Automated workflow for volumetric assessment of signal intensity ratio on T1-weighted MR images after multiple gadolinium administrations.

Purpose: Repeated injections of linear gadolinium-based contrast agent (GBCA) have shown correlations with increased signal intensities (SI) on unenhanced T1-weighted (T1w) images. Assessment is usually performed manually on a single slice and the SI as an average of a freehand region-of-interest is reported. We aim to develop a fully automated software that segments and computes SI ratio of dentate nucleus (DN) to pons (DN/P) and globus pallidus (GP) to thalamus (GP/T) for the assessment of gadolinium presence in the brain after a serial GBCA administrations. Approach: All patients ( N = 113 ) underwent at least eight GBCA enhanced scans. The modal SI in the DN, GP, pons, and thalamus were measured volumetrically on unenhanced T1w images and corrected based on the reference protocol (measurement 1) and compared to the SI-uncorrected-modal-volume (measurement 2), SI-corrected-mean-volume (measurement 3), as well as SI-corrected-modal-single slice (measurement 4) approaches. Results: Automatic processing worked on all 2119 studies (1150 at 1.5 T and 969 at 3 T). DN/P were 1.085 ± 0.048 (1.5 T) and 0.979 ± 0.061 (3 T). GP/T were 1.084 ± 0.039 (1.5 T) and 1.069 ± 0.042 (3 T). Modal DN/P ratios from volumetric assessment at 1.5 T failed to show a statistical difference with or without SI corrections ( p = 0.71 ). All other t -tests demonstrated significant differences (measurement 2, 3, 4 compared to 1, p < 0.001 ). Conclusion: The fully automatic method is an effective powerful tool to streamline the analysis of SI ratios in the deep brain tissues. Divergent SI ratios using different approaches reinforces the need to standardize the measurement for the research in this field.

Efficacy and safety of gadobutrol-enhanced MRA of the renal arteries: Results from GRAMS (Gadobutrol-enhanced renal artery MRA study), a prospective, intraindividual multicenter phase 3 blinded study.

PURPOSE: To compare the performance of magnetic resonance angiography (MRA) with 1M gadobutrol, a high relaxivity macrocyclic contrast agent, to 2D time-of-flight MRA (ToF-MRA) using computed tomographic angiography (CTA) as the standard of reference. Primary objectives were evaluation for superiority of structural delineation and noninferiority for detection and exclusion of clinically significant disease. MATERIALS AND METHODS: In all, 315 subjects underwent unenhanced and contrast-enhanced MRA with 1M gadobutrol (CE-MRA) and were scanned with 1.5T MRI equipped with an at least 6-element body coil. Evaluations were based on both centralized blinded read (BR) performed by six readers as well as investigator site interpretations for the 292 subjects who completed the study. Quantitative evaluations including percent stenosis and normal vessel measurements were also performed. Secondary endpoints included identification of accessory renal arteries, diagnosis of fibromuscular dysplasia (FMD), diagnostic confidence, and need for additional imaging. RESULTS: A total of 292 patients suspected of renal artery disease completed the study. CE-MRA demonstrated statistically significant improvement in assessability of vascular segments compared to ToF: 95.9% vs. 77.6% (P < 0.0001). In the BR, the sensitivity and specificity of CE-MRA were noninferior to ToF-MRA (53.4% vs. 46.6% and 95.1% vs. 85.7%, respectively). There was less error in the CE-MRA stenosis measurements (0.15 mm gadobutrol vs. 0.41 mm ToF, P < 0.05). FMD was correctly diagnosed more frequently, 10% more accessory renal arteries were identified (P < 0.01), diagnostic confidence increased (P < 0.01), and fewer additional imaging studies were recommended (P < 0.01). CONCLUSION: Gadobutrol-enhanced MRA of the renal arteries has superior visualization, more accurate vessel measurements, and may serve as a CTA alternative without any ionizing radiation. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:572-581.

What Evidence Is There That Gadobutrol Causes Increasing Signal Intensity within the Dentate Nucleus and Globus Pallidus on Unenhanced T1W MRI in Patients with RRMS?

KEY POINTS : The study by Stojanov et al does not convincingly support the conclusion that gadobutrol causes higher T1 enhancement in brain on unenhanced MRI. The study by Stojanov et al does not rule out confounding factors . The study by Stojanov et al has limitations in study design.

Safety and Efficacy of Gadobutrol for Contrast-enhanced Magnetic Resonance Imaging of the Central Nervous System: Results from a Multicenter, Double-blind, Randomized, Comparator Study.

PURPOSE: Contrast-enhanced magnetic resonance imaging (MRI) of the central nervous system (CNS) with gadolinium-based contrast agents (GBCAs) is standard of care for CNS imaging and diagnosis because of the visualization of lesions that cause blood-brain barrier breakdown. Gadobutrol is a macrocyclic GBCA with high concentration and high relaxivity. The objective of this study was to compare the safety and efficacy of gadobutrol 1.0 M vs unenhanced imaging and vs the approved macrocyclic agent gadoteridol 0.5 M at a dose of 0.1 mmol/kg bodyweight. MATERIALS AND METHODS: Prospective, multicenter, double-blind, crossover trial in patients who underwent unenhanced MRI followed by enhanced imaging with gadobutrol or gadoteridol. Three blinded readers assessed the magnetic resonance images. The primary efficacy variables included number of lesions detected, degree of lesion contrast-enhancement, lesion border delineation, and lesion internal morphology. RESULTS: Of the 402 treated patients, 390 patients received study drugs. Lesion contrast-enhancement, lesion border delineation, and lesion internal morphology were superior for combined unenhanced/gadobutrol-enhanced imaging vs unenhanced imaging (P < 0.0001 for all). Compared with gadoteridol, gadobutrol was non-inferior for all primary variables and superior for lesion contrast-enhancement, as well as sensitivity and accuracy for detection of malignant disease. The percentage of patients with at least one drug-related adverse event was similar for gadobutrol (10.0%) and gadoteridol (9.7%). CONCLUSION: Gadobutrol is an effective and well-tolerated macrocyclic contrast agent for MRI of the CNS. Gadobutrol demonstrates greater contrast-enhancement and improved sensitivity and accuracy for detection of malignant disease than gadoteridol, likely because of its higher relaxivity.

Phase 3 efficacy and safety trial of gadobutrol, a 1.0 molar macrocyclic MR imaging contrast agent, in patients referred for contrast-enhanced MR imaging of the central nervous system.

PURPOSE: Gadobutrol is a 1.0 M macrocyclic magnetic resonance imaging (MRI) contrast agent. A study was performed to evaluate the efficacy and safety of gadobutrol-enhanced versus unenhanced imaging for central nervous system (CNS) lesion visualization and detection. MATERIALS AND METHODS: An international, multicenter, open-label, Phase III clinical trial. Patients underwent unenhanced and gadobutrol 1.0 M-enhanced (0.1 mmol/kg BW) MR imaging using a standardized protocol. Unenhanced and combined unenhanced/gadobutrol-enhanced images were scored by three independent, blinded readers for degree of lesion enhancement, border delineation, internal morphology, and total number of lesions detected (primary efficacy variables). Exact match of the MR diagnoses with the final clinical diagnosis, detection of malignant CNS lesions, and confidence in diagnosis were secondary efficacy variables. RESULTS: Of 343 enrolled patients, 321 were evaluated for efficacy. All primary efficacy endpoints were met: superiority was demonstrated for gadobutrol-enhanced versus unenhanced MR images (P < 0.0001 in all cases) for lesion enhancement, border delineation, and internal morphology. Noninferiority was met for mean number of lesions detected. There were improvements in the sensitivity of malignant lesion detection, without a loss in specificity, exact-match diagnostic accuracy, and reader confidence. Treatment-related adverse events were reported in 4.1% (n = 14); all were nonserious. CONCLUSION: Gadobutrol 1.0M is an effective and well-tolerated contrast agent for CNS MRI.