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

Abstract

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.

Keywords: 3D ultrasound imaging; breast cancer; contrast-enhanced ultrasound; harmonic imaging; subharmonic imaging.

Figure 1.

Example of a 1.93 × 1.49 cm invasive ductal carcinoma imaged in a 68-year-old woman. A, Baseline grayscale imaging. B, Baseline PDI demonstrating marked vascularity throughout the lesion. C, Visualization of the lesion in 3D HI mode with contrast enhancement using 4DView. Multiple individual 2D imaging planes across the lesion volume (the slice separation was 2 mm) are shown. D, Visualization of the lesion in 3D SHI mode with contrast enhancement using 4DView. Notice the marked enhancement seen compared to the 3D HI images.

Figure 2.

Overall clinical assessments. A, ROC curves for grayscale ultrasound, PDI, 3D HI, and 3D SHI as well as SoC imaging (mammography and/or ultrasound) with A_z’s of 0.83, 0.82, 0.85, 0.82, and 0.72, respectively. The diagnostic accuracy of SoC imaging was significantly lower than those of the ultrasound modes (P < .03). B, ROC curves for the subset of lesions that demonstrated contrast-enhanced flow (A_z’s of 0.82–0.83).

Figure 3.

ROC curves for the best regression model combining the heterogeneity ratio with the central SHI perfusion parameter and grayscale ultrasound evaluations split by reader. Diagnostic accuracies were 0.90 (UCSD reader1), 0.91 overall, 0.93 (TJU reader 1), 0.97 (TJU reader 2), and 1.00 (UCSD reader 2).