An in vitro and in vivo study on extracorporeal transducer optimization for high-intensity focused ultrasound to improve the safety and efficacy of breast tumor ablation

Abstract

Objective

To observe the characteristics of a new extracorporeal high intensity focused ultrasound transducer, titled Haifu system JCQ-B, and to compare its safety and efficacy for breast ablation with the standard Haifu system JC transducer.

Materials and methods

Ox liver with pig skin and pork ribs were prepared in a semi-sphere shape, served as in vitro acoustic model. The udders of female goats were used as in vivo acoustic model. Both in vitro and in vivo models were ablated by either JCQ-B or JC transducer. The morphology of biological focal region (BFR), the coagulative necrosis volume, and the temperature increase were observed and compared.

Results

The BFR morphology of JCQ-B transducer was circular both in vitro and in vivo, with a length-width ratio close to one. Under the same sonication parameters (sonication power, time and depth in tissue), coagulation necrosis volume caused by JCQ-B transducer was larger than that caused by JC transducer both in vitro and in vivo. The increase in temperature in the near and far acoustic pathways with JCQ-B transducer was significantly lower than that of JC transducer in vitro. After receiving high sonication energy during in vivo experimentation, there were no complications observed after the ablation of JCQ-B transducer, while small skin damage was observed after the ablation of JC transducer.

Conclusions

The JCQ-B transducer improved the safety and efficacy of treatment by optimizing BFR morphology and ablation efficiency, which could be applied in the treatment of breast tumor.

Keywords:

• High-intensity focused ultrasound
• transducer
• biological focal region
• breast tumor

1. Introduction

From the 1990s, high intensity focused ultrasound (HIFU) has been widely used in clinical practice to noninvasively treat a variety of solid tumors, including hepatocellular carcinoma, pancreatic cancer, uterine fibroids, breast cancer and fibroadenomas [1–4]. Ultrasound beams generated from an extracorporeal piezoelectric transducer can pass through overlying skin and surrounding tissues and precisely focus on a target region. Ultrasonic energy deposition in targeted tissue can result in a rapid temperature increase, which causes irreversible damage, coagulative necrosis of cells by thermal effect, and mechanical damage by mechanical effect and cavitation effect [5,6].

Breast is a superficial organ attached to the pectoralis major. The acoustic pathway during treatment of breast tumors is relatively simple in comparison to more complicated pathways involved in treatment of pancreatic and uterine pathologies, as the intra-abdominal location can increase the impact on surrounding tissues and vital organs. The focused ultrasound beams only need to pass through skin and normal breast tissue to ablate the breast lesion. Thus, breast tumors, including breast cancer and fibroadenomas, are thought to be suitable indications for HIFU ablation using an extracorporeal transducer. In the past two decades, several studies have shown HIFU to be effective and safe for breast cancer and fibroadenoma treatment [7,8]. However, complications of skin burn and pectoralis major muscle injury were also reported [7,9]. Since breast lesions are anatomically close to the skin and the pectoralis major muscle, during ablation, the skin area inside the near acoustic field of the ultrasound pathway is not as large as that of intra-abdominal lesions. In addition, depending on the geometric size and acoustic parameters of the HIFU transducers, the size of the acoustic focal region (AFR) of existing extracorporeal transducers is typically 1–3 mm in width and approximately 8–10 mm in length [10]. This characteristic of the AFR made the skin in the near acoustic field and the pectoralis major muscle in the far acoustic field more vulnerable to energy deposition than the tissues perpendicular to the ultrasound propagation direction. The above mentioned two points make it difficult to completely ablate breast tumor and avoid the surrounding tissue damage at the same time.

In order to improve the safety and efficacy of HIFU ablation for breast tumors, a new transducer was designed according to breast anatomic characteristics to address the limitations of current transducers [11]. And since the biological effects of ultrasound energy deposition inside the human body differs greatly from its acoustic properties displayed in an ideal acoustic field, the biological focal region (BFR) should be well explored to better understand the biological acoustic environment and acoustic intensity at the focus in tissues. Hence, the main objective of this preclinical study was to observe the characteristics of this newly designed transducer, and to compare the safety and efficacy between this transducer with previously used transducer in vitro and in vivo.

2. Materials and methods

Animal experiments were performed in compliance with guidelines of the Animal Ethics Committee of Chongqing Medical University (IACUC-CQMU-2022-0012). The udder models were established using healthy female goats.

2.1. Preparation of in vitro model

Considering that the acoustic parameters between ox liver tissue and breast fat and breast gland were in similar range (Supplementary Table 1) and fresh animal breast tissue was difficult to obtain, pig skin, fresh ox liver and pig ribs were used to make the in vitro tissue acoustic model. Pig skin was first degassed together with ox liver using a vacuum for 30–60 min. Then, the ox liver was trimmed to a semi-sphere shape with 10 cm-diameter to mimic the shape of breast, with pig skin as the outermost layer and pork ribs as the innermost layer (Figure 1(a)). To minimize tissue exposure to air, the whole procedure of trimming and assembling was performed under water. After the model was attached onto a holder, it was sonicated using either the Focused Ultrasound Tumor Therapeutic System with a traditional transducer, called Haifu system JC, or the Focused Ultrasound Ablation System for Breast (Chongqing Haifu Med. Tec. Co., Ltd.) with a newly designed transducer, called Haifu system JCQ-B. Ox liver in the center was swapped between each experiment (Figure 1(b)). To measure temperature, several thermocouples were inserted into pre-set points of the model, including subcutaneous area, 1 cm away from the focus in the near field of acoustic pathway and 1 cm away from the focus in the far field (Figure 1(b), right).

Figure 1. Experiment schematics and setup. (a) overall schematic diagram of complicated tissue acoustic model (pig skin, ox liver and pig rib); (b) complicated tissue acoustic model (left) and location diagram of thermocouples (right); (c) animal experiment setup images; (d) typical real-time sonographic image of HIFU treatment.

2.2. Preparation of in vivo goat udder model

After fasting for 24 h, goats were intraperitoneally injected 1–1.5 ml/kg chloral hydrate (0.2 g/mL) to induce anesthesia, and then chloral hydrate was intravenously given to maintain anesthesia. The skin was shaved, degreased with 75% alcohol and degassed with a vacuum. Then, the goat was secured using an animal stent, which was placed on the JC or JCQ-B transducers for sonication (Figure 1(c)). Breast skin was photographed before, immediately after, and 7 days after ablation. Ultrasound (US) imaging of the udder was conducted 7 days after sonication. Afterwards, the goat was sacrificed to retrieve the ablated udder and surrounding tissues in acoustic pathway, including breast skin, fascia and abdominal muscle, for further experimentation.

2.3. Transducer sonication

Ablation was performed with either the JC or the JCQ-B transducer (Figure 1(d)). The parameters of the single-element JC transducer have been described in previous studies [12,13], which was characterized with a frequency of 1.0 MHz, a diameter of 20 cm, a focal length of 150 mm, a focal region of 8.2 × 3.1 × 3.2 mm³ at –6 dB levels in degassed water and a power range between 0-400 W. To optimize the effect of focused ultrasound sonication on the breast, a new single-element transducer was designed and developed according to the anatomical characteristics of the breast (named JCQ-B). The new transducer had a frequency of 1.0 MHz, a diameter of 22 cm, a focal length of 120 mm, a focal region of 3.7 × 1.8 × 1.8 mm³ at –6dB levels in degassed water and a power range between 0–400 W. Different sonication powers (100–400 W), sonication times (1–3 s) and tissue depths (30–50 mm) were used according to the protocol. A real-time ultrasound device (DC-8, Mindray Med. Int.) was used to monitor the possible hyperechoic change after ablation.

2.4. Parameters evaluation

In order to compare the focus morphology of the two transducers in the ideal and inorganic acoustic field, a fast shutter speed camera (D3X, Nikon, Japan) was used to quickly take pictures of the focal area when sonicated in degassed water or cis-polybutadiene rubber. The range of cavitation bubbles that appeared in the sonication was defined as the focal area. For the observation of focal area and BFR morphology, the necrosis length along the direction of the ultrasonic beams and the width of the direction perpendicular to the beams were measured by ruler. The length-width ratio was calculated. To get coagulative necrosis volume, an ellipsoid formula was used: Volume (mm³) = 4/3 × π × 1/2 length (mm) × 1/2 width (mm) × 1/2 thickness (mm). For sonication efficiency evaluation, energy-efficiency factor (EEF), defined as the acoustic energy delivered for ablating 1 mm³ of the tissue [14,15], was calculated with the following equation: EEF (J/mm³) = P·t/V, in which P (W) represented the sonication power, t (s) represented the sonication time, and V (mm³) represented the coagulative necrosis volume.

2.5. 2, 3, 5-Triphenyl tetrazolium chloride staining and hematoxylin and eosin staining

After specimens of ablated udder were retrieved, cell viability was determined by 2, 3, 5-Triphenyl tetrazolium chloride (TTC) staining [16]. Sliced specimens were immersed in a box with 2% TTC solution, which was placed in a 37 °C water bath for 10–20 min. For hematoxylin and eosin (H&E) staining, the tissues were embedded in paraffin and cut into 2–3 μm sections on glass slides. After dehydration, the sections were stained with hematoxylin and eosin for microscopic examination.

2.6. Transmission electron microscopy analysis

Normal and ablated udder tissues were freshly taken followed by being fixed in 2% glutaraldehyde at 4 °C for 8–10 h, and re-fixed by 2% osmium tetroxide for 2 h. After dehydration and embedding, sections with a thickness of 0.1 μm were stained with uranyl acetate and lead citrate. Then, the sections were examined with Transmission electron microscopy (TEM) at 60 kV (JEM-1400PLUS, JEOL).

2.7. Statistical analysis

SPSS software (SPSS 21.0, IBM, USA) was used for statistical analysis. Normally distributed continuous variables were presented as the mean ± standard deviation. The student’s t-test was used to compare the data between the two groups. Statistical significance was defined as a P value < 0.05.

3. Results

3.1. Comparison of focal morphology between two transducers in an ideal and an inorganic acoustic field

As shown in Figure 2(a and b), when the power of 200 W was continuously generated in an ideal acoustic field with degassed water, the JC transducer focal shape was like a lancet, while the JCQ-B transducer focal shape was like a dot. When the energy of 500 J (250 W × 2s) was generated in the inorganic acoustic field made with cis-polybutadiene rubber, the appearance of cavitation bubbles in the rubber could be seen in the focal area, and the focus shape of each transducer was similar as in degassed water (Figure 2(c and d)). As shown in Table 1, the length, width and length-width ratio of the focal shape generated by JC transducer in cis-polybutadiene rubber (n = 5) were 7.27 ± 1.47 cm, 2.57 ± 0.33 cm and 2.82 ± 0.32, respectively, while which of the focus shape generated by JCQ-B transducer in cis-polybutadiene rubber (n = 5) were 4.40 ± 0.70 cm, 3.98 ± 0.51 cm and 1.11 ± 0.15, respectively. There were statistically significant differences between the two groups (p < 0.05).

Figure 2. Comparison of the Morphological differences of focus between the JC and JCQ-B transducers. (a and b), the focal morphology (orange arrow) in an ideal acoustic field (degassed water). (c and d), the focal morphology (orange arrow) in an inorganic acoustic field (cis-polybutadiene rubber). (e and f), the BFR morphology in ox liver in the tissue acoustic model. BFR, biological focal region.

Table 1. Comparison of the length, width and length-width ratio between the JC and JCQ-B transducers in cis-polybutadiene rubber (sonication energy: 500 J) and ox liver tissue acoustic model (sonication energy: 1500 J).

	Cis-polybutadiene rubber			Ox liver tissue acoustic model
	JC (n = 5)	JCQ-B (n = 5)	P value	JC (n = 10)	JCQ-B (n = 13)	P value
Average length (mm)	7.27 ± 1.47	4.40 ± 0.70	<0.05	6.19 ± 1.27	4.59 ± 1.11	<0.05
Average width (mm)	2.57 ± 0.33	3.98 ± 0.51	<0.05	1.97 ± 0.55	4.13 ± 1.04	<0.05
Average length-width ratio	2.82 ± 0.32	1.11 ± 0.15	<0.05	3.24 ± 0.72	1.13 ± 0.24	<0.05

3.2. Comparison of the biological effects and safety between two transducers in vitro

All the in vitro experiments were conducted using the in vitro model mentioned in Methods 2.1. The BFR morphology was first compared between the transducers in tissue acoustic model. When 1500 J (300 W × 5s) of sonication energy was generated at the depth of 40 mm, the BFR shapes of the JC (n = 10) and JCQ-B (n = 13) transducers in the model were like a lancet and an oval, respectively (Figure 2(e and f)). Detailed data of BFR length, width and length-width ratio of two transducers in tissue acoustic model were shown in Table 1.

Then, the biological effect and safety of the transducers were compared. When a single point was sonicated under the same sonication parameters, including power (300 W), sonication time (5s) and tissue depth (40 mm), hyperechoic changes in focal area could be generated by both transducers (Figure 3(a)). The coagulative necrosis volume caused by the JCQ-B transducer was about 1.5 times of that caused by the JC transducer (p < 0.05, Figure 3(b)), while the EEF of the JCQ-B transducer was around two thirds of that of the JC transducer (p < 0.05, Figure 3(c)). In regards to tissue safety in the acoustic pathway, the temperature rise during the sonication of the JCQ-B transducer was significantly lower than that of the JC transducer at all the temperature measurement points (p < 0.05, Figure 3(d-f)).

Figure 3. Hyperechoic changes in focal area in in vitro model and comparison of the biological effects and safety between the JC and JCQ-B transducers in ox liver tissue acoustic model under the same sonication parameters. (a) hyperechoic changes in the focal area generated by JC and JCQ-B transducers. (b) coagulation necrosis volume; (c) EEF, energy efficiency factor; (d) the increase of temperature in the subcutaneous area; (e) the increase of temperature in the near acoustic field; (f) the increase of temperature in the far acoustic field.

3.3. Comparison of the efficacy and safety between two transducers in vivo

The efficacy and safety of the JCQ-B transducer were further observed in the goat udder model. When a single point of about 30 mm depth was sonicated under the power of 400 W with a sonication time of 15s (energy: 6000 J), hyperechoic changes appeared in focal region right after sonication (Figure 4(a and b)). Seven days after sonication, a persistent hyperechoic change in the ablated area was seen on US imaging (Figure 4(c and d)). Macroscopically, the coagulation area could be easily identified with the whitish feature and surrounded by a thin red hyperemic zone. After TTC staining, no viable cells were found in the ablated area, while the hyperemic zone and surrounding normal tissue were stained red (Figure 5(a and b)). Histological findings demonstrated the typical signs of coagulative necrosis and mechanical damage in the ablated area, including cellular destruction, eosinophilic cytoplasm, nuclei fragmentation and lysis. Vascular destruction and erythrocyte aggregation were also observed. The hyperemia and edema zones were characterized with infiltration of inflammatory cells (Figure 5(c–i)). TEM showed the destruction of cell membrane integrity, fragmented nuclei and damaged mitochondria and other organelles of the cells within the ablated region, while no such changes in the surrounding normal cells were visualized (Figure 5(j–m)). In terms of safety, there was no skin damage observed in the near acoustic field and no fascia and abdominal muscle damage in the far acoustic field both macroscopically and microscopically (Figure 6(a–o)).

Figure 4. The US imaging of the goat mammary gland. (a) hypoechoic US imaging characteristics of the mammary gland before sonication. (b) hyperechoic scale change of US imaging appeared in the focus region after the JCQ-B transducer sonication (sonication energy: 6000 J). The US images of normal tissue (c) versus post-ablation tissue (d) in the mammary gland 7 days after sonication.

Figure 5. Pathologic images of the goat mammary gland after the JCQ-B transducer sonication. (a and b) macroscopic view of the ablated area before and after TTC staining. (c) a complete view of the ablated area and surrounding normal tissue with H&E staining (6.7×). (d and e) local magnification of (c) (white square, 40× and 100×, respectively). There was hyperemia and edema (H) between the coagulation area (C) and the normal tissue (N). (f-i) histological images of normal tissue (black square) (5f, 200× and 5h, 400×) and ablated tissue (white square) (5 g, 200× and 5i, 400×). (j-m), from (a) specimen, normal tissue (red arrow in a) and ablated tissue (white arrow in 5(a)) were taken. TEM images of normal tissue (5j, 6000× and 5 l, 12,000×) and ablated tissue were shown. (5k, 6000 × and 5 m, 10,000×).

Figure 6. Tissue safety in the acoustic pathway of the JCQ-B transducer (sonication energy: 6000 J). (a–c), goat breast skin before (6a), immediately after (6b) and 7 days (6c) after sonication. (d–f), no observed damage of the subcutaneous tissue (6d), the mammary gland surface (6e) and the fascia of abdominal wall (6f) after sonication in macroscopic view. (g–i), no histological skin tissue damage after sonication via H&E staining (6 g, 40×; 6h, 100×; 6i, 200×). (j–l), no histological tissue fascia damage after sonication by H&E staining (6j, 40×; 6k, 100×; 6 l, 200×). (m–o), no histological abdominal muscle tissue damage after sonication by H&E staining (6 m 40×; 6n, 100×; 6o, 200×). (p–u), safety comparison between the Haifu system JC and JCQ-B transducers. Before (6p), immediately after (6q) and 7 days (6r) after the JC transducer sonication, breast skin damage was observed in two locations (red oval). before (6s), immediately after (6t) and 7 days (6 u) after the JCQ-B transducer sonication, there was no breast skin damage.

Then, an in vivo comparison of the biological effects and safety was conducted between two transducers. As shown in Table 2, when a high sonication energy of 6000 J with the power of 400 W was applied to a single point in the same depth of goat udder, the average hyperechoic change emerging time caused by the JCQ-B transducer was shorter than that caused by the JC transducer (1.0 ± 0.0 s VS 1.7 ± 0.5 s, respectively, p < 0.05). Coagulative necrosis volume caused by the JCQ-B transducer was around 2.1 times of that caused by the JC transducer (Table 2, p < 0.05), while the average length-width ratio and EEF of the JCQ-B transducer was significantly lower than that of the JC transducer (p < 0.05). Immediately after sonication, there was no skin damage observed with the JCQ-B transducer, while two spots of skin damage were observed by the JC transducer, which scarred 7 days after sonication (Figure 6(p–u)). No subcutaneous tissue damage, and no hyperemia or fascia and abdominal wall damage in the acoustic pathway of both transducers was observed when the goats were sacrificed 7 days after sonication.

Table 2. Comparison of the length, width and length-width ratio between the JC and JCQ-B transducers with goat mammary Glands (sonication energy: 6000 J).

	JC (n = 6)	JCQ-B (n = 5)	P value
Average appearing time of hyperechoic change (s)	1.70 ± 0.50	1.00 ± 0.00	<0.05
Average length (mm)	17.00 ± 2.19	17.30 ± 1.59	>0.05
Average width (mm)	13.60 ± 1.52	19.98 ± 2.94	<0.05
Average length-width ratio	1.25 ± 0.12	0.88 ± 0.11	<0.05
Average necrosis volume (mm^3)	1748.46 ± 448.28	3729.68 ± 1283.95	<0.05
Average EEF (J/mm^3)	1.40 ± 0.30	1.00 ± 0.20	<0.05

4. Discussion

Over the last two decades, thermal ablation techniques have been increasingly used in clinical practice as the concept of minimal- and noninvasive treatment is widely accepted by clinical practitioners and patients. As a noninvasive thermal ablation treatment, HIFU has the particular benefits of preserving the breasts with no scars. Recently, several groups have applied this technique to treat patients with breast cancer and fibroadenoma [17,18]. However, the complete ablation was varied from 28–95% with the complications of mild to severe skin burn in different studies [7,19–21]. We speculated that one of the key reasons for the unsatisfied effect and safety of HIFU treating breast tumors in previous studies may be due to the design of transducer. Theoretically, AFR, defined as the region bounded by the acoustic pressure contour lying 6 dB below the peak acoustic pressure, is the most important characteristic of transducer, which could be calculated by computer software or be detected using a hydrophone [10]. The morphology of AFR was settled depending on the size, focal length and focusing ability of the transducer, not changing with the acoustic environment. The reported size of AFR of extracorporeal transducer with frequency of 1.0 MHz, especially the existing transducer mentioned in this study, was usually 8–10 mm in length and 1–3 mm in width [10,13,22]. This lancet-like shape made the tissue in the near field of acoustic pathway parallel to the direction of ultrasonic beam vulnerable to damage due to unwanted energy accumulation and deposition. As focused ultrasound has thermal effect on tissue and mechanical effect caused by cavitation and boiling, the result of this study indicated that all these effects might play an important role in ablation: the hyperechoic change of focal area during ablation might be caused by boiling and cavitation, the TTC and H&E staining results of tissue coagulative necrosis might be caused by thermal effect and the TEM result of cell destruction might be caused by mechanical effect due to boiling and cavitation in tissue. The interface between coagulative necrotic tissue and normal tissue in the near field may cause significant reflection and refraction of ultrasound and prevent the sound waves from spreading to the tissue behind the coagulative necrotic area, so the energy may increasingly accumulate in the near acoustic field. If the ultrasonic energy was excessively absorbed by the tissue in the near field, especially the skin, skin burn may occur [23]. Since breast was a semi-spherical organ and breast tumors usually were close to the skin, the clinical protocol of breast tumor HIFU ablation may fall into a dilemma of completely ablating the lesion but damaging the skin, or protecting the skin but incomplete ablation. The newly designed transducer used in present study seemed to overcome this dilemma, because the focus was very small with a dot-like shape (Figure 2(b)). The optimization of focal shape might be the result of shortened focal length and enlarged transducer diameter. It was known that the smaller the focus was, the better the focusing ability of the transducer was. However, the optimization of focus shape was just the first step for the adaptation of breast anatomy. Since the biologic effects of HIFU was not the same as its acoustic properties displayed in degassed water, which was influenced by a variety of factors when the ultrasonic beams propagated in the biologic tissue, including the reflection, refraction, scatter and diffraction of ultrasonic beam interfering with energy deposition, inhomogeneity of tissue structure and its functional status [24], it was important to validate the biologic effects of a new transducer before being used in clinical practice. For better understanding the biologic effects induced during HIFU ablation, Wang et al. first proposed the concept of “biological focal region” (BFR), which was defined as an individual coagulative necrosis induced by a single exposure of HIFU [25]. When BFR was compared between two transducers in vitro, we found that BFR morphology of the JCQ-B transducer was significantly changed with shortened length and elongated width. It indicated that the energy was more concentrated at the focal point. The new transducer not only modified BFR morphology, but also increased the ablation efficiency. When the same energy was given, necrosis volume produced using JCQ-B transducer was larger both in vitro and in vivo. Considering that the hyperechoic changes was present around 1s after sonication, this may be a sign of boiling, the boiling temperatures were reached faster in JCQ-B as focal intensity and heating rate at the focus were higher. And from the results that hyperechoic changes in real-time ultrasound, coagulative necrosis in H&E staining and destruction of subcellular structure in TEM, it was indicated that cavitation effects, thermal effects, and mechanical effects might be all involved in the ablation procedure. Compared with the previously used transducer, less energy with shortened sonication time was needed for new transducer when ablating the same volume of lesion. It was well-accepted that prolonged treatment duration could lead to increased risk of adverse events. As reported by a previous study, when large amounts of ultrasound energy were over accumulated in human body during HIFU treatment, the body’s regulation mechanisms were overwhelmed, resulting in increased body temperature to as high as 39.2 °C [26]. In vitro results of our study showed that EEF of the JCQ-B transducer was lower than that of JC transducer, which was in line with the results of in vivo experiments, indicating that the treatment efficiency was improved by using this new transducer.

In regards to safety, the modified BFR morphology of the JCQ-B transducer made it possible to ablate the lesion close to the skin and the pectoralis major without damaging those parts, which can be shown in the in vitro results of temperature detection in both the near and far acoustic fields. In a previous study using an animal udder model, it was shown that because of thermal build up in the near field, ablated lesions were usually longer in the ultrasound propagation direction [27]. However, the in vivo results of our study demonstrated that the ablated lesion within the goat udder was almost the same in the direction parallel with and perpendicular to the ultrasonic propagation, with the length-width ratio close to one, indicating decreased risk of tissue damages in the acoustic pathway, especially in the near field. Since the interaction between the ultrasonic beam and breast tissue was complicated, further studies need to be conducted to reveal the underlying mechanism. The increased safety was not only depended on the change of BFR morphology, but also depended on the change of other transducer parameters. When compared with the JC transducer, the focal length of the JCB-Q transducer was shortened. This change resulted in larger skin area involvement within the acoustic pathway at the same tissue depth. When the same energy was given during ablation, the energy deposition per unit of skin area was decreased, which increased skin safety, as being proved by the in vivo experiments that intact breast skin observed after the JCQ-B transducer sonication with high power, while small skin damages occurred by the JC transducer sonication at the same power. Therefore, the improvement of safety was observed in both in vitro and in vivo models.

The limitation of this study was that the temperature rise in the near and far acoustic fields was detected by inserting thermocouples in the tissue. The existence of thermocouple, especially in near acoustic field, may interfere with the propagation of focused ultrasound and deposition of ultrasonic energy in focal region. In the future study, a noninvasive temperature measurement method should be found out and used to measure the temperature rise not only in the acoustic field but also in the focus.

5. Conclusion

To adapt to the breast anatomy and to overcome the limitations of previous breast HIFU ablation, a novel extracorporeal transducer for better application of HIFU on breast tumors was created. This preclinical study demonstrated improved safety and efficacy of new transducer for the treatment of breast tissue. For a better understanding and wider utilization of this transducer, clinical trials need to be designed and investigated the JCB-Q transducer in the treatment of breast tumors.

Disclosure statement

The authors report there are no competing interests to declare.

Data availability statement

The datasets generated or analyzed during the study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was partially supported by the [Chongqing Graduate Research Innovation Project] under Grant [CYS22375].