Gadobenate dimeglumine

The goal in the development of RAPID was to automatically perform a time-critical assessment of potentially salvageable tissue in acute stroke patients. These data allow the physician to avoid potentially harmful reperfusion therapies in stroke patients with either a malignant profile or little salvageable tissue (1 (link)), without the need for a skilled operator to perform PWI and DWI analysis and quantification. Therefore, the system's performance and reliability in predicting mismatch was evaluated and compared to the analysis of the same data by an experienced stroke neurologist or neuroradiologist.
For testing and evaluation purposes, data from the DEFUSE multi-center (7 sites) trial (1) were analyzed. In this trial, single-shot GRE-EPI DSC-MRI perfusion MRI data were acquired at 1.5 T whole-body scanners. Depending on make and model, the scan parameters were as follows: TR = 1.4 - 2.0 s, TE = 40 - 60 ms, matrix 128², field-of-view 24 cm, 12 - 16 slices (5 - 7 mm thick separated by gaps of 0 - 2 mm) to cover the supertentorial brain, and 40 - 80 time points. A single-dose bolus (0.1 mmol/kg) injection of a gadolinium-based paramagnetic tracer (gadopentetate dimeglumine or gadobenate dimeglumine) was administered typically 10 - 15 s after the start of the dynamic scan using a MR-compatible power injector followed by 20 - 25 ml of saline flush at the same flow rate.
In addition to the perfusion MRI data, diffusion-weighted MRI data were also obtained as part of the DEFUSE trial. Specifically, single-shot diffusion-weighted spin-echo EPI scans were acquired with the following scan parameters: TR = 4 - 6 s, TE = 60 - 80 ms, matrix 128², field-of-view 24 cm, and 12 - 24 slices (5 mm thick separated by gaps of 0 - 2 mm). Diffusion-weighted images were acquired with encoding gradients played out separately along the three principal axes at a b-value of 1000 s/mm² plus one scan where the diffusion-encoding gradients were turned off (b = 0 image), resulting in a total of 4 different diffusion weightings. Thereafter, the three directionally-dependent diffusion-weighted images were combined to generate an isotropic diffusion-weighted image (b = 1000 image).
The lesion volumes identified by RAPID were compared to those identified by a human reader in 63 out of 74 cases, where both DWI and PWI were available and of good diagnostic quality. PWI maps generated by RAPID (that included corrections for motion and different slice times in interleaved-slice EPI acquisitions) were used for both the manual and the automated T_max lesion segmentation. Attention was paid by the human reader to check if the AIF used in PWI processing was selected appropriately. Additionally, both methods used identical segmentation criteria (ADC and T_max thresholds). RAPID and the human reader used mismatch criteria that were based on the original DEFUSE study (1 (link)). A mismatch was considered positive if the difference between the PWI and DWI lesion volume was at least 10 ml and the PWI/DWI volume ratio was at least 1.2. The agreement between diffusion-perfusion-mismatch identified by the human reader and RAPID was analyzed by true positive and false positive rates. Here, the assessment of mismatch by the human reader was considered as ground truth (the ‘gold standard’). Finally, the inter-reader agreement between the human reader and the RAPID was assessed by Cohen's kappa value.

Time-resolved CE-MRA studies using the CAPR sequence were performed in human subject volunteers at 1.5T and 3.0T (GE Signa, Version 12.0 Excite) according to a protocol approved by our institutional review board. The typical scan parameters were: 3D spoiled gradient echo (GRE) sequence using TR/TE of 3.8/1.2 msec; flip angle 30°; BW ±62.5 kHz; sampling matrix 256 (S/I, frequency), 48–96 (A/P, phase), 32–64 (R/L slice); FOV of 25 cm (S/I and A/P) and 12–24 cm (R/L); and typical 2 min. in duration. It was useful to restrict the FOV along both the readout and the slice select directions precisely to the anatomy of interest, as facilitated by the 3DFT nature of the sequence. At both field strengths a similar eight-element head coil (MRI Devices, Waukesha, WI) was used. For all studies, 20 ml of gadobenate dimeglumine agent (MultiHance; Bracco Diagnostics, Princeton, NJ) was administered using an electronic injector into the right antecubital vein at 3 ml/sec followed by 20 ml of saline at 2 ml/sec. The last contrast-free frame was taken as the mask for subtraction of any background signal. 2D SENSE accelerations were typically performed using R_Y = 2 – 2.67 and R_Z = 2, yielding net acceleration factors R = 4 – 5.33. SENSE unfolding coefficients were obtained using a full resolution calibration scan consisting of a sagittal GRE pulse sequence with TR/TE 10/3 ms, flip angle = 10°, NEX = 1, and a bandwidth of ±31.25 kHz acquired prior to contrast injection and scaled by the sum of squares composite image of all coils. Acquisition parameters of in vivo studies are also given in Table 1.

Twenty-nine patients referred for clinical CMR (58±15 y, 19 male) were recruited. Informed consent was obtained from all participants and the imaging protocol was approved by our institutional review board. All patients were scanned using a 1.5T Philips Achieva (Philips Healthcare, Best, The Netherlands) scanner with a 32-channel cardiac phased array receiver coil. Each patient received an injection of 0.1 mmol/kg of gadobenate dimeglumine (MultiHance; Bracco Diagnostic Inc., Princeton, NJ). T₁ mapping was performed using the MOLLI sequence (12 (link)) before and after contrast administration. The 5-(3 (link))-3 MOLLI scheme was used for pre-contrast T₁ mapping while the 4-(1 (link))-3-(1 (link))-2 MOLLI scheme was used for post contrast T₁ mapping (29 (link)). Both sequences used a balanced-SSFP readout (TR/TE=3.1/1.5ms, FOV=360×337 mm², acquisition matrix=188×135, voxel size=1.9×2.5 mm², slice thickness=8 mm, number of phase-encoding lines=70, linear ordering, 10 linear ramp-up pulses, SENSE factor=2, flip angle=35/70°, bandwidth=1085Hz/pixel). T₁ scans have been acquired in the short axis views using either 1 or 3 slices for the first 20 patients. A single slice has been acquired in the four chamber orientation for the last nine patients. Three T₁ scans were acquired for each patient: one before contrast injection, and two post-contrast scans at 15±5 min and 31±6 min after contrast injection, respectively. Note that post-contrast T₁ mapping could not be performed in all patients.