3D Harmonic and Subharmonic Imaging for Characterizing Breast Lesions: A Multi-Center Clinical Trial

Flemming Forsberg, Catherine W. Piccoli, Anush Sridharan, Annina Wilkes, Alexander Sevrukov, Haydee Ojeda-Fournier, Robert F. Mattrey, Priscilla Machado, Maria Stanczak, Daniel A. Merton, Kirk Wallace, John R. Eisenbrey

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Objective: Breast cancer is the most frequent type of cancer among women. This multi-center study assessed the ability of 3D contrast-enhanced ultrasound to characterize suspicious breast lesions using clinical assessments and quantitative parameters. Methods: Women with suspicious breast lesions scheduled for biopsy were enrolled in this prospective, study. Following 2D grayscale ultrasound and power Doppler imaging (PDI), a contrast agent (Definity; Lantheus) was administrated. Contrast-enhanced 3D harmonic imaging (HI; transmitting/receiving at 5.0/10.0 MHz), as well as 3D subharmonic imaging (SHI; transmitting/receiving at 5.8/2.9 MHz), were performed using a modified Logiq 9 scanner (GE Healthcare). Five radiologists independently scored the imaging modes (including standard-of-care imaging) using a 7-point BIRADS scale as well as lesion vascularity and diagnostic confidence. Parametric volumes were constructed from time-intensity curves for vascular heterogeneity, perfusion, and area under the curve. Diagnostic accuracy was determined relative to pathology using receiver operating characteristic (ROC) and reverse, step-wise logistical regression analyses. The κ-statistic was calculated for inter-reader agreement. Results: Data were successfully acquired in 219 cases and biopsies indicated 164 (75%) benign and 55 (25%) malignant lesions. SHI depicted more anastomoses and vascularity than HI (P <.021), but there were no differences by pathology (P >.27). Ultrasound achieved accuracies of 82 to 85%, which was significantly better than standard-of-care imaging (72%; P <.03). SHI increased diagnostic confidence by 3 to 6% (P <.05), but inter-reader agreements were medium to low (κ < 0.52). The best regression model achieved 97% accuracy by combining clinical reads and parametric SHI. Conclusions: Combining quantitative 3D SHI parameters and clinical assessments improves the characterization of suspicious breast lesions.

Original languageEnglish (US)
Pages (from-to)1667-1675
Number of pages9
JournalJournal of Ultrasound in Medicine
Issue number7
StatePublished - Jul 2022
Externally publishedYes


  • 3D ultrasound imaging
  • breast cancer
  • contrast-enhanced ultrasound
  • harmonic imaging
  • subharmonic imaging

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging


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