Impact of concentration and dilution of three macrocyclic gadolinium-based contrast agents on MRI signal intensity at 1.5T and 3T and different pulse sequences: results of a phantom study in human plasma.

BACKGROUND: Many factors influence the increase in signal intensity (SI) provided by magnetic resonance imaging (MRI) contrast media. PURPOSE: To assess the impact of different gadolinium concentrations and dilutions of three macrocyclic gadolinium-based contrast agents (GBCA) on SI. MATERIAL AND METHODS: This phantom study investigated gadobutrol, gadoteridol, and gadoterate in human plasma of a healthy donor pool at 37 °C. Different molar concentrations served to mimic conditions typically relevant for steady-state imaging; different dilutions served to mimic influence on first-pass bolus imaging. For SI measurement at 1.5T and 3T, we used two Magnetom Scanners (Siemens), applying the T1-weighted sequences Flash 2D/3D and VIBE. Regions of interest were placed on the central slice of the test vials. RESULTS: In the concentration series, gadobutrol showed the highest SI of all three GBCAs up to 2 mM, followed by gadoteridol and gadoterate. No major differences were seen between 1.5T and 3T. In the dilution series, gadobutrol showed the highest SI of all three GBCAs up to 10 mL/L. The highest effect was recorded with Flash 3D and VIBE at 3T. CONCLUSION: SIs measured in phantoms using three macrocyclic GBCAs strongly depend on their relaxivity and on the local concentration. The latter can be influenced-when comparing dilutions-by their initial concentration in their formulation. Furthermore, the pulse sequences and the chosen parameters have essential influence. At steady-state concentrations (≤2 mM) and first-pass bolus dilutions (up to 10 ml/L), gadobutrol showed highest SIs, followed by gadoterate and gadoteridol.

Comparison of the Relaxivities of Macrocyclic Gadolinium-Based Contrast Agents in Human Plasma at 1.5, 3, and 7 T, and Blood at 3 T.

PURPOSE: The relaxivities of 3 macrocyclic gadolinium-based contrast agents (GBCAs) were determined in human plasma and blood under standardized and clinically relevant laboratory conditions. METHODS: The T1 relaxivity, r1, was determined in human plasma at 1.5, 3, and 7 T, and in human blood at 3 T at 37°C in phantoms containing 4 different concentrations of the macrocyclic GBCAs gadobutrol, gadoteridol, and gadoterate. An inversion recovery turbo spin echo sequence was used to generate images with several inversion times. The T1-times were obtained by fitting the signal intensities to the signal equation. r1 was obtained by a 1/y-weighted regression of the T1-rates over the concentration of the GBCAs. RESULTS: For gadobutrol, the obtained r1 [L/(mmol·s)] in human plasma at 1.5 T, 3 T, and 7 T, and in human blood at 3 T was 4.78 ± 0.12, 4.97 ± 0.59, 3.83 ± 0.24, and 3.47 ± 0.16. For gadoteridol, r1 was 3.80 ± 0.10, 3.28 ± 0.09, 3.21 ± 0.07, and 2.61 ± 0.16, and for gadoterate, 3.32 ± 0.13, 3.00 ± 0.13, 2.84 ± 0.09, and 2.72 ± 0.17. CONCLUSIONS: The relaxivity of gadobutrol is significantly higher than that of gadoteridol and gadoterate at all magnetic field strengths and in plasma as well as in blood, whereas that of gadoteridol was higher than gadoterate only in plasma at 1.5 and 7 T. This is in accordance with results from 3 previous studies obtained in different media.

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.

Thoracic and abdominal MRA with gadofosveset: influence of injection rate on vessel signal and image quality.

The purpose of this study was to investigate the influence of different injection rates on the maximum signal intensity and the arterio-venous transit time of dynamic gadofosveset-enhanced first pass MR angiography (MRA). Twenty-one healthy male volunteers were examined with a time-resolved echo-shared MRA at 1.5 T. The volunteers were assigned into three groups using injection rates of either 1, 2 or 4 ml/s. The maximal signal enhancement and peak signal-to-noise ratio in the pulmonary trunk, the aortic arch, the abdominal aorta as well as both kidneys and lung parenchyma were analyzed. The arterio-venous transit time was determined. The time between maximal enhancement of the pulmonary trunk and the aortic arch was higher with the slow injection rate of 1 ml/s, while there were no differences in the time between maximal enhancement of the aortic arch and the abdominal aorta above or below the origin of the renal veins with all three injection rates. With the slow injection protocol of 1 ml/s a longer purely arterial phase of 10.5 s was achieved compared to 7.7 s with higher injection rates (p = 0.045). The time between maximal aortic signal intensity and maximal renal enhancement was equal for all injection protocols.

Technical requirements, biophysical considerations and protocol optimization with magnetic resonance angiography using blood-pool agents.

In order to maximize the potential benefits of contrast-enhanced magnetic resonance angiography, careful attention must be paid to the choice of hardware, data acquisition and processing, and to the choice of contrast agent. Typically, contrast-enhanced magnetic resonance angiography uses parallel-imaging techniques, which shorten the acquisition time, enhance spatial resolution and reduce artefacts. The timing of data acquisition is crucial for maximal enhancement of the arteries: for optimal arterial depiction, the centre of k-space should be acquired at the time of peak concentration of contrast agent in the arterial bed being investigated, and a number of k-space acquisition techniques are available to achieve this. SENSE or GRAPPA techniques can be used to facilitate parallel-imaging reconstruction of either the image data or k-space data, respectively. Gadolinium contrast agents shorten the proton relaxation times (most importantly T1) of blood, thereby increasing the signal-to-noise ratio and enhancing differentiation between blood vessels and other tissues. The blood-pool (intravascular) contrast agent gadofosveset trisodium (Vasovist, Bayer Schering Pharma AG, Berlin, Germany) is reversibly protein-bound in human plasma. This results in a marked increase in relaxivity, and hence a strong T1 shortening effect compared with other gadolinium-based contrast agents. Furthermore, the blood retention time of gadofosveset trisodium is substantially prolonged compared with conventional contrast agents. As a result, gadofosveset trisodium permits both first-pass and steady-state imaging.

Effects of injection rate and dose on image quality in time-resolved magnetic resonance angiography (MRA) by using 1.0M contrast agents.

In time-resolved MRA (TR MRA), injection parameters and contrast agent (CA) dose are important factors influencing image quality. In this study, three different injection schemes with different CA volumes were evaluated in 12 healthy volunteers. Injection rates between 0.2 and 0.8 ml/s were evaluated with CA volumes of 10 and 20 ml. To measure circulatory parameters, cine cardiac MRI was performed before each exam. Spatial resolution could be reduced to 2 x 1.4 x 2 mm3, temporal resolution was 2.25 s/frame. To exclude signal saturation at high CA concentrations, a phantom with fixed CA concentrations was placed in the field of view. SNR was measured, and the area under the curve of the arterial signal of the different injection schemes was calculated. Results showed the largest diagnostic window at a relatively slow injection rate of 0.4 ml/s and a CA volume of 10 ml. Circulatory parameters have an important impact on CA arrival, so delay times have to be set depending on these parameters.

Initial imaging recommendations for Vasovist angiography.

Vasovist is a newly developed blood pool contrast agent for MR angiogiography (MRA). It consists of a low molecular weight molecule, chelated to Gadolinium, that strongly binds to plasma proteins, thus increasing its relaxivity and retention time in the vascular system. Due to its high efficiency, a smaller dose compared to existing Extracellular Fluid Contrast Agents is sufficient for diagnostic purposes, resulting in a lower injection volume. With appropriate adjustments of standard extracellular contrast injection protocols, a dynamic phase MRA can be achieved using routine MRA parameters. For extended phase imaging, ('steady-state') starting approximately 3 to 5 min post injection, repetition time (TR) and flip angle may be adjusted for optimization of intravascular signal. Preliminary technical recommendations for the optimization of contrast-enhanced MRA with Vasovist can be deducted from current clinical trial experience in various vessel beds.

Comparison of magnetic properties of MRI contrast media solutions at different magnetic field strengths.

RATIONALE AND OBJECTIVES: To characterize and compare commercially available contrast media (CM) for magnetic resonance imaging (MRI) in terms of their relaxivity at magnetic field strengths ranging from 0.47 T to 4.7 T at physiological temperatures in water and in plasma. Relaxivities also were quantified in whole blood at 1.5 T. METHODS: Relaxivities of MRI-CM were determined by nuclear magnetic resonance (NMR) spectroscopy at 0.47 T and MRI phantom measurements at 1.5 T, 3 T, and 4.7 T, respectively. Both longitudinal (T1) and transverse relaxation times (T2) were measured by appropriate spin-echo sequences. Nuclear magnetic resonance dispersion (NMRD) profiles were also determined for all agents in water and in plasma. RESULTS: Significant dependencies of relaxivities on the field strength and solvents were quantified. Protein binding leads to both increased field strength and solvent dependencies and hence to significantly altered T1 relaxivity values at higher magnetic field strengths. CONCLUSIONS: Awareness of the field strength and solvent associated with relaxivity data is crucial for the comparison and evaluation of relaxivity values. Data observed at 0.47 T can thus be misleading and should be replaced by relaxivities measured at 1.5 T and at 3 T in plasma at physiological temperature.