Blood-pool Agent Gadofosveset Research Articles

Leakage and water exchange characterization of gadofosveset in the myocardium

PurposeTo determine the compartmentalization of the blood pool agent gadofosveset and the effect of its transient binding to albumin on the quantification of steady-state fractional myocardial blood volume (fMBV). MethodsMyocardial vascular fraction measurements were simulated assuming the limiting cases (slow or fast) of two-compartment water exchange for different contrast agent injection concentrations, binding fractions, bound and free relaxivities, and true cardiac vascular fractions.fMBV was measured in five healthy volunteers (4 males, 1 female, average age 33) at 1.5T after administration of five injections of gadofosveset. The measurements in the volunteers were retrospectively compared to measurements of fMBV after three serial injections of the ultra-small, paramagnetic iron oxide (USPIO) blood pool agent ferumoxytol in an experimental animal. The true fMBV and exchange rate of water protons in both human and animal data sets was determined by chi square minimization. ResultsSimulations showed an error in the measurement of fMBV due to partial binding of gadofosveset of less than 30%. Measured fMBV values over-estimate simulation predictions, and approach cardiac extracellular volume (22%), which suggests that the intravascular assumption may not be appropriate for the myocardium, although it may apply to more distal perfusion beds. In comparison, fMBV measured with ferumoxytol (5%, with slow water proton exchange across vascular wall) agree with published values of myocardial vascular fraction. Further comparison between myocardium relaxation rates induced by gadofosveset and by other extracellular and intravascular contrast agents showed that gadofosveset behaves like an extracellular contrast agent. ConclusionsThe distribution of the volunteer data indicates that a three-compartment model, with slow water exchange of gadofosveset and water protons between the vascular and interstitial compartments, and fast water exchange between the interstitium and the myocytes, is appropriate. The ferumoxytol measurements indicate that this USPIO is an intravascular contrast agent that can be used to quantify myocardial blood volume, with the appropriate correction for water exchange using a two-compartment water exchange model.

Highly accelerated first‐pass contrast‐enhanced magnetic resonance angiography of the peripheral vasculature: Comparison of gadofosveset trisodium with gadopentetate dimeglumine contrast agents

To investigate the blood pool agent gadofosveset trisodium for first-pass, dynamic peripheral contrast-enhanced magnetic resonance angiography (pMRA), and compare the results with a conventional gadolinium contrast agent. A total of 16 patients were imaged at 1.5T using a prototype peripheral vascular coil with high SENSE acceleration. Five received gadopentetate dimeglumine ( approximately 0.25 mmol/kg), and 11 received gadofosveset trisodium (five standard-dose 0.03 mmol/kg, six high-dose 0.05 mmol/kg). Quantitative contrast-enhancement and qualitative image quality evaluation was compared between agents and doses. High-quality diagnostic images were uniformly obtained. The contrast ratio did not significantly differ between gadopentetate dimeglumine and high-dose gadofosveset trisodium, both of which were greater than standard-dose gadofosveset trisodium. High-dose gadofosveset trisodium was equivalent to gadopentetate dimeglumine in image quality and subjective vessel-to-background ratio, but significantly better for depicting small muscular arteries. Standard-dose gadofosveset trisodium showed equivalent image quality and small artery depiction with a slight but significant decrease in vessel-to-background ratio as compared to gadopentatate dimeglumine. Both gadofosveset trisodium doses trended toward more venous enhancement, but this was not a diagnostic problem. First-pass peripheral CE-MRA using gadofosveset trisodium is feasible, yielding image quality comparable to double to triple-dose gadopentetate dimeglumine. Increasing the gadofosveset trisodium dose to 0.05 mmol/kg yields further improvements.

Human brain tumor imaging with a protein-binding MR contrast agent: initial experience

Gadofosveset is a Gd-based protein-binding blood pool agent with increased relaxivities and blood half-life compared with conventional Gd-based contrast agents (GBCAs). No experience exists about the use of gadofosveset as an extracellular agent. In this report we present the first clinical experience with gadofosveset in enhancing intracranial tumors. Ten patients with different intracranial tumors were examined with a standard dose (0.03 mmol/kg) of gadofosveset compared with a standard dose (0.1 mmol/kg) of conventional GBCA. As a result of its significantly higher relaxivity, gadofosveset could, despite its low dose, achieve a sufficient contrast enhancement. The visual rating of the intensity of enhancement and the contrast to noise ratios were comparable to conventional agents. The detection and delineation of more complex lesions was rated equal. In one nonenhancing low grade astrocytoma an enhancing nodule became visible only 5 h after gadofosvesest injection. As shown in this initial report, contrast-enhanced intracranial tumor imaging is possible with the protein-binding blood pool agent gadofosveset. The agent gives a significant tumor contrast in early postcontrast imaging comparable with conventional agents. As a result of its unique longer lasting contrast, the use of gadofosveset might enable a new approach to imaging mild or nonenhancing tumors.

High spatial resolution magnetic resonance imaging of experimental cerebral venous thrombosis with a blood pool contrast agent

Purpose The purpose of this study was to investigate the feasibility of clot visualization in small sinus and cortical veins with contrast enhanced MRA in a cerebral venous thrombosis animal model using a blood pool contrast agent, Gadofosveset, and high spatial resolution imaging. Material and methods For induction of cerebral venous thrombosis a recently developed combined interventional and microsurgical model was used. Cerebral sinus and cortical vein thrombosis was induced in six pigs. Two further pigs died during the procedure. Standard structural, time-of-flight- and phase contrast-angiograms were followed by fast time resolved high resolution 3D MRA (4D MRA) and subsequent high spatial resolution 3D MRA in the equilibrium phase with and without addition of parallel imaging. Visualization of the clots using the different sequences was subjectively compared and contrast-to-noise ratio (CNR) was assessed. Results In the remaining six animals the procedure and MR-imaging protocol including administration of Gadofosveset was successfully completed. The 3D high resolution MRA in the equilibrium phase without the addition of parallel imaging was superior to all the other applied MR measurement techniques in terms of visualization of the clots. Only applying this sequence bridging vein thromboses were also seen as a small filling defect with a high CNR of >18. Conclusion Only the non-accelerated high spatial resolution 3D MRA in the equilibrium in conjunction with the blood pool agent Gadofosveset allows for high-contrast visualization of very small clots in the cerebral sinus and cortical veins. Statement clinical impact Detection of cortical vein thrombosis is of high clinical impact. Conventional MRI sequences often fail to visualize the clot. We could demonstrate that, in contrast to conventional sequences, with high spatial resolution 3D MRA in the equilibrium in conjunction with the blood pool agent Gadofosveset very small clots in the cerebral sinus and cortical veins could be successfully visualized. We think that with the presented approach cortical vein thrombosis might also be sufficiently visualized in patients.

Peripheral vascular imaging with a blood pool contrast agent: imaging strategies and influence on patient management

Magnetic resonance angiography (MRA) with the blood pool agent gadofosveset trisodium (Vasovist®, Bayer Schering Pharma AG, Berlin, Germany) is a promising new, non-invasive imaging modality for the detection and characterisation of peripheral vascular disease. It offers for the first time the ability to expand the imaging window far beyond the first arterial bolus passage and allows for the acquisition of very high spatial resolution data during the so-called steady state (blood pool or equilibrium phase). Furthermore, information about the venous system is available with a blood pool agent without the need of multiple injections. In this article imaging strategies for peripheral MRA with gadofosveset trisodium are discussed. We describe the advantages of high resolution steady state imaging and provide recent clinical results of this new imaging tool which shows improved diagnostic accuracy of steady-state imaging compared to first-pass imaging and DSA as the reference standard and impact on patient management.

Dynamic magnetic resonance angiography of the arteries of the hand. A comparison between an extracellular and an intravascular contrast agent

The purpose of this study was to compare the image quality of the intravascular contrast agent gadofosveset with the extracellular contrast agent gadoterate meglumine in time-resolved three-dimensional magnetic resonance (MR) angiography of the human arteries of the hand. The value of cuff compression technique for suppression of venous enhancement for both contrast agents was also investigated. Three-dimensional MR angiograms of both hands of 11 healthy volunteers were acquired for each contrast agent at 1.5-T, while subsystolic cuff compression was applied at one side. Quantitative and qualitative evaluation were performed and analyzed with Student's t-test. Visualization of vessels was superior in the images acquired with gadofosveset, especially in the late phases. Quantitative and qualitative evaluation showed significantly higher values for gadofosveset. The cuff compression at the lower arm proved to be an effective method to enhance arterial vessels. In conclusion the blood pool agent gadofosveset is superior for the dynamic imaging of the vessels of the hand when compared with the extracellular contrast agent gadoterate meglumine. To fully utilize the advantages of intravascular contrast agents, venous overlay has to be delayed or reduced, which can be achieved effectively by subsystolic lower arm cuff compression.

Cardiac cine MRI: Comparison of 1.5 T, non-enhanced 3.0 T and blood pool enhanced 3.0 T imaging

Introduction Cardiac cine imaging using balanced steady state free precession sequences (bSSFP) suffers from artefacts at 3.0 T. We compared bSSFP cardiac cine imaging at 1.5 T with gradient echo imaging at 3.0 T with and without a blood pool contrast agent. Materials and methods Eleven patients referred for cardiac cine imaging underwent imaging at 1.5 T and 3.0 T. At 3.0 T images were acquired before and after administration of 0.03 mmol/kg gadofosveset. Blood pool signal-to-noise ratio (SNR), temporal variations in SNR, ejection fraction and myocardial mass were compared. Subjective image quality was scored on a four-point scale. Results Blood pool SNR increased with more than 75% at 3.0 T compared to 1.5 T ( p < 0.001); after contrast administration at 3.0 T SNR increased with 139% ( p < 0.001). However, variations in blood pool SNR at 3.0 T were nearly three times as high versus those at 1.5 T in the absence of contrast medium ( p < 0.001); after contrast administration this was reduced to approximately a factor 1.4 ( p = 0.21). Saturation artefacts led to significant overestimation of ejection fraction in the absence of contrast administration (1.5 T: 44.7 ± 3.1 vs. 3.0 T: 50.7 ± 4.2 [ p = 0.04] vs. 3.0 T post contrast: 43.4 ± 2.9 [ p = 0.55]). Subjective image quality was highest for 1.5 T (2.8 ± 0.3), and lowest for non-enhanced 3.0 T (1.7 ± 0.6; p = 0.006). Conclusions GRE cardiac cine imaging at 3.0 T after injection of the blood pool agent gadofosveset leads to improved objective and subjective cardiac cine image quality at 3.0 T and to the same conclusions regarding cardiac ejection fraction compared to bSSFP imaging at 1.5 T.