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Abstract Focused ultrasound ablation surgery (FUAS) is a minimally invasive treatment option that has been utilized in various tumors. However, its clinical advancement has been hindered by issues such as low safety and efficiency, single image guidance mode, and postoperative tumor residue. To address these limitations, this study aimed to develop a novel multi-functional gas-producing engineering bacteria biological targeting cooperative system. Pulse-focused ultrasound (PFUS) could adjust the ratio of thermal effect to non-thermal effect by adjusting the duty cycle, and improve the safety and effectiveness of treatment.The genetic modification of Escherichia coli (E.coli) involved the insertion of an acoustic reporter gene to encode gas vesicles (GVs), resulting in gas-producing E.coli (GVs-E.coli) capable of targeting tumor anoxia. GVs-E.coli colonized and proliferated within the tumor while the GVs facilitated ultrasound imaging and cooperative PFUS. Additionally, multifunctional cationic polyethyleneimine (PEI)-poly (lactic-co-glycolic acid) (PLGA) nanoparticles (PEI-PLGA/EPI/PFH@Fe3O4) containing superparamagnetic iron oxide (SPIO, Fe3O4), perfluorohexane (PFH), and epirubicin (EPI) were developed. These nanoparticles offered synergistic PFUS, supplementary chemotherapy, and multimodal imaging capabilities.GVs-E.coli effectively directed the PEI-PLGA/EPI/PFH@Fe3O4 to accumulate within the tumor target area by means of electrostatic adsorption, resulting in a synergistic therapeutic impact on tumor eradication.In conclusion, GVs-E.coli-mediated multi-functional nanoparticles can synergize with PFUS and chemotherapy to effectively treat tumors, overcoming the limitations of current FUAS therapy and improving safety and efficacy. This approach presents a promising new strategy for tumor therapy. Graphical Abstract

Focused ultrasound ablation surgery (FUAS) is a minimally invasive treatment option that has been utilized in various tumors. However, its clinical advancement has been hindered by issues such as low safety and efficiency, single image guidance mode, and postoperative tumor residue. To address these limitations, this study aimed to develop a novel multi-functional gas-producing engineering bacteria biological targeting cooperative system. Pulse-focused ultrasound (PFUS) could adjust the ratio of thermal effect to non-thermal effect by adjusting the duty cycle, and improve the safety and effectiveness of treatment.The genetic modification of Escherichia coli (E.coli) involved the insertion of an acoustic reporter gene to encode gas vesicles (GVs), resulting in gas-producing E.coli (GVs-E.coli) capable of targeting tumor anoxia. GVs-E.coli colonized and proliferated within the tumor while the GVs facilitated ultrasound imaging and cooperative PFUS. Additionally, multifunctional cationic polyethyleneimine (PEI)-poly (lactic-co-glycolic acid) (PLGA) nanoparticles (PEI-PLGA/EPI/PFH@Fe3O4) containing superparamagnetic iron oxide (SPIO, Fe3O4), perfluorohexane (PFH), and epirubicin (EPI) were developed. These nanoparticles offered synergistic PFUS, supplementary chemotherapy, and multimodal imaging capabilities.GVs-E.coli effectively directed the PEI-PLGA/EPI/PFH@Fe3O4 to accumulate within the tumor target area by means of electrostatic adsorption, resulting in a synergistic therapeutic impact on tumor eradication.In conclusion, GVs-E.coli-mediated multi-functional nanoparticles can synergize with PFUS and chemotherapy to effectively treat tumors, overcoming the limitations of current FUAS therapy and improving safety and efficacy. This approach presents a promising new strategy for tumor therapy. [ABSTRACT FROM AUTHOR]

Objective To investigate the factors which may cause thermal injury of abdominal skin in patients with uterine fibroids (UFs) who underwent ultrasound-guided focused ultrasound ablation surgery (FUAS).Method A total of 123 patients were enrolled in the injury group. In contrast, 246 patients without thermal injury were assigned to the non-injury group. The relationship between patient and treatment parameters and injury were explored using univariate analysis and multiple logistic regression analyses. In addition, the factors influencing the degree of thermal injury were analyzed using Kruskal–Wallis H.Results (1) Abdominal scars (p = .007, OR = 2.187, 95% CI: 1.242–3.849), abdominal wall thickness (p

Background: A referenced MRI‐based classification associated with focused ultrasound ablation surgery (FUAS) outcomes is lacking in adenomyosis. Purpose: To identify an MRI‐based classification system for informing the FUAS outcomes. Study Type: Retrospective. Population: Patients with FUAS for adenomyosis, were divided into a training set (N = 643; 355 with post‐FUAS gonadotropin‐releasing hormone/levonorgestrel, 288 without post‐FUAS therapy) and an external validation set (N = 135; all without post‐FUAS therapy). Field Strength/Sequence: 1.5 T, turbo spin‐echo T2‐weighted imaging and single‐shot echo‐planar diffusion‐weighted imaging sequences. Assessment: Five MRI‐based adenomyosis classifications: classification 1 (C1) (diffuse, focal, and mild), C2 (intrinsic, extrinsic, intramural, and indeterminate), C3 (internal, adenomyomas, and external), C4 (six subtypes on areas [internal or external] and volumes [<1/3 or ≥2/3]), and C5 (internal [asymmetric or symmetric], external, intramural, full thickness [asymmetric or symmetric]) for FUAS outcomes (symptom relief and recurrence). Statistical Tests: The optimal classification was significantly associated with the most subtypes of FUAS outcomes. Relating to the timing of recurrence was measured using Cox regression analysis and median recurrence time was estimated by a Kaplan–Meier curve. A P value <0.05 was considered statistically significant. Results: Dysmenorrhea relief and recurrence were only associated with C2 in training patients undergoing FUAS alone. Compared with other subtypes, the extrinsic subtype of C2 was significantly associated with dysmenorrhea recurrence in the FUAS group. Besides, the median dysmenorrhea recurrence time of extrinsic subtype was significantly shorter than that of other subtypes (42.0 months vs. 50.3 months). In the validation cohort, C2 was confirmed as the optimal system and its extrinsic subtype was confirmed to have a significantly shorter dysmenorrhea recurrence time than other subtypes. Data Conclusion: Classification 2 can inform dysmenorrhea relief and recurrence in patients with adenomyosis undergoing FAUS only. Itsextrinsic subtype was associated with an earlier onset of dysmenorrhea recurrence after treatment. Evidence Level: 3 Technical Efficacy: Stage 5 [ABSTRACT FROM AUTHOR]

Objective: To explore the feasibility and safety of focused ultrasound ablation surgery for uterine fibroids under daytime surgical mode. Methods: Patients with uterine fibroids admitted to our hospital from January 2020 to December 2022 were selected as the research subjects. Based on the informed consent of the patients, they were randomly divided into observation group A, observation group B, and control group using a random number table method. Each group had 25 cases. The control group was treated with laparoscopic myomectomy, while the observation group A was treated with conventional hospitalization mode focused ultrasound ablation surgery, while the observation group B was treated with daytime surgery mode. Compare the treatment effectiveness of three groups of patients for uterine fibroids, including surgical time, hospital stay, postoperative VAS score, postoperative autonomous activity time, and treatment cost. Compare the incidence of postoperative adverse reactions among the three groups of patients. Finally, conduct outpatient follow-up at 3 months after surgery for all patients, evaluate the symptoms of uterine fibroids through symptom severity (SSS) score, and measure the volume of uterine fibroids through MRI imaging examination, Evaluate the quality of life of two groups of patients using the Comprehensive Quality of Life Assessment Questionnaire 74 (GQOLI-74). Results: The total effective rate of the control group was 100.00%, the observation group A was 96.00%, and the observation group B was 96.00%. There was no difference in the total effective rate among the three groups (P>0.05); There was no difference in surgical time between the three groups of patients (P>0.05). The hospitalization time, postoperative VAS score, postoperative autonomous activity time, and treatment cost of observation group B and observation group A were lower than those of the control group, and the hospitalization time and treatment cost of observation group B were lower than those of observation group A (P<0.05); The incidence of postoperative adverse reactions in Group A and Group B was lower than that in the control group (P<0.05), and there was no difference between Group A and Group B (P>0.05); There was no difference in preoperative SSS score, uterine fibroid volume, and GQOLI-74 dimension average score among the three groups of patients (P>0.05). After surgery, the SSS score and uterine fibroid volume of the three groups of patients decreased, while the GQOLI-74 dimension average score increased (P<0.05). However, there was no difference between the three groups of patients (P>0.05). Conclusion: Focused ultrasound ablation surgery has a significant therapeutic effect on uterine fibroids, and its therapeutic effect is not significantly different from laparoscopic myomectomy. However, it can reduce surgical trauma, shorten hospitalization time, and reduce postoperative pain for patients. Adopting daytime surgery mode focused ultrasound ablation surgery for uterine fibroids can further shorten patient hospitalization time, reduce surgical costs, and have high safety, There is no significant adverse effect on the prognosis of patients, and the feasibility is high. [ABSTRACT FROM AUTHOR]

Objective: To investigate the factors which may cause thermal injury of abdominal skin in patients with uterine fibroids (UFs) who underwent ultrasound-guided focused ultrasound ablation surgery (FUAS). Method: A total of 123 patients were enrolled in the injury group. In contrast, 246 patients without thermal injury were assigned to the non-injury group. The relationship between patient and treatment parameters and injury were explored using univariate analysis and multiple logistic regression analyses. In addition, the factors influencing the degree of thermal injury were analyzed using Kruskal–Wallis H. Results: (1) Abdominal scars (p =.007, OR = 2.187, 95% CI: 1.242–3.849), abdominal wall thickness (p <.001, OR = 1.042, 95% CI: 1.019–1.067), fundus fibroids (p =.038, OR = 1.790, 95% CI: 1.033–3.100), UFs with hyperintense/mixed T2-weighted imaging (T2WI) signals (p =.022, OR = 1.843, 95% CI: 1.091–3.115), average sonication power (AP) (p =.025, OR = 1.021, 95% CI: 1.003–1.039), and treatment time (TT) (p <.001, OR = 1.017, 95% CI: 1.011–1.023) were independent risk factors for thermal injury, while treatment volume (TV) (p =.002, OR = 0.775, 95% CI: 0.661–0.909) was a protective factor for injury. (2) Four groups were subdivided according to the degree of thermal injury(Group A: without skin injury. Group B: with changed T2WI signal in the abdominal wall, Group C: mild skin injury, Group D: severe skin injury), comparison of each with every other showed that the abdominal wall in Groups A and D was thinner than Groups B and C, with statistically significant differences (PAB<0.05, PAC<0.01, PDC<0.05, PDB<0.05); Group A was slightly thicker than D, however, without statistical difference. The ratio of sonication time (ST) to TV in Group A was the lowest of all (PAB, PAC, PAD all < 0.05). And as the level of thermal injury rose, the ratio gradually increased, however, without statistical difference. Conclusions: Based on our limited results, the following conclusion was made. (1) Abdominal scars, abdominal wall thickness, fundus fibroids, UFs with T2WI hyperintense/mixed signals, AP and TT were independent risk factor. (2) Neither too thick nor too thin abdominal walls would be recommended, as both might increase the risk of skin injury. (3) Noticeably, the risk of skin injury might increase considerably when the ST was longer and the sonication area was more fixed. [ABSTRACT FROM AUTHOR]

AbstractObjective To investigate the histopathological findings and follow-up outcome of focused ultrasound ablation surgery (FUAS) treatment of multiple fibroadenomas (FA).Methods A total of 20 patients with 101 multiple FAs were enrolled. After one session FUAS ablation, 21 lesions (≥15.0 mm) were surgically removed within one week for histopathological analysis, including 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, H&E staining, nicotinamide adenine dinucleotide (NADH) -flavretin enzyme staining, Transmission electron microscope (TEM) and scanning electron microscope (SEM). The remaining 80 lesions were followed up at 3, 6 and 12 months after treatment.Results All ablation procedures were performed successfully. Pathologic findings showed that irreversible damage of FA was confirmed. TTC, H&E and NADH staining and TEM/SEM demonstrated tumor cell death and tumor structural destruction at the gross, cellular, and subcellular levels, respectively. The median shrinkage rate at 12 months post-FUAS was 66.4 (43.6, 89.5) %.Conclusion Histopathological analysis for FAs after FUAS treatment proved that FUAS could effectively induce irreversible coagulative necrosis of FA, and the tumor volume would gradually shrink in follow-up. FUAS was safe and effective to treat multiple FAs with good cosmesis.Key pointsThis study was the first study of detailed histopathological analysis for FAs after FUAS treatment.FUAS can effectively induce irreversible coagulative necrosis of fibroadenoma cells.FUAS ablation of multiple fibroadenomas is safe and effective.

Abstract Focused ultrasound ablation surgery (FUAS) is a novel therapy with a wide range of potential applications. However, synergists are crucial to the therapy process due to the ultrasonic energy's attenuation properties. As a result of the complex hypoxic environment in the tumor area and many factors, the existing synergists have limitations such as weak targeting, single imaging mode, and easy tumor recurrence after treatment. Because of the above deficiencies, this study intends to construct bio-targeted oxygen production probes consisting of Bifidobacterium that naturally target the hypoxia region of the tumor and multi-functional oxygen-producing nanoparticles equipped with IR780, perfluorohexane (PFH), CBP (carboplatin), and oxygen. The probes are expected to achieve targeted and synergistic FUAS therapy and dual-mode imaging to mediate tumor diagnosis and treatment. The oxygen and drugs carried in it are accurately released after FUAS stimulation, which is expected to alleviate tumor hypoxia, avoid tumor drug resistance, improve the effect of chemotherapy, and realize FUAS combined with chemotherapy antitumor therapy. This strategy is expected to make up for the deficiencies of existing synergists, improve the effectiveness and safety of treatment, and provide the foundation for future tumor therapy progress. Graphical Abstract

Objectives To investigate the relationship between preoperative CA125 and symptom recurrence in adenomyosis after ultrasound-guided high-intensity focused ultrasound ablation surgery (FUAS).Methods A total of 502 adenomyosis patients after FUAS in Affiliated Nanchong Central Hospital of North Sichuan Medical College from June 2017 to March 2021 were reviewed. Factors associated with symptom recurrence of adenomyosis were analyzed by binary logistic regression model. ROC was used to determine the optimal cutpoint. Magnitude of preoperative CA125 relating to timing of symptom recurrence was measured by cox regression and Kaplan-Meier (K-M) curves. Besides, multiple liner regression model was used to identify the impacting factors for preoperative CA125.Results Multiple binary logistic analysis showed preoperative CA125 was related to symptom recurrence (OR = 1.002, 95%: 1.000～1.004, p = 0.043). The ROC of preoperative CA125 for recurrence validated 35 U/ml had a high sensitivity (82.5%). Preoperative CA125 was related to timing of symptom recurrence (HR = 2.255, 95%: 1.387–3.667, p = 0.001). K-M curves showed medium recurrence time in preoperative CA125 level >35 U/ml group (38.5 months) was shorter than that in CA125 level ≤35 U/ml group (44.5 months) (p = 0.001). Multiple liner regression analyses showed uterus volume and adenomyotic lesions volume positively correlated to preoperative CA125 level, while age negatively correlated to preoperative CA125 level.Conclusion The higher level of preoperative CA125 was related to an earlier onset of symptom recurrence after FUAS.

Acoustic attenuation in the propagation path of focused ultrasound ablation surgery determines the energy loss toward the focal region and is critical to the consequent treatment outcomes. In situ non-invasive, reliable, and accurate measurement is challenging for multi-layered heterogeneous tissues within the focusing angle. A novel measurement approach is proposed and its performance is evaluated using ex vivo porcine tenderloin and bovine heart. A big boiling bubble (i.e., larger than a few millimeters in size) was produced at the focus as a strong reflector inside the tissue, and the echo amplitudes were used to determine the acoustic attenuation. Two models, acoustic ray and energy loss, were developed to derive the equivalent acoustic attenuation coefficient for a focused beam. The measured acoustic attenuation coefficients of ex vivo porcine tenderloin and bovine heart at 0.97 MHz and a thickness of 3 cm are 0.159 ± 0.002 and 0.250 ± 0.005 Np/cm, respectively, which are all within the scope of measured values in the literature. In addition, the echo amplitude is sensitive to the conditions of the propagation path, and the inverse acoustic attenuation coefficient of the silicone gel pad placed in front of the tissue sample was 0.807 ± 0.002 Np/cm, which is comparable to the measurement using the insertion substitution method, 0.766 ± 0.003 Np/cm. Our proposed approach could determine the tissue acoustic attenuation for focused ultrasound ablation surgery reliably and accurately in situ. The easy operating protocol may allow clinical translation and adoption for improved safety and efficacy. [ABSTRACT FROM AUTHOR]

Focused ultrasound ablation surgery (FUAS) is a novel therapy with a wide range of potential applications. However, synergists are crucial to the therapy process due to the ultrasonic energy's attenuation properties. As a result of the complex hypoxic environment in the tumor area and many factors, the existing synergists have limitations such as weak targeting, single imaging mode, and easy tumor recurrence after treatment. Because of the above deficiencies, this study intends to construct bio-targeted oxygen production probes consisting of Bifidobacterium that naturally target the hypoxia region of the tumor and multi-functional oxygen-producing nanoparticles equipped with IR780, perfluorohexane (PFH), CBP (carboplatin), and oxygen. The probes are expected to achieve targeted and synergistic FUAS therapy and dual-mode imaging to mediate tumor diagnosis and treatment. The oxygen and drugs carried in it are accurately released after FUAS stimulation, which is expected to alleviate tumor hypoxia, avoid tumor drug resistance, improve the effect of chemotherapy, and realize FUAS combined with chemotherapy antitumor therapy. This strategy is expected to make up for the deficiencies of existing synergists, improve the effectiveness and safety of treatment, and provide the foundation for future tumor therapy progress. [ABSTRACT FROM AUTHOR]

Introduction: Focused ultrasound ablation surgery (FUAS) has been emerging to treat a wide range of conditions non-invasively and effectively with promising therapeutic outcomes. The focusing capability of an ultrasound transducer (i.e., focus shift, beam distortion, and acoustic pressure at the focus) determines the ablation effects. However, the focus shift and focal beam distortion after ultrasound propagating through multi-layered heterogeneous viscoelastic biological tissues become significant and are found to deteriorate the performance of FUAS in clinics.Methods: To achieve an accurate and reliable focal field among patients with large variations in the anatomical structures and properties, a spherical cavity transducer with open ends and sub-wavelength focal size (Li et al., APL, 2013,102:204102) was applied here. Both experimental measurements and numerical simulations were performed to characterize the acoustic fields of the spherical cavity transducer in water, the multi-layered concentric cylindrical phantom, and the heterogeneous tissue model (an adult male pelvis enclosed by porcine skin, fat, and muscle) and then compared with those of a conventional concave transducer at the same electrical power output.Results: It is found that standing-wave focusing using the spherical cavity transducer results in much less focus shift (0.25λ vs. 1.67λ) along the transducer axis and focal beam distortion (−6 dB beam area of 0.71 mm2vs. 4.72 mm2 in water and 2.55 mm2vs. 17.30 mm2 in tissue) in the focal plane but higher pressure focusing gain (40.05 dB vs. 33.61 dB in tissue).Discussion: Such a highly accurate and reliable focal field is due to the excitation at an appropriate eigen-frequency of the spherical cavity with the varied media inside rather than the reverberation from the concave surface. Together with its sub-wavelength focal size, the spherical cavity transducer is technically advantageous in comparison to the concave one. The improved focusing capability would benefit ultrasound exposure for not only safer and more effective FUAS in clinics, but also broad acoustic applications.

To investigate the histopathological findings and follow-up outcome of focused ultrasound ablation surgery (FUAS) treatment of multiple fibroadenomas (FA). A total of 20 patients with 101 multiple FAs were enrolled. After one session FUAS ablation, 21 lesions (≥15.0 mm) were surgically removed within one week for histopathological analysis, including 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, H&E staining, nicotinamide adenine dinucleotide (NADH) -flavretin enzyme staining, Transmission electron microscope (TEM) and scanning electron microscope (SEM). The remaining 80 lesions were followed up at 3, 6 and 12 months after treatment. All ablation procedures were performed successfully. Pathologic findings showed that irreversible damage of FA was confirmed. TTC, H&E and NADH staining and TEM/SEM demonstrated tumor cell death and tumor structural destruction at the gross, cellular, and subcellular levels, respectively. The median shrinkage rate at 12 months post-FUAS was 66.4 (43.6, 89.5) %. Histopathological analysis for FAs after FUAS treatment proved that FUAS could effectively induce irreversible coagulative necrosis of FA, and the tumor volume would gradually shrink in follow-up. FUAS was safe and effective to treat multiple FAs with good cosmesis. This study was the first study of detailed histopathological analysis for FAs after FUAS treatment. FUAS can effectively induce irreversible coagulative necrosis of fibroadenoma cells. FUAS ablation of multiple fibroadenomas is safe and effective. [ABSTRACT FROM AUTHOR]

Focused ultrasonic ablation surgery (FUAS) for tumor treatment has emerged as an effective non-invasive therapeutic approach, but its widespread clinical utilization is limited by its low therapeutic efficiency caused by inadequate tumor targeting, single imaging modality, and possible tumor recurrence following surgery. Therefore, this study aimed to develop a biological targeting synergistic system consisting of genetically engineered bacteria and multi-functional nanoparticles to overcome these limitations. Escherichia coli was genetically modified to carry an acoustic reporter gene encoding the formation of gas vesicles (GVs) and then target the tumor hypoxic environment in mice. After E. coli producing GVs (GVs- E. coli) colonized the tumor target area, ultrasound imaging and collaborative FUAS were performed; multi-functional nanoparticles were then enriched in the tumor target area through electrostatic adsorption. Multi-functional cationic lipid nanoparticles containing IR780, perfluorohexane, and banoxantrone dihydrochloride (AQ4N) were coloaded in the tumor to realize targeted multimodal imaging and enhance the curative effect of FUAS. AQ4N was stimulated by the tumor hypoxic environment and synergistically cooperated with FUAS to kill tumor cells. In sum, synergistic tumor therapy involving multi-functional nanoparticles mediated by genetically engineered bacteria overcomes the limitations and improves the curative effect of existing FUAS. Inadequate tumor targeting, single image monitoring mode, and prone tumor recurrence following surgery remain significant challenges yet critical for tumor therapy. This study proposes a strategy for genetically engineered bacteria-mediated multifunctional nanoparticles for synergistic tumor therapy. The multifunctional genetically engineered biological targeting synergistic agent can accomplish tumor-targeting therapy, synergistic FUAS ablation, hypoxia-activated chemotherapy combined with FUAS ablation, and multiple-imaging guidance and monitoring all at the same time, thereby compensating for the shortcomings of FUAS treatment. This strategy could pave the way for the progress of tumor therapy. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: To evaluate the feasibility, safety, and effectiveness of Focused Ultrasound Ablation Surgery (FUAS) combined with ultrasound-guided suction curettage in the management of Cesarean Scar Pregnancy (CSP).Study Design: We retrospectively analyzed 52 patients with CSP from April, 2017, to December, 2019. All the patients received one session of FUAS, and suction curettage under ultrasound guidance was performed 1-3 days after FUAS. The intraoperative blood loss in suction curettage, duration of vaginal bleeding after curettage, reproductive outcomes, and adverse effects were recorded and analyzed.Results: All the 52 patients completed one session of FUAS combined with suction curettage without serious adverse effects. The mean intraoperative blood loss was 32.81 ± 53.83 mL. 47 (90.38 %) patients had a successful suction curettage with a blood loss of less than 80 mL. 5 (9.62 %) patients had an active bleeding of ≥80 mL; however, the bleeding was stopped effectively by Foley's urinary catheter and no evident bleeding presented when the catheter was removed 24 h later. The mean duration of vaginal bleeding was 7.88 ± 4.24 days. 48 (92.30 %) patients recovered with little vaginal bleeding after curettage. 4 (7.69 %) type III CSP patients experienced late-onset severe bleeding and required UAE or surgery. During 6-36 months of the follow-up period, 12 patients expressed reproductive plan, in which 4 patients delivered by cesarean section, 3 patients had an ongoing pregnancy and 1 patient had an abortion in the early pregnancy.Conclusions: FUAS combined with ultrasound-guided suction curettage is a safe and effective treatment strategy in the management of CSP type I and CSP type II and is particularly advantageous for CSP patients with reproductive requirements. However, further studies are warranted to determine the meticulous inclusion criteria for patients with type III CSP. [ABSTRACT FROM AUTHOR]