Two macrocyclic gadolinium based contrast agents were utilized for this study: gadobutrol (Gadovist, Bayer Healthcare AG, Berlin, Germany) formulated at 1.0 molar (M) and gadoterate meglumine (Dotarem, Guerbet, France) formulated at 0.5 M. The r1 relaxivity of gadobutrol versus gadoterate meglumine is 5.0±0.3 vs. 3.5±0.2 L*mmol−1s−1 (in plasma, at 3 T and 37°C) [15] (link). To allow for a more equal comparison between the two different contrast agents in terms of bolus geometry the 1 M gadobutrol was diluted 1∶1 with normal saline (0.9% NaCl). Thus, contrast agents administered to the patients were equimolar on a per bodyweight basis (0.03 mmol/kg BW) and were administered in equivalent concentrations (0.5 M).
Gadoterate meglumine
Manufactured by Guerbet
Sourced in France, United Kingdom
Gadoterate meglumine is a gadolinium-based contrast agent used in magnetic resonance imaging (MRI) procedures. It is an injectable solution that enhances the visibility of internal body structures during MRI scans.
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Lab products found in correlation
Dotarem, by Guerbet (9 mentions)
Magnetom avanto, by Siemens (3 mentions)
Gadovist, by Bayer (2 mentions)
1.5t mri scanner, by Siemens (1 mentions)
18 channel cardiac coil, by Siemens (1 mentions)
Magnetom aera, by Siemens (1 mentions)
Ox063 trityl radical, by GE Healthcare (1 mentions)
1 13c pyruvic acid, by Cambridge Isotopes (1 mentions)
Hypersense polarizer, by Oxford Instruments (1 mentions)
Gadobutrol, by Bayer (1 mentions)
4 channel breast coil, by Siemens (1 mentions)
Spectris solaris, by Bayer (1 mentions)
Tim trio, by Siemens (1 mentions)
Circle cvi42, by Circle Cardiovascular Imaging (1 mentions)
3 tesla mri scanner, by Siemens (1 mentions)
Isite, by Philips (1 mentions)
Volumen, by Bracco (1 mentions)
Trityl radical ox063, by Oxford Instruments (1 mentions)
Hypersense, by Oxford Instruments (1 mentions)
Hypersense dnp polarizer, by Oxford Instruments (1 mentions)
23 protocols using gadoterate meglumine
1
Comparative Efficacy of Gadolinium Contrast Agents
2
Cardiac MRI Evaluation of Myocardial Infarction
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Cardiac magnetic resonance studies were performed using a commercial 1.5 T unit (Avanto‐Siemens, Erlangen, Germany). Breath‐hold steady‐state free‐precession cineMR images were acquired in cardiac vertical and horizontal long axis and short axis with full coverage of the ventricles. Area at risk (AAR) was assessed using black‐blood short tau inversion recovery T2‐weighted sequence (T2w imaging) acquired in cardiac long and short axis. After contrast administration, breath‐hold, two‐dimensional inversion recovery, segmented gradient‐echo T1‐weighted sequences were used to detect MVO and IS. An intravenous contrast agent dose of 0.1 mmol/kg gadolinium contrast agent (Gadoterate meglumine, Dotarem, Guerbet S.A., France) was used. The presence of MVO and late gadolinium enhancement (LGE) was assessed by early and late post‐contrast imaging acquired respectively 2–5 and 10–20 min following contrast administration. Inversion time was individually adapted to suppress the signal of normal remote myocardium (usual range, 220 to 350 ms). At 4 months follow‐up, the same CMR protocol was repeated except for T2‐weighted sequences.
3
Standardized Cardiac MRI Acquisition Protocol
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CMR images were acquired using 1.5T MRI scanner (Siemens Aera, Erlangen, Germany), an 18-channel cardiac coil and retrospective electrocardiographic (ECG) gating, using a standardised protocol, as previously published [24 (link)]. This included long (2- and 4-chamber) and short-axis cine images using a steady-state free precession end-expiratory breath-hold sequence (typical parameters: voxel size 1.90 × 1.52 × 8 mm, temporal resolution 48 ms, TR 2.76 and TE 1.15) and late gadolinium enhancement (LGE) images at the same slice positions following administration of a total of 0.15 mmol/kg of gadolinium-based contrast agent (Gadoterate meglumine, Dotarem, Guerbet LLC, France).
4
Cardiac MRI Protocol for Atrial Late Gadolinium Enhancement
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Cardiac magnetic resonance studies were conducted on a 1.5 T system (MAGNETOM AERA®, Siemens Medical Systems, Erlangen, Germany). The imaging protocol comprised cine SSFP imaging in a two-chamber view as well as in a stack of contiguous four-chamber views covering the entire LA. Black-blood T2-weighted imaging was acquired in a stack of contiguous four-chamber views covering the entire LA using a T2 SPAIR sequence performed before contrast injection. Atrial late gadolinium enhancement (LGE) imaging was initiated 20 min after the intravenous injection of 0.2 mmol/kg gadoterate meglumine (Guerbet, Aulnay-sous-bois, France). Imaging was acquired in trans-axial orientation at a mid-diastolic phase using a 3D, inversion-recovery-prepared, ECG-gated, respiration-navigated gradient-echo pulse sequence with fat-saturation.9 (link)
5
Hyperpolarization of [1-13C]pyruvic acid
6
Cardiac Magnetic Resonance Protocol for Tissue Characterization
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All participants underwent CMR at 1.5 Tesla at 4 sites (London, Avanto and Aera; Birmingham, Avanto; Sydney, Avanto; Siemens Healthcare, Erlangen, Germany) using a standard clinical protocol with LGE imaging using phase-sensitive inversion recovery. T1 mapping using a modified Look-Locker inversion recovery sequence and T2 mapping were performed pre–contrast bolus administration (0.1 mmol/kg body weight, Gadoterate meglumine, Dotarem, Guerbet SA, France) on basal left ventricular short-axis slices (Table I in the Data Supplement ). Post-T1 mapping was performed 15 minutes after contrast administration for ECV quantification. Contrast was not administered if estimated glomerular filtration rate <30 mL/min per 1.73 m2 or if the patient declined. Paired scans used identical sequences and magnets without upgrades, and phantom controls measured magnet stability for native T1 and T2 sequences.
7
Contrast-Enhanced MRI Imaging Protocols
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Imaging parameters according to clinical imaging protocols and scanners at each institution are described in Table 1 . All imaging series (conventional MR, DSC, and DW-images) were acquired with either a 1.5 or 3T superconducting system (General Electric® (GE) or Siemens®).
At Erasmus MC, Gadovist® (gadobutrol 1 mmol/ml, Bayer AG, Berlin, Germany) was used as contrast agent. A preload contrast dosage of 0.05 ml/kg was used and the remainder of a 15 ml Gadovist® bolus injection during DSC acquisition with a flowrate of 5 ml/s. At HMC, Dotarem® (Gadoterate meglumine 0.5 mmol/ml, Guerbet, Aulnay-sous-Bois, France) was used as a contrast agent. A preload dosage of 10 ml was used and a 20 ml Dotarem® bolus injection during DSC acquisition with a flowrate of 4 ml/s.
At Erasmus MC, Gadovist® (gadobutrol 1 mmol/ml, Bayer AG, Berlin, Germany) was used as contrast agent. A preload contrast dosage of 0.05 ml/kg was used and the remainder of a 15 ml Gadovist® bolus injection during DSC acquisition with a flowrate of 5 ml/s. At HMC, Dotarem® (Gadoterate meglumine 0.5 mmol/ml, Guerbet, Aulnay-sous-Bois, France) was used as a contrast agent. A preload dosage of 10 ml was used and a 20 ml Dotarem® bolus injection during DSC acquisition with a flowrate of 4 ml/s.
8
CMR-Based Multiparametric Myocardial Assessment
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All participants underwent CMR at 1.5 Tesla (Avanto (UK), Aera (Australia); Siemens Healthcare, Erlangen, Germany) using a standard protocol including LV cines in short axis (SAX), 4-chamber, 2-chamber and 3-chamber views. Native T1 mapping was performed precontrast on basal and mid left ventricular SAX slices using a shortened modified Look-Locker inversion recovery (ShMOLLI) sequence. 10 The resulting pixel by-pixel T1 color maps were displayed using a customized 12-bit lookup table, where normal myocardium was green, increasing T1 was red, and decreasing T1 was blue. Late Gadolinium enhancement (LGE) imaging was performed using phase sensitive inversion recovery (bolus administration of gadolinium 0.1 mmol/kg body weight, Gadoterate meglumine, Dotarem, Guerbet S.A., France)
9
Multiparametric MRI Breast Cancer Protocol
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All MR exams were performed with a 3 T MRI scanner (Tim Trio, Siemens, Erlangen, Germany) using a 4‐channel breast coil (InVivo, Orlando, FL) with the patient positioned in the center of the magnet in the prone position. Patients underwent a standardized multiparametric MRI protocol including T2‐weighted (T2w turbo spin echo) imaging, DWI (readout‐segmented echo planar imaging)1 and DCE T1‐weighted imaging (hybrid high spatial and temporal resolution protocol).30 The MRI sequence parameters for T2‐weighted and DCE‐MRI are summarized in online Table S1 and for DWI in Table S2. DWI was performed before the application of contrast agent with DCE‐MRI. For DCE‐MRI gadoterate meglumine (Dotarem, Guerbet, France) was injected intravenously as a bolus (0.1 mmol/kg body weight) by a power injector (Spectris Solaris, Medrad, Pittsburgh, PA) at 4 mL/s, followed by a 20‐mL saline flush. Contrast agent was injected 75 seconds after starting the first coronal T1‐weighted volumetric interpolated breath‐hold examination sequence. The total examination time was ~18:40 minutes.31
10
Comprehensive Cardiac MRI Protocol for Stress Perfusion Assessment
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Clinical perfusion-CMR studies were undertaken on either a 1.5 T (Siemens Avanto, Erlangen, Germany) or 3 T scanner (Siemens Skyra, Erlangen, Germany). Cardiac volumes and function were performed using standard CMR techniques as previously described by our group [21 (link)]. For stress perfusion, adenosine (140mcg/kg/min, increased up to a maximum of 210mcg/kg/min to achieve a satisfactory haemodynamic stress response) [18 (link)] was infused for 3–5 min. Patients underwent pulse, blood pressure and pulse oximetry monitoring at baseline and at 1-min intervals during adenosine infusion. Symptomatic response to adenosine was documented. During peak stress a bolus of gadolinium-based contrast (Gadoterate meglumine, Dotarem, Guerbet LLC, France) was injected (0.1 mmol/kg at 1.5 T and 0.075 mmol/kg at 3 T), followed by a 20 mL bolus of normal saline, at a rate of 5 mL/s and perfusion images were acquired using a saturation recovery gradient echo pulse sequence. Adenosine infusion was then discontinued and a complete short axis cine stack was performed before rest perfusion images were acquired following administration of a second bolus of gadolinium-based contrast agent (total dose 0.15 mmol/kg). LGE images in 3 long axis views and a complete short axis stack were acquired after a further delay of 5–10 min.
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