Tumor characterization and treatment monitoring of postsurgical human breast specimens using harmonic motion imaging (HMI)

Yang Han, Shutao Wang, Hanina Hibshoosh, Bret Taback, Elisa Konofagou, Yang Han, Shutao Wang, Hanina Hibshoosh, Bret Taback, Elisa Konofagou

Abstract

Background: High-intensity focused ultrasound (HIFU) is a noninvasive technique used in the treatment of early-stage breast cancer and benign tumors. To facilitate its translation to the clinic, there is a need for a simple, cost-effective device that can reliably monitor HIFU treatment. We have developed harmonic motion imaging (HMI), which can be used seamlessly in conjunction with HIFU for tumor ablation monitoring, namely harmonic motion imaging for focused ultrasound (HMIFU). The overall objective of this study was to develop an all ultrasound-based system for real-time imaging and ablation monitoring in the human breast in vivo.

Methods: HMI was performed in 36 specimens (19 normal, 15 invasive ductal carcinomas, and 2 fibroadenomas) immediately after surgical removal. The specimens were securely embedded in a tissue-mimicking agar gel matrix and submerged in degassed phosphate-buffered saline to mimic in vivo environment. The HMI setup consisted of a HIFU transducer confocally aligned with an imaging transducer to induce an oscillatory radiation force and estimate the resulting displacement.

Results: 3D HMI displacement maps were reconstructed to represent the relative tissue stiffness in 3D. The average peak-to-peak displacement was found to be significantly different (p = 0.003) between normal breast tissue and invasive ductal carcinoma. There were also significant differences before and after HMIFU ablation in both the normal (53.84 % decrease) and invasive ductal carcinoma (44.69 % decrease) specimens.

Conclusions: HMI can be used to map and differentiate relative stiffness in postsurgical normal and pathological breast tissues. HMIFU can also successfully monitor thermal ablations in normal and pathological human breast specimens. This HMI technique may lead to a new clinical tool for breast tumor imaging and HIFU treatment monitoring.

Keywords: HIFU monitoring; HMIFU; Human breast tumor.

Figures

Fig. 1
Fig. 1
Schematic of harmonic motion imaging (HMI) system with experiment setup. a Block diagram of HMI system. The red region indicates the focus of the focused ultrasound (FUS) transducer. b The 1D HMI system comprised of a single-element FUS transducer (outer diameter 80 mm, inner diameter 16.5 mm) coaligned with a single-element pulse-echo transducer (diameter 15 mm). c The 2D HMI system consisted of a 93-element FUS phase array transducer (outer diameter 110 mm, inner diameter 41 mm) and a 64-element phase array imaging probe
Fig. 2
Fig. 2
3D harmonic motion imaging (HMI) displacement images of normal breast, invasive ductal carcinoma (IDC), and fibroadenoma (FA) tissue. a Gross pathology photograph of a normal breast specimen mounted on the gel matrix. The 3D reconstructed HMI of the selected tissue is shown (b) before and (c) after harmonic motion imaging for focused ultrasound (HMIFU) ablation. d Gross pathology photograph of a IDC specimen mounted on the gel matrix. The 3D reconstructed HMI of the selected tissue is shown (e) before and (f) after HMIFU ablation. g Gross pathology photograph of an FA specimen mounted on the gel matrix. The 3D reconstructed HMI of the selected tissue is shown (h) before and (i) after HMIFU ablation. The brighter the color, the higher the HMI displacement and the lower relative stiffness, and vice versa
Fig. 3
Fig. 3
Harmonic motion imaging (HMI) displacement change between before and after ablation. a Nine normal, five invasive ductal carcinoma (IDC), and one fibroadenoma (FA) specimens were imaged with the 1D HMI system. b Ten normal, ten IDC, and one FA specimens were imaged with the 2D HMI system. c Combined results with both HMI systems. *p < 0.05, **p < 0.001, and ****p < 0.00001
Fig. 4
Fig. 4
Harmonic motion imaging for focused ultrasound (HMIFU) ablation monitoring in 2D overlaying on B-mode images in (a) normal breast and (b) IDC tissue. Tissue motion during heating is denoted by alternating red and blue. Red represents the motion moving toward the transducer, and blue represents the motion moving away from the transducer. Peak negative harmonic motion imaging displacement frames during a 50-Hz cycle at five representative timepoints were selected from the HMIFU treatment monitoring sequence to show the decrease of focal displacement as the thermal lesion forms
Fig. 5
Fig. 5
Examples of hematoxylin and eosin staining of harmonic motion imaging for focused ultrasound-ablated normal breast (a–c), invasive ductal carcinoma (d–f), and fibroadenoma (g–i) tissues. In (a), (d), and (g), scale bars indicate 4 mm; in the rest of the images, scale bars indicate 0.1 mm. In (b), (e), and (h), high-magnification images display unablated regions taken within the corresponding black frames. In (c), (f), and (i) high-magnification images display ablated regions taken within the corresponding blue frames. The ablated regions show discrete hypereosinophilic areas reflecting changes occurring in the collagenous stroma as well as cautery-like “streaming” phenomena (arrows) in the HIFU-ablated epithelial regions. The changes seen in the epithelium and/or nuclei are (nonneoplastic, benign, or malignant) reminiscent of what is seen in tissue exposed to electrocautery change. Surrounding tissues remained histologically intact

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