title: Efficacy of sonazoid (perflubutane) for contrast-enhanced ultrasound in the differentiation of focal breast lesions: phase 3 multicenter clinical trial.
abstract: OBJECTIVE
  The objective of our study was to compare the efficacy of contrast-enhanced ultrasound (CEUS) using the ultrasound contrast agent Sonazoid (perflubutane) with unenhanced ultrasound and supplementary contrast-enhanced MRI in the differential diagnosis (benign vs malignant) of focal breast lesions. The safety of Sonazoid was also assessed in this study.
  
  
  METHODS
  A total of 127 patients with focal breast lesions were enrolled in this study at five centers in Japan. Three reviewers who were blinded to the patient characteristics independently assessed the ultrasound images and MR images in a randomized sequence. The accuracy, sensitivity, and specificity of CEUS, unenhanced ultrasound, and supplementary contrast-enhanced MRI for the differential diagnosis were compared using generalized estimating equation analyses. Diagnostic confidence was also assessed.
  
  
  RESULTS
  The accuracy of CEUS was significantly higher than that of unenhanced ultrasound (87.2% vs 65.5%, respectively; p < 0.001). In addition, CEUS showed significantly higher specificity, although the improvement in sensitivity was not statistically significant. The accuracy and specificity were significantly higher with CEUS than with contrast-enhanced MRI, but the improvement in sensitivity was not statistically significant. The area under the curve in a receiver operating characteristic analysis was significantly greater with CEUS than with unenhanced ultrasound. The incidence of adverse events was 11.4% and the incidence of adverse drug reactions was 3.3%. All adverse drug reactions were mild.
  
  
  CONCLUSIONS
  CEUS using Sonazoid was confirmed to be superior to unenhanced ultrasound for the differential diagnosis (benign vs malignant) of focal breast lesions in terms of diagnostic accuracy with no serious adverse reactions.
authors.affiliation: 1 Department of Diagnostic Imaging, Jikei University Hospital, 3-19-18 Nishi-Shimbashi, Minato-ku, Tokyo 105-8471, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Ito
authors.forename: Etsuo
authors.initials: E
authors.lastname: Takada
authors.forename: Kiyoka
authors.initials: K
authors.lastname: Omoto
authors.forename: Toshiko
authors.initials: T
authors.lastname: Hirai
authors.forename: Fuminori
authors.initials: F
authors.lastname: Moriyasu
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D003287:Contrast Media; D003937:Diagnosis, Differential; D005260:Female; D005290:Ferric Compounds; D019786:Gadolinium DTPA; D006801:Humans; D007501:Iron; D008279:Magnetic Resonance Imaging; D008536:Meglumine; D008875:Middle Aged; D009942:Organometallic Compounds; D010087:Oxides; D012680:Sensitivity and Specificity; D016217:Ultrasonography, Mammary
chemical_list: D003287:Contrast Media; D005290:Ferric Compounds; D009942:Organometallic Compounds; D010087:Oxides; C069727:Sonazoid; D008536:Meglumine; C064925:gadodiamide; D007501:Iron; D019786:Gadolinium DTPA; C072417:gadoterate meglumine