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Breast Lesion Detection and Characterization with Contrast-Enhanced Magnetic Resonance Imaging: Prospective Randomized Intra-individual Comparison of Gadoterate Meglumine versus Gadobenate Dimeglumine at 3 Tesla

Paola Clauser¹, Thomas H. Helbich¹, Panagiotis Kapetas¹, Maria Bernathova¹, Katja Pinker¹, and Pascal A.T. Baltzer¹

¹Medical University of Vienna, Vienna, Austria

Synopsis

The aim of our study was to compare a 0.075 mmol/kg dose of gadobenate dimeglumine, with a 0.15 mmol/kg dose of gadoterate meglumine for breast lesion detection and characterization at 3T-MRI. Patients included underwent two examinations, 24-72h apart, one with gadobenate and one with gadoterate administered in randomized order. Three readers evaluated the examinations and diagnostic performance was calculated and compared. 104 women with 142 histologically verified breast lesions (109 malignant, 33 benign) were included. Detection with gadobenate was comparable to gadoterate (p>0.165). Gadobenate demonstrated significantly higher specificity and accuracy (p<0.007). Multivariate analysis demonstrated reader-independent superior diagnostic accuracy with gadobenate.

Introduction

Magnetic resonance imaging (MRI) of the breast enhanced with gadolinium-based contrast agents (GBCAs) enables breast cancer detection with a sensitivity above 90%. ^1,2 However this substantially greater sensitivity compared with mammography and ultrasound, comes at the expense of more benign breast biopsies in up to 35% of cases. ^1,3 In this context a contrast agent that allows a reduction of false positive findings would be beneficial in terms of reduced costs and reduced patient anxiety. Of the contrast agents available for MRI of the breast, gadobenate dimeglumine has markedly higher r1 relaxivity. ⁴ Studies have shown that this higher r1 relaxivity translates into greater signal intensity enhancement and thus better lesion visualization. ^5–9 Based on available evidence, we hypothesized that a reduced dose of the high relaxivity GBCA gadobenate might prove effective for breast lesion detection and characterization when compared to a two-fold higher dose of a standard relaxivity comparator GBCA under otherwise identical imaging conditions. The aim of this prospective, randomized, single-center study was to intra-individually compare a three-quarter (0.075 mmol/kg bodyweight) dose of gadobenate with a two-fold higher dose (0.15 mmol/kg bodyweight) of the standard relaxivity GBCA gadoterate in terms of non-inferiority for breast lesion detection and characterization at 3 Tesla.

Methods

Eligible for this IRB-approved prospective, randomized, intra-individual comparative study were patients with imaging abnormalities (BI-RADS 0, 4 or 5) on conventional breast imaging. Each patient underwent two examinations, 24-72h apart, one with gadobenate dimeglumine and the other with gadoterate meglumine administered in randomized order. Both examination were performed at 3T using identical sequence and timing parameters including high spatiotemporal resolution dynamic CE, T2w-TSE, STIR-T2w and DWI sequences. Two examinations, 24-72h apart, were performed with contrast agents administered in randomized order. Histopathology was the standard of reference. Three blinded, off-site breast radiologists evaluated the examinations. Lesion detection, sensitivity, specificity, and accuracy were calculated per-lesion and per-region and compared by univariate and multivariate analysis.

Results

109 patients were recruited. Five patients were excluded due to technical problems or the lack of reference standard leaving 104 women with 142 histologically verified breast lesions (109 malignant and 33 benign) available for evaluation. The detection rate with gadobenate (84.5-88.7%) was not inferior to gadoterate (84.5%-90.8%), p>0.165. At per-region analysis, gadobenate demonstrated higher specificity (96.4%-98.7% vs. 92.6-97.3%, p<0.007) and accuracy (96.3-97.8% vs. 93.6-96.1%, p≤0.001) compared to gadoterate, for all three readers. Gadobenate allowed a reduction in false positives of up to 58%. Multivariate analysis demonstrated a reader-independent superior diagnostic accuracy with gadobenate.

Discussion

Concern over gadolinium deposition in the brain following GBCA administration has led to diverging action by regulatory authorities around the world. The European Medicines Agency (EMA) recommended the suspension of certain linear GBCAs, excepting those agents with liver-specific properties. ¹⁰ Restrictions on linear GBCAs could be lifted if evidence is provided of new benefits that outweigh the potential, as yet unproven, risks of gadolinium deposition. The results of our study show that a three-quarter dose (0.075 mmol/kg) of gadobenate is not inferior to a two-fold higher dose (0.15 mmol/kg) of gadoterate for breast lesion detection. Specifically, three blinded, unaffiliated readers showed that gadobenate is superior for lesion characterization, permitting greater specificity and diagnostic accuracy at lower dose due to a reduced number of false positive findings. Given the absence of any clinical signs or symptoms associated with Gd retention; that Gd retention and, increasingly, visible T1-hyperintensity in the dentate nucleus occurs with both linear and macrocyclic GBCAs; and that there have been no unconfounded cases of NSF with gadobenate suggesting inherent stability in vivo, ¹¹ we feel the benefit-risk balance for low dose breast MRI examinations with gadobenate should be considered positive. Our study has several limitations: it was a single-center observational study and only cases for which a histological examination was performed were included, leading to a possible selection bias in favor of more suspicious or complicated lesions, and leading to a high rate of malignancy. The dose of gadoterate used (0.15 mmol/kg) was higher than the approved dose (0.1 mmol/kg), which might be considered one explanation for the higher rate of false-positive findings with this agent. However, side-by-side evaluation of examinations with both agents revealed no differences in contrast enhancement or image quality and no obvious reasons for a higher number of false-positives with gadoterate based on contrast enhancement.

Conclusion

In conclusion, a three quarter dose (0.075 mmol/kg) of high-relaxivity gadobenate is not inferior to a two-fold higher dose (0.15 mmol/kg) of lower relaxivity gadoterate for breast lesion detection and characterization.

Acknowledgements

The authors would like to thank the three readers, Luca Carbonaro, MD, Matthias Dietzel, MD, and Federica Pediconi, MD, for their dedicated effort. Thanks to Claudio Spick, MD, for the assistance in data collection. Thanks to Miles Kirchin for the help during text review. This study was supported by Bracco Imaging. The authors are solely responsible for the content of this article.

References

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Proc. Intl. Soc. Mag. Reson. Med. 26 (2018)

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