosveset trisodium and gadobenate dimeglumine, in the evaluation of pulmonary embolus (PE) and deep venous thrombosis (DVT) as compared to the standard clinical reference imaging modalities; computed tomography pulmonary angiography (CTPA) and color-coded Duplex ultrasound (DUS). Materials and methodsThis prospective clinical study recruited patients presenting to the emergency department with clinical suspicion for PE and scheduled for a clinically indicated CTPA. We performed both MRA of the chest for the evaluation of PE as well as MRV of the pelvis and thighs to evaluate for DVT using a single contrast injection. MRA-MRV data was compared to the clinical reference standard CTPA and DUS, respectively. ResultsA total of 40 patients were recruited. The results on a per-patient basis comparing MRA to CTPA for pulmonary embolus yielded 100% sensitivity and 97% specificity. There was a small subset of patients that underwent clinical DUS to evaluate for DVT, which demonstrated a sensitivity and specificity of 100% for MRV. ConclusionsThis single-center, preliminary study using contrast agents with blood pool properties to perform a relatively rapid combined MRA-MRV exam to image for PE and above knee DVT shows potential as an alternative imaging choice to CTPA. Further large-scale, multicentre studies are warranted.

Frequency and Severity of Acute Allergic-Like Reactions to Intravenously Administered Gadolinium-Based Contrast Media in Children.

The purpose of this study is to determine the frequency and severity of acute allergic-like reactions to gadolinium-based contrast media (GBCM) in children before, during, and after the transition from gadopentetate dimeglumine to gadoterate meglumine as our primary clinical GBCM. Institutional review board approval was obtained for this Health Insurance Portability and Accountability Act-compliant retrospective investigation. Allergic-like reactions to GBCM in pediatric patients were retrospectively assessed from January 2009 to January 2017, which included a departmental change of GBCM from gadopentetate dimeglumine to gadoterate meglumine. Allergic-like reactions were identified from departmental and hospital databases. The number of doses of GBCM was obtained from billing data. Allergic-like reaction frequencies for each GBCM were calculated and compared using the chi-squared test. A total of 32,365 administrations of GBCM occurred during the study period (327 for gadofosveset trisodium; 672 for gadoxetate disodium; 12,012 for gadoterate meglumine; and 19,354 for gadopentetate dimeglumine). Allergic-like reactions occurred after 21 (0.06%) administrations. Reaction frequencies were not significantly different among the GBCM (0.3% gadofosveset trisodium; 0% gadoxetate disodium, 0.06% gadoterate meglumine, 0.08% gadopentetate dimeglumine; P > 0.05). Ten (47.6%) reactions were mild, 10 (47.6%) were moderate, and 1 (4.8%) was severe. The overall reaction frequency peaked during the 6-month transition period from gadopentetate dimeglumine to gadoterate meglumine (0.20%), compared with 0.07% pretransition (P = 0.048) and 0.04% posttransition (P = 0.0095). Allergic-like reactions to GBCM in children are rare. Gadoterate meglumine has a reaction frequency that does not significantly differ from other GBCMs. During the transition from gadopentetate dimeglumine to gadoterate meglumine, an increase in the frequency of reported allergic-like reactions was observed, likely reflective of the Weber effect.

Myocardial T1 mapping and determination of partition coefficients at 3 tesla: comparison between gadobenate dimeglumine and gadofosveset trisodium.

ObjectiveTo compare an albumin-bound gadolinium chelate (gadofosveset trisodium) and an extracellular contrast agent (gadobenate dimeglumine), in terms of their effects on myocardial longitudinal (T1) relaxation time and partition coefficient.Materials and MethodsStudy subjects underwent two imaging sessions for T1 mapping at 3 tesla with a modified look-locker inversion recovery (MOLLI) pulse sequence to obtain one pre-contrast T1 map and two post-contrast T1 maps (mean 15 and 21 min, respectively). The partition coefficient was calculated as ΔR1myocardium /ΔR1blood , where R1 is 1/T1.ResultsA total of 252 myocardial and blood pool T1 values were obtained in 21 healthy subjects. After gadolinium administration, the myocardial T1 was longer for gadofosveset than for gadobenate, the mean difference between the two contrast agents being −7.6 ± 60 ms (p = 0.41). The inverse was true for the blood pool T1, which was longer for gadobenate than for gadofosveset, the mean difference being 56.5 ± 67 ms (p < 0.001). The partition coefficient (λ) was higher for gadobenate than gadofosveset (0.41 vs. 0.33), indicating slower blood pool washout for gadofosveset than for gadobenate.ConclusionMyocardial T1 times did not differ significantly between gadobenate and gadofosveset. At typical clinical doses of the contrast agents, partition coefficients were significantly lower for the intravascular contrast agent than for the extravascular agent.

Review of hepatobiliary contrast agents: Current applications and challenges.

Review of hepatobiliary contrast agents: Current applications and challenges.

Diagnostic performance of gadofosveset-enhanced axillary MRI for nodal (re)staging in breast cancer patients: results of a validation study

To evaluate diagnostic performance of gadofosveset (GDF)-enhanced magnetic resonance imaging (MRI) in addition to T2-weighted (T2W) MRI for nodal (re)staging in newly diagnosed breast cancer patients. Ninety patients underwent axillary T2W- and GDF-MRI. Two radiologists independently scored each lymph node; first on T2W-MRI, subsequently adjusting their score on GDF-MRI. Diagnostic performance parameters were calculated on node-by-node and patient-by-patient validation with histopathology as the reference standard. Furthermore, learning curve analysis for reading GDF-MRI was performed. In patient-by-patient validation, overall reader performances for T2W- and GDF-MRI were similar with area under the receiver operating characteristic curves (AUC) of 0.75 and 0.77 (p=0.731) for reader 1 and 0.79 and 0.72 (p=0.156) for reader 2. For node-by-node validation, AUC values of T2W- and GDF-MRI were 0.76 and 0.82 (p=0.018) and 0.77 and 0.77 (p=0.998) for reader 1 and 2. The AUC for reader 1 was 0.71 for first one-third of nodes evaluated, improving to 0.80 and 0.95 for the next and last one-third, respectively. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) improved from 38%, 89%, 56%, and 79% to 60%, 93%, 64%, and 92%. The AUC of reader 2 improved from 0.69 to 0.79. The present study confirmed that GDF-MRI, in addition to T2W-MRI, has potential as a non-invasive method for nodal (re)staging in breast cancer.

Validation of Blood Volume Fraction Quantification with 3D Gradient Echo Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Porcine Skeletal Muscle.

The purpose of this study was to assess the accuracy of fractional blood volume (vb) estimates in low-perfused and low-vascularized tissue using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The results of different MRI methods were compared with histology to evaluate the accuracy of these methods under clinical conditions. vb was estimated by DCE-MRI using a 3D gradient echo sequence with k-space undersampling in five muscle groups in the hind leg of 9 female pigs. Two gadolinium-based contrast agents (CA) were used: a rapidly extravasating, extracellular, gadolinium-based, low-molecular-weight contrast agent (LMCA, gadoterate meglumine) and an extracellular, gadolinium-based, albumin-binding, slowly extravasating blood pool contrast agent (BPCA, gadofosveset trisodium). LMCA data were evaluated using the extended Tofts model (ETM) and the two-compartment exchange model (2CXM). The images acquired with administration of the BPCA were used to evaluate the accuracy of vb estimation with a bolus deconvolution technique (BD) and a method we call equilibrium MRI (EqMRI). The latter calculates the ratio of the magnitude of the relaxation rate change in the tissue curve at an approximate equilibrium state to the height of the same area of the arterial input function (AIF). Immunohistochemical staining with isolectin was used to label endothelium. A light microscope was used to estimate the fractional vascular area by relating the vascular region to the total tissue region (immunohistochemical vessel staining, IHVS). In addition, the percentage fraction of vascular volume was determined by multiplying the microvascular density (MVD) with the average estimated capillary lumen, , where d = 8μm is the assumed capillary diameter (microvascular density estimation, MVDE). Except for ETM values, highly significant correlations were found between most of the MRI methods investigated. In the cranial thigh, for example, the vb medians (interquartile range, IQRs) of IHVS, MVDE, BD, EqMRI, 2CXM and ETM were vb = 0.7(0.3)%, 1.1(0.4)%, 1.1(0.4)%, 1.4(0.3)%, 1.2(1.8)% and 0.1(0.2)%, respectively. Variances, expressed by the difference between third and first quartiles (IQR) were highest for the 2CXM for all muscle groups. High correlations between the values in four muscle groups—medial, cranial, lateral thigh and lower leg - estimated with MRI and histology were found between BD and EqMRI, MVDE and 2CXM and IHVS and ETM. Except for the ETM, no significant differences between the vb medians of all MRI methods were revealed with the Wilcoxon rank sum test. The same holds for all muscle regions using the 2CXM and MVDE. Except for cranial thigh muscle, no significant difference was found between EqMRI and MVDE. And except for the cranial thigh and the lower leg muscle, there was also no significant difference between the vb medians of BD and MVDE. Overall, there was good vb agreement between histology and the BPCA MRI methods and the 2CXM LMCA approach with the exception of the ETM method. Although LMCA models have the advantage of providing excellent curve fits and can in principle determine more physiological parameters than BPCA methods, they yield more inaccurate results.

Correlation between quantitative and semiquantitative parameters in DCE-MRI with a blood pool agent in rectal cancer: can semiquantitative parameters be used as a surrogate for quantitative parameters?

The aim of this study was to assess correlation between quantitative and semiquantitative parameters in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in rectal cancer patients, both in a primary staging and restaging setting. Nineteen patients were included with DCE-MRI before and/or after neoadjuvant therapy. DCE-MRI was performed with gadofosveset trisodium (Ablavar®, Lantheus Medical Imaging, North Billerica, Massachusetts, USA). Regions of interest were placed in the tumor and quantitative parameters were extracted with Olea Sphere 2.2 software permeability module using the extended Tofts model. Semiquantitative parameters were calculated on a pixel-by-pixel basis. Spearman rank correlation tests were used for assessment of correlation between parameters. A p value ≤0.05 was considered statistically significant. Strong positive correlations were found between mean peak enhancement and mean K trans: 0.79 (all patients, p<0.0001), 0.83 (primary staging, p=0.003), and 0.81 (restaging, p=0.054). Mean wash-in correlated significantly with mean V p and K ep (0.79 and 0.58, respectively, p<0.0001 and p=0.009) in all patients. Mean wash-in showed a significant correlation with mean K ep (0.67, p=0.033) in the primary staging group. On the restaging MRI, mean wash-in only strongly correlated with mean V p (0.81, p=0.054). This study shows a strong correlation between quantitative and semiquantitative parameters in DCE-MRI for rectal cancer. Peak enhancement correlates strongly with K trans and wash-in showed strong correlation with V p and K ep. These parameters have been reported to predict tumor aggressiveness and response in rectal cancer. Therefore, semiquantitative analyses might be a surrogate for quantitative analyses.

Superior Abdominal 4D Flow MRI Data Consistency with Adjusted Preprocessing Workflow and Noncontrast Acquisitions

To assess the impact of an alternative preprocessing workflow on noncontrast- and contrast-enhanced abdominal four-dimensional flow magnetic resonance imaging (4D flow MRI) data consistency. Twenty patients with cirrhosis and portal hypertension (5 women; 53 ± 10 years old) underwent 4D flow MRI at 3.0T before and after administration of 0.03 mmol/kg of gadofosveset trisodium with velocity sensitivities of 100 and 50 cm/s for arterial and venous flow quantifications, respectively. 4D flow MRI data were preprocessed using the conventional workflow (workflow 1), applying noise filters prior to eddy current correction, and an alternative workflow (workflow 2), first correcting for eddy currents and using noise filtering only if needed for anti-aliasing. Vessel segmentation quality was ranked by independent reviewers and compared via Wilcoxon signed-rank tests. Flow quantification and conservation of mass at two portal and one arterial branch points were compared via paired t tests. Segmentation quality was significantly higher for workflow 2 (P < 0.05) with excellent interobserver agreement (κ = 0.92). Workflow 2 resulted in larger flow values (P < 0.05) with improved conservation of mass (7.3 ± 6.1% vs. 27.7 ± 25.0%, P < 0.001 [portal]; 10.7 ± 9.0% vs. 21.7 ± 21.6%, P = 0.02 [arterial]). Peak velocities and abdominal aortic flow were similar (P > 0.05). Noncontrast acquisitions yielded significantly smaller portal flow values (P < 0.05) with improved conservation of mass (5.8 ± 4.7% vs. 8.7 ± 6.9%, P = 0.05 [portal]; 6.2 ± 4.5% vs. 13.7 ± 10.2%, P = 0.03 [arterial]). Superior abdominal 4D flow MRI data consistency was obtained by applying eddy current correction before any other data manipulation, using noise masking and velocity anti-aliasing cautiously, and using noncontrast acquisitions.

A novel blood-pooling MR contrast agent: Carboxymethyl-diethylaminoethyl dextran magnetite

Gadofosveset trisodium is available as a prolonged pooling vascular contrast agent for magnetic resonance imaging. As gadolinium (Gd)-based agents may increase the risk for nephrogenic systemic fibrosis in patients with severe renal insufficiency, the present study synthesized carboxymethyl-diethylaminoethyl dextran magnetite (CMEADM) particles as a blood-pooling, non-Gd‑based contrast agent. CMEADM particles carry a negative or positive charge due to the binding of amino and carboxyl groups to the hydroxyl group of dextran. The present study evaluated whether the degree of charge alters the blood‑pooling time. The evaluation was performed by injecting four groups of three Japanese white rabbits each with CMEADM‑, CMEADM2‑, CMEADM+ (surface charges:‑10.4, ‑41.0 and +9.6mV, respectively) or with ultrasmall superparamagnetic iron oxide (USPIO; ‑11.5mV). The relative signal intensity (SIrel) of each was calculated using the following formula: SIrel=(SI post‑contrast‑SI pre‑contrast/SI pre‑contrast)x100. Following injection with the CMEADMs, but not with USPIO, the invivo pooling time was prolonged to >300min. No significant differences were attributable to the electric charge among the CMEADM‑, CMEADM2‑ or and CMEADM+ particles when analyzed with analysis of variance and Tukey's HSD test. Taken together, all three differently‑charged CMEADM2 particles exhibited prolonged vascular enhancing effects, compared with the USPIO. The degree of charge of the contrast agents used in the present study did not result in alteration of the prolonged blood pooling time.

Combined blood pool and extracellular contrast agents for pediatric and young adult cardiovascular magnetic resonance imaging.

A comprehensive cardiac magnetic resonance (cardiac MR) study including both late gadolinium enhancement (LGE) and MR angiography may be indicated for patients with a history of acquired or congenital heart disease. To study the novel use of an extracellular agent for assessment of LGE combined with a blood pool contrast agent for detailed MR angiography evaluation to yield a comprehensive cardiac MR study in these patients. We reviewed clinical cardiac MR studies utilizing extracellular and blood pool contrast agents and noted demographics, clinical data and adverse events. We rated LGE image quality and MR angiography image quality for each vascular segment and calculated inter-rater variability. We also quantified contrast-to-noise ratio (CNR). Thirty-three patients (mean age 13.9 ± 3years) received an extracellular contrast agent (10 gadobenate dimeglumine, 23 gadopentetate dimeglumine) and blood pool contrast agent (33 gadofosveset trisodium). No adverse events were reported. MRI indications included Kawasaki disease (8), cardiomyopathy and coronary anatomy (15), repaired congenital heart disease (8), and other (2). Mean LGE quality was 2.6 ± 0.6 with 97% diagnostic imaging. LGE quality did not vary by type of contrast agent given (P = 0.07). Mean MR angiography quality score was 4.7 ± 0.6, with high inter-rater agreement (k = 0.6-0.8, P < 0.002). MR angiography quality did not vary by type of contrast agent used (P = 0.6). Cardiac MR studies utilizing both extracellular and blood pool contrast agents are feasible and safe and provide excellent-quality LGE and MR angiography images. The use of two contrast agents allows for a comprehensive assessment of both myocardial viability and vascular anatomy during the same exam.

Safety and Efficacy of A High Performance Graphene-Based Magnetic Resonance Imaging Contrast Agent for Renal Abnormalities.

The etiology of renal insufficiency includes primary (e.g polycystic kidney disease) or secondary (e.g. contrast media, diabetes) causes. The regulatory restrictions placed on the use of contrast agents (CAs) for non-invasive imaging modalities such as X-ray computed tomography (CT) and magnetic resonance imaging (MRI) affects the clinical management of these patients. With the goal to develop a next-generation CA for unfettered use for renal MRI, here we report, in a rodent model of chronic kidney disease, the preclinical safety and efficacy of a novel nanoparticle CA comprising of manganese (Mn2+) ions intercalated graphene coated with dextran (hereafter called Mangradex). Nephrectomized rats received single or 5 times/week repeat (2 or 4 weeks) intravenous (IV) injections of Mangradex at two potential (low = 5 mg/kg, and high = 50 mg/kg) therapeutic doses. Histopathology results indicate that Mangradex does not elicit nephrogenic systemic fibrosis (NSF)-like indicators or questionable effects on vital organs of rodents. MRI at 7 Tesla magnetic field was performed on these rats immediately after IV injections of Mangradex at one potential therapeutic dose (25 mg/kg, [Mn2+] = 60 nmoles/kg) for 90 minutes. The results indicated significant (>100%) and sustained contrast enhancement in the kidney and renal artery at these low paramagnetic ion (Mn2+) concentration; 2 orders of magnitude lower than the paramagnetic ion concentration in a typical clinical dose of long circulating Gd3+-based MRI CA gadofosveset trisodium. The results open avenues for further development of Mangradex as a MRI CA to diagnose and monitor abnormalities in renal anatomy and vasculature.

Combined gadoxetic acid and gadofosveset enhanced liver MRI for detection and characterization of liver metastases.

To compare gadoxetic acid alone and combined gadoxetic acid/gadofosveset trisodium-enhanced liver MRI for detection of metastases and differentiation of metastases from haemangiomas. Ninety-one patients underwent gadoxetic acid-enhanced liver MRI before and after additional injection of gadofosveset. First, two readers retrospectively identified metastases on gadoxetic acid alone enhanced delayed hepatobiliary phase T1-weighted images together with all other MR images (dynamic images, T2-weighted images, diffusion-weighted images). Second, readers assessed additional T1-weighted images obtained after administration of gadofosveset trisodium. For both interpretations, readers rated lesion conspicuity and confidence in differentiating metastases from haemangiomas. Results were compared using alternative free-response receiver-operating characteristic (AFROC) and conventional ROC methods. Histology and follow-up served as reference standard. There were 145 metastases and 16 haemangiomas. Both readers detected more metastases using combined gadoxetic acid/gadofosveset (reader 1 = 130; reader 2 = 124) compared to gadoxetic acid alone (reader 1 = 104; reader 2 = 103). Sensitivity of combined gadoxetic acid/gadofosveset (reader 1 = 90%; reader 2 = 86%) was higher than that of gadoxetic acid alone (reader 1 = 72%; reader 2 = 71%, both P < 0.01). AFROC-AUC was higher for the combined technique (0.92 vs. 0.86, P < 0.001). Sensitivity for correct differentiation of metastases from haemangiomas was higher for the combined technique (reader 1 = 98%; reader 2 = 99% vs. reader 1 = 86%; reader 2 = 91%, both P < 0.01). ROC-AUC was significantly higher for the combined technique (reader 1 = 1.00; reader 2 = 1.00 vs. reader 1 = 0.87; reader 2 = 0.92, both P < 0.01). Combined gadoxetic acid/gadofosveset-enhanced MRI improves detection and characterization of liver metastases compared to gadoxetic acid alone. • Combined gadoxetic acid and gadofosveset-enhanced liver MRI significantly improves detection of metastases. • The combined enhancement technique improves the accuracy to differentiate metastases from haemangiomas. • Prospective studies need to determine the clinical impact of the combined technique.

MRI with gadofosveset trisodium (Ablavar™) in the Preoperative patient with colorectal liver metastases is a useful problem-solving tool for difficult-to-diagnose lesions

MRI with gadofosveset trisodium (Ablavar™) in the Preoperative patient with colorectal liver metastases is a useful problem-solving tool for difficult-to-diagnose lesions

Improved high-resolution pediatric vascular cardiovascular magnetic resonance with gadofosveset-enhanced 3D respiratory navigated, inversion recovery prepared gradient echo readout imaging compared to 3D balanced steady-state free precession readout imaging

BackgroundImproved delineation of vascular structures is a common indication for cardiovascular magnetic resonance (CMR) in children and requires high spatial resolution. Currently, pre-contrast 3D, respiratory navigated, T2-prepared, fat saturated imaging with a bSSFP readout (3D bSSFP) is commonly used; however, these images can be limited by blood pool inhomogeneity and exaggeration of metal artifact. We compared image quality of pediatric vasculature obtained using standard 3D bSSFP to 3D, respiratory navigated, inversion recovery prepared imaging with a gradient echo readout (3D IR GRE) performed after administration of gadofosveset trisodium (GT), a blood pool contrast agent.MethodsFor both sequences, VCG triggering was used with acquisition during a quiescent period of the cardiac cycle. 3D bSSFP imaging was performed pre-contrast, and 3D IR GRE imaging was performed 5 min after GT administration. We devised a vascular imaging quality score (VIQS) with subscores for coronary arteries, pulmonary arteries and veins, blood pool homogeneity, and metal artifact. Scoring was performed on axial reconstructions of isotropic datasets by two independent readers and differences were adjudicated. Signal- and contrast-to-noise (SNR and CNR) calculations were performed on each dataset.ResultsThirty-five patients had both 3D bSSFP and 3D IR GRE imaging performed. 3D IR GRE imaging showed improved overall vascular imaging compared to 3D bSSFP when comparing all-patient VIQS scores (n = 35, median 14 (IQR 11–15), vs 6 (4–10), p < 0.0001), and when analyzing the subset of patients with intrathoracic metal (n = 17, 16 (14–17) vs. 5 (2–9), p < 0.0001). 3D IR GRE showed significantly improved VIQS subscores for imaging the RCA, pulmonary arteries, pulmonary veins, and blood pool homogeneity. In addition, 3D IR GRE imaging showed reduced variability in both all-patient and metal VIQS scores compared to 3D bSSFP (p < 0.05). SNR and CNR were higher with 3D IR GRE in the left ventricle and left atrium, but not the pulmonary arteries.ConclusionsRespiratory navigated 3D IR GRE imaging after GT administration provides improved vascular CMR in pediatric patients compared to pre-contrast 3D bSSFP imaging, as well as improved imaging in patients with intrathoracic metal. It is an excellent alternative in this challenging patient population when high spatial resolution vascular imaging is needed.

Imaging insights from the bifurcated Y-graft Fontan procedure

Results From August, 2010 to July, 2015, 45 children (median age 3.6 years, range 1.5 18.9 years) have undergone a Y-graft Fontan. In all 45 patients, echocardiography was unable to visualize the Y-arm connections to the branch PA’s. Thirty-nine patients underwent CMR a median of 9 days after Fontan (range 4-295 days), and 6 patients with pacemakers underwent CTA. Early in the experience, time resolved contrast enhanced magnetic resonance angiogram (CEMRA) provided the best spatial resolution for baffle evaluation (Figure 1a). In late 2013, our CMR protocol changed to include a blood pool Gadolinium contrast agent, Gadofosveset Trisodium. Subsequently, postcontrast, 3D, respiratory navigated, inversion recovery gradient echo imaging (3D IR GRE) provided superior spatial resolution for the final 19 children (Figure 1b). In one patient, thrombosis in the baffle was found. In 40 patients, some degree of stenosis was found in a Fontan baffle or branch PA, though most were mild (n = 27). Among those with moderate or severe stenosis, most occurred in the central PA, between the insertion of the bidirectional Glenn (BDG) and a Y-arm (n = 7). Phase contrast imaging and the time resolved CEMRA provided insights into Fontan hemodynamics. In 14 patients, inferior systemic venous return was affected by the BDG position and angulation, with competitive flow in either the left or right Y-arm resulting in asymmetric inferior systemic venous return to the branch PA’s (Figure 2). This finding was more pronounced in patients with central PA stenosis.

A clinical combined gadobutrol bolus and slow infusion protocol enabling angiography, inversion recovery whole heart, and late gadolinium enhancement imaging in a single study.

BackgroundThe use of gadolinium contrast agents in cardiovascular magnetic resonance is well-established and serves to improve both vascular imaging as well as enable late gadolinium enhancement (LGE) imaging for tissue characterization. Currently, gadofosveset trisodium, an intravascular contrast agent, combined with a three-dimensional inversion recovery balanced steady state free precession (3D IR bSSFP) sequence, is commonly used in pediatric cardiac imaging and yields excellent vascular imaging, but cannot be used for late gadolinium enhancement. Gadofosveset use remains limited in clinical practice, and manufacture was recently halted, thus an alternative is needed to allow 3D IR bSSFP and LGE in the same study.MethodsHere we propose a protocol to give a bolus of 0.1 mL/kg = 0.1 mmol/kg gadobutrol (GADAVIST/GADOVIST) for time-resolved magnetic resonance angiography (MRA). Subsequently, 0.1 mmol/kg is diluted up to 5 or 7.5 mL with saline and then loaded into intravenous tubing connected to the patient. A 0.5 mL short bolus is infused, then a slow infusion is given at 0.02 or 0.03 mL/s. Image navigated (iNAV) 3D IR bSSFP imaging is initiated 45–60 s after the initiation of the infusion, with a total image acquisition time of ~5 min. If necessary, LGE imaging using phase sensitive inversion recovery reconstruction (PSIR) is performed at 10 min after the infusion is initiated.ResultsWe have successfully performed the above protocol with good image quality on 10 patients with both time-resolved MRA and 3D IR bSSFP iNAV imaging. Our initial attempts to use pencil beam respiratory navigation failed due to signal labeling in the liver by the navigator. We have also performed 2D PSIR LGE successfully, with both LGE positive and LGE negative results.ConclusionA bolus of gadobutrol, followed later by a slow infusion, allows time-resolved MRA, 3D IR bSSFP using the iNAV navigation technique, and LGE imaging, all in a single study with a single contrast agent.

Part 1 – Coronary angiography with gadofosveset trisodium: a prospective feasibility study evaluating injection techniques for steady-state imaging

BackgroundThe purpose of this study was to define an optimal injection protocol for 5–10 min duration navigator-based coronary MR angiography using an intravascular gadolinium-based contrast agent (GBCA), which is better suited for steady-state coronary MR angiography than conventional GBCAs.MethodsUsing projections from pharmacokinetic models of the intravascular concentration of gadofosveset, a dual-injection protocol was formulated and tested on 14 healthy human subjects. Modified Look-Locker inversion recovery (MOLLI) sequences were used for T1 mapping at 3 Tesla to evaluate the concentration of tracer in the aorta over the scanning interval.ResultsPharmacokinetic models for a bolus plus slow infusion technique at a 5, 10, and 15 min steady state intravascular concentration was compared to single bolus curves. The 70 %/30 % bolus/slow infusion technique resulted in the highest intravascular concentration over a 5 min scan duration. Similarly, the 60 %/40 % bolus/slow infusion technique was projected to be ideal for image acquisition duration of 5–10 min. These models were confirmed with T1 maps on normal volunteers. Arterial-venous mixing of contrast was achieved within 90 s of the beginning of the bolus.ConclusionsGadofosveset injection is optimized for the lowest intravascular T1 time for 5–10 min duration MR angiography by bolus injection of 60–70 % of the total dose followed by slow infusion of the remainder of the total dose. This protocol achieves rapid and prolonged steady state intravascular concentrations of the GBCA that may be useful for prolonged image acquisition, such as required for navigator-based coronary MR angiography at 3 Tesla. Trial registrationClinicalTrials.gov identifier: NCT01130545NCT01130545, registered as of May 25, 2010.