Monitoring Neoadjuvant Chemotherapy for Breast Cancer by Using Three-dimensional Subharmonic Aided Pressure Estimation and Imaging with US Contrast Agents: Preliminary Experience

Abstract

Purpose To determine whether three-dimensional subharmonic aided pressure estimation (SHAPE) and subharmonic imaging can help predict the response of breast cancer to neoadjuvant chemotherapy. Materials and Methods In this HIPAA-compliant prospective study, 17 women (age range, 45-70 years) scheduled to undergo neoadjuvant therapy for breast cancer underwent ultrasonography (US) immediately before therapy and at completion of 10%, 60%, and 100% of chemotherapy. All patients provided written informed consent. At each examination, radiofrequency data were collected from SHAPE and subharmonic imaging during infusion of a US contrast agent. Maximum-frequency magnitude and mean intensity were calculated for SHAPE and subharmonic imaging. The signal differences in the tumor relative to the surrounding area were compared with the final treatment response by using the Student t test. Results Four patients left the study, and data from two patients were discarded because of technical problems. Eight patients completed the entire imaging protocol, and an additional three patients dropped out after the imaging session at completion of 10% of chemotherapy as a result of disease progression (these patients were counted as nonresponders). Patients' imaging outcomes consisted of six responders (tumor volume reduction >90%) and five partial responders or nonresponders. The results at completion of 10% of therapy showed that the subharmonic signal increased more in the tumor than in the surrounding area for responders than in partial responders or nonresponders (mean ± standard deviation, 3.23 dB ± 1.41 vs -0.88 dB ± 1.46 [P = .001], respectively, for SHAPE and 1.32 dB ± 0.73 vs -0.82 dB ± 0.88 [P = .002], respectively, for subharmonic imaging). Moreover, three patients whose tumor measurements initially increased were correctly predicted to be responders with SHAPE and subharmonic imaging after completion of 10% of therapy. Conclusion SHAPE and subharmonic imaging have the potential to help predict response to neoadjuvant chemotherapy for breast cancer as early as completion of 10% of therapy, albeit on the basis of a small sample size. RSNA, 2017 Online supplemental material is available for this article.

Impact of hydrostatic pressure on phase-change contrast agent activation by pulsed ultrasound

“…A more recent experiment in rats with breast cancer xenografts also demonstrated a linear relationship between TIP and SHAPE measurements (r ¼ 0:69; p < 0:01) (Halldorsdottir et al, 2017). Albeit based on a small sample size, it has been concluded that SHAPE has potential to help predict response to neoadjuvant chemotherapy for breast cancer as early as completion of one cycle of therapy (Nam et al, 2017). Despite these encouraging results, the average error associated with these in vivo US-based SHAPE measurements has been reported to exceed 6 mm Hg (Halldorsdottir et al, 2017) so improvements in pressure estimation technology and accuracy may be needed if this treatment indicator is to be adopted in clinical practice.…”

Improvement of Detection Sensitivity of Microbubbles as Sensors to Detect Ambient Pressure

“…To date, there are numerous reports about microbubbles as sensors for the local blood pressure measurements through detecting disappearance time of free bubbles [5,6], shift of the first harmonic or subharmonic resonance frequency [4,7,8,9,10,11,12], or amplitude variation of the scattered echo of microbubbles [1,3,10,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30]. Among them, amplitude variation of the scattered echo is most attractable and promising for clinical application.…”

Optimal Control of SonoVue Microbubbles to Estimate Hydrostatic Pressure

“…In addition to SonoVue, other microbubble ultrasound contrast agents, such as Sonazoid and Definity, have been investigated as potential pressure sensors. These have shown potential as noninvasive pressure sensors in the right ventricle [5], for diagnosing portal hypertension [39], and for estimating tumor interstitial fluid pressure in breast cancer [40]. One disadvantage of using SonoVue, compared with Sonazoid or Definity, is its nonunique subharmonic amplitudes from 0-to 200-mmHg hydrostatic pressures.…”