Magnetic Resonance Imaging-Based Classification Systems for Informing Better Outcomes of Adenomyosis After Ultrasound-Guided High-Intensity Focused Ultrasound Ablating Surgery.

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.

Factors associated with thermal injury of abdominal skin in focused ultrasound ablation of uterine fibroids.

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.

Comparing the effect of FUAS and myomectomy on the elasticity of myometrium around targeted uterine fibroid.

BACKGROUND: Focused ultrasound ablation surgery (FUAS) has been widely employed to treat patients with uterine fibroid (UF). This study aimed to estimate myometrial stiffness changes in patients who received FUAS for UFs or myomectomy (ME) and compare the recovery of surrounding myometrium between FUAS and ME groups. Our results may provide more evidence for guiding the proper conception timing in patients with UF. METHODS: This study enrolled 173 patients from May 2022 to August 2023. Shear wave elastography (SWE) was used to dynamically monitor myometrial elasticity changes in patients before and after surgery. Moreover, our study monitored and analyzed the stiffness changes in the targeted fibroid after FUAS, as well as in the myometrium around after FUAS or ME. RESULTS: The stiffness of the myometrium around the resected fibroid was significantly higher than at the preoperative level until 6 months. Conversely, the stiffness of the surrounding myometrium was only temporarily increased 1 day after FUAS. The comparison between FUAS and ME groups regarding the stiffness of the surrounding myometrium showed that nonsignificant differences were detected between the two groups before the treatment. The stiffness of the surrounding myometrium in the ME group was statistically significantly higher than that of the FUAS group 1 day as well as 1, 3, and 6 months after the treatment, respectively. CONCLUSION: The FUAS had less impact on the surrounding myometrium than the ME, which may be more conducive to the recovery of myometrial elasticity in patients with UF.

In vivo evaluation of focused ultrasound ablation surgery (FUAS)-induced coagulation using echo amplitudes of the therapeutic focused ultrasound transducer.

OBJECTIVE: Monitoring sensitivity of sonography in focused ultrasound ablation surgery (FUAS) is limited (no hyperechoes in ∼50% of successful coagulation in uterine fibroids). A more accurate and sensitive approach is required. METHOD: The echo amplitudes of the focused ultrasound (FUS) transducer in a testing mode (short pulse duration and low power) were found to correlate with the ex vivo coagulation. To further evaluate its coagulation prediction capabilities, in vivo experiments were carried out. The liver, kidney, and leg muscles of three adult goats were treated using clinical FUAS settings, and the echo amplitude of the FUS transducer and grayscale in sonography before and after FUAS were collected. On day 7, animals were sacrificed humanely, and the treated tissues were dissected to expose the lesion. Echo amplitude changes and lesion areas were analyzed statistically, as were the coagulation prediction metrics. RESULTS: The echo amplitude changes of the FUS transducer correlate well with the lesion areas in the liver (R = 0.682). Its prediction in accuracy (94.4% vs. 50%), sensitivity (92.9% vs. 35.7%), and negative prediction (80% vs. 30.8%) is better than sonography, but similar in specificity (80% vs. 100%) and positive prediction (100% vs. 100%). In addition, the correlation between tissue depth and the lesion area is not good (|R| < 0.2). Prediction performances in kidney and leg muscles are similar. CONCLUSION: The FUS echo amplitudes are sensitive to the tissue properties and their changes after FUAS. They are sensitive and reliable in evaluating and predicting FUAS outcomes.

US/PA/MR multimodal imaging-guided multifunctional genetically engineered bio-targeted synergistic agent for tumor therapy.

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.

Focused ultrasound ablation surgery for multiple breast fibroadenomas: pathological and follow-up results.

OBJECTIVE: 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.

Dual mode imaging guided multi-functional bio-targeted oxygen production probes for tumor therapy.

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.

Preoperative CA125 as a risk factor for symptom recurrence of adenomyosis after ultrasound-guided high-intensity focused ultrasound ablation surgery.

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.

In Situ Measurement of Acoustic Attenuation for Focused Ultrasound Ablation Surgery Using a Boiling Bubble at the Focus.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Genetically engineered bacteria-mediated multi-functional nanoparticles for synergistic tumor-targeting therapy.

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. STATEMENT OF SIGNIFICANCE: 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.

Focused Ultrasound Ablation Surgery combined with ultrasound-guided suction curettage in the treatment and management of Cesarean Scar Pregnancy.

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.

Effectiveness and safety of focused ultrasound ablation surgery compared with radiofrequency ablation in primary hepatocellular carcinoma treatment: a meta-analysis.

BACKGROUND: The effectiveness and safety of focused ultrasound ablation surgery (FUAS) for primary hepatocellular carcinoma (HCC) treatment has not been fully evaluated. This study analyzed the effectiveness and safety of FUAS compared to radiofrequency ablation (RFA). METHODS: Studies published before November 1, 2020, in the following databases were analyzed: PubMed, Embase, Cochrane Library, Web of Science, Wanfang Data, CqVip, China National Knowledge Infrastructure (CNKI), and Chinese Biomedical (CBM) database. All publications were reviewed independently by two authors. Both randomized controlled trials (RCTs) and cohort studies examining the effectiveness and safety of FUAS and RFA were considered. RCTs and cohort studies' methodological quality were evaluated using the Cochrane collaboration tool and the Newcastle-Ottawa Scale, respectively. RESULTS: A total of 6,597 records were identified, from which 3 cohort studies were selected for quantitative synthesis. All studies had relatively high methodological quality. The meta-analysis indicated that FUAS and RFA had comparable 3-month overall survival (OS) rates [risk ratio (RR): 0.99, 95% confidence interval (CI): 0.86 to 1.14], 6-month OS rates (RR: 1.03, 95% CI: 0.82 to 1.29), and 1-year OS rates (RR: 0.96, 95% CI: 0.84 to 1.11). Also, individual studies reported that the tumor response (reflected by tumor response and tumor ablation rate) and posttreatment complications were comparable between patients treated with FUAS and patients treated with RFA. Due to the limited number of studies reporting tumor response and posttreatment complications, further meta-analyses could not be conducted. DISCUSSION: FUAS and RFA were comparable in terms of effectiveness and safety in the treatment of primary HCC. However, current evidence is limited, and more prospective RCTs are warranted to confirm these findings.