Gadobenate dimeglumine

Patients were scanned supine on a 3T whole-body MR scanner (Discovery MR750, GE Healthcare, Milwaukee, WI) and 1.5T whole-body MR scanner (GE Signa EXCITE HDxt, GE Healthcare, Waukesha, WI; Philips Achieva) with an eight-channel phased-array coil centered over the liver. Precontrast sequences included breath-hold coronal fast imaging employing steady-state acquisition (FIESTA), breath-hold coronal single-shot fast spin echo (SSFSE), respiratory-triggered axial T2-weighted fast spin echo (FSE), breath-hold two-dimensional dual-echo T1-weighted gradient-recalled-echo images at nominal opposed/in phase echo times for 1.5 T and 3 T, and respiratory-triggered axial diffusion-weighted spin-echo echo-planar imaging with 2 b values (b = 0 and 800 sec/mm²). Afterwards, breath-hold 3D T1W gradient-recalled-echo imaging (liver acquisition with volume acceleration) was performed before and at multiple time points dynamically after injection of gadobenate dimeglumine (Bracco), gadopentetate dimeglumine (Bayer), or gadoxetate disodium (Bayer). A dual arterial phase (AP) was initiated 15–20 seconds after the contrast media arrived at the distal thoracic aorta using bolus triggering, a portal venous phase (PVP) was acquired at 1 minute after contrast injection, and a delayed phase (DP)/transitional phase (TP) was acquired at 3 minutes. Twelve MRIs included delayed hepatobiliary phase imaging.

All of the MRI examinations were performed with the patient placed in a prone position on a 1.5-T unit (Sonata Symphony class, Siemens Healthineers, Erlangen, Germany) with gradients up to 40-mT/m, using bilateral four-element dedicated phased-array coils.
The image acquisition started with a triplane scout view, followed by a series of bilateral axial sequences: (A) T2-weighted short-tau inversion recovery (inversion time 150 ms, flip angle 150°); (B) fat-saturated echo-planar diffusion-weighted imaging (b-values 0 and 750 s/mm²); (C) dynamic contrast-enhanced T1-weighted three-dimensional fast low-angle shot spoiled gradient-echo, acquired once before and four times after the intravenous injection of a 0.1 mmol/kg dose of a gadolinium-based contrast agent (gadobenate dimeglumine, Bracco Imaging, Milan, Italy, or gadobutrol, Bayer Healthcare, Berlin Germany), with a temporal resolution of 119 s. Other details on the acquisition parameters are listed in Table 1.

A 1.5 T whole-body scanner (Philips) with an ECG triggering device was used for CMR imaging. Respiratory bellows were placed on the patient’s abdomen throughout the imaging process. After the acquisition of localisation images, continuous short-axis cine images of the left ventricle were obtained using steady state free precession sequence at end-expiration.
Ventricular volumes and left- and right-ventricular ejection fractions were calculated using four-chamber and short-axis slice summation.
Images depicting late gadolinium enhancement (LGE) were acquired approximately 15 min after administering 0.1 mmol/kg of gadobenate dimeglumine (Bracco Diagnostics Inc., Princeton, NJ, USA) at an injection rate of 2 mL per second. The presence of LGE was evaluated using segmented inversion recovery prepared for true fast imaging. The images were visually analysed for the presence and extent of LGE. Two radiologists were available for image interpretation, and a single radiologist independently reviewed each set of CMR images. The visual scoring method was based on the 17-segment model. The percentage of the myocardium with LGE was calculated by counting the number of segments with LGE and dividing by 17.

Images were acquired using two 3T systems (Magnetom Skyra, Siemens Healthcare and Achieva, Philips Medical System). The imaging protocol included at least axial spin-echo T1-weighted imaging, axial fluid-attenuated inversion recovery imaging (FLAIR), followed by DSC-MRI data and contrast-enhanced gradient-echo 3D T1-weighted imaging (CE-T1WI).
DSC-MRI was acquired with a gradient-echo echoplanar imaging technique during the first pass of a standard bolus of gadolinium contrast without pre-load bolus. The imaging parameters were as follows: Magnetom: TR 1710 ms, TE 20 ms, slice 4 mm, flip angle 90°; Achieva: TR 1657 ms, TE 40 ms, slice thickness 4 mm, flip angle 75°. During 45 consecutive echoplanar imaging scans lasting 1 minute 30 seconds, an intravenous bolus injection of 0.2 ml/kg gadolinium chelate (Gadobenate dimeglumine, Multihance®, Bracco, Italy or Gadoteric acid, Dotarem®, Guerbet, France) was administered at a flow rate of 5 ml/s followed by a 20 ml saline flush.
3D CE-T1WI data were acquired with the following parameters for Magnetom: TR 1670 ms, TE 2.30 ms, slice thickness 1 mm, flip angle 8° and Achieva: TR 9.89 ms, TE 4.60 ms, slice 1 mm, flip angle 8°. FLAIR data were acquired with the following parameters for both machines: TR 8000 ms, TE 100 ms, slice thickness 3 mm.

Protected N^α-Fmoc-amino acid derivatives, coupling reagents and Rink amide MBHA (4-methylbenzhydrylamine) resin are commercially available from Calbiochem-Novabiochem (Laufelfingen, Switzerland). All other chemicals are commercially available from Merck (Milan, Italy), Fluka (Bucks, Switzerland), or LabScan (Stillorgan, Dublin, Ireland) and unless stated otherwise, they were used as delivered. [Gd(BOPTA)]²⁻ (Gadobenate dimeglumine, MultiHance) was kindly provided by Bracco Imaging S.p.A. [Gd(AAZTA)]⁻ was synthesized as reported previously [26 (link)]. Peptide solutions were prepared by weight using double distilled water.
To promote the complexation in [Gd(DTPA)]²⁻, Diethylenetriaminepentaacetic acid (DTPA) (20 mg, 0.05 mmol) was dissolved in 2 mL of pure water in the presence of a molar excess of GdCl₃·6H₂O. The pH of the solution was corrected to 6 with NaOH 0.1 M and the reaction was maintained under stirring at room temperature for 1h. Then, the pH was increased to 9.5 to promote the precipitation of unreacted Gd³⁺ that was filtered out, and the pH of the solution was corrected to 7 with diluted HCl (0.1 M).