Comparison of Dose and Effectiveness of a Single-Session Ultrasound-Guided High-Intensity Focused Ultrasound Ablation of Uterine Fibroids With Different Sizes

PurposeThis study aimed to compare the dose and effectiveness of ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation of uterine fibroids with different sizes and explore the effect of uterine fibroid size on dose, which provided dose evaluation for clinicians in accordance with the size of uterine fibroids.Materials and MethodsA total of 1,000 patients with symptomatic uterine fibroids who received a single-session USgHIFU treatment were enrolled in this study. The size of fibroids was divided into seven groups: 3–4 cm, 4–5 cm, 5–6 cm, 6–7 cm, 7–8 cm, 8–9 cm, and 9–11 cm. The dose was expressed on the basis of the energy efficiency factor (EEF) as the energy required for ablation per unit volume of tissue, and the non-perfused volume ratio (NPVR) was used to assess the effect of HIFU ablation.ResultsThe median NPVR of 88.3% (IQR: 80.3%–94.8%) was obtained, and no significant difference was observed among the seven groups. The classification of T2-weighted image signal intensity fibroids in the 4–5 cm group was compared with that in the 6–7 cm and 8–9 cm groups, and the difference was significant (p < 0.05). However, the proportion of T2WI hyperintense signal fibroids had no significant difference among the seven groups (p > 0.05). The median EEF was 3.88 J/mm3, and a significant difference was observed among the seven groups of EEF (p < 0.05). The EEF of groups with a fibroid size less than 6 cm was more than double the EEF of groups with a fibroid size above 6 cm. In addition, the EEF of groups with a fibroid size of 4–5 cm and 3–4 cm was 3–4 times higher than those with a fibroid size above 7 cm (p < 0.05).ConclusionsA single-session HIFU ablation for uterine fibroids of 3–11 cm can obtain an NPVR of more than 80%. The EEF decreased with the increase of the size of uterine fibroids. A fibroid size of 6.5 cm was considered as a clinical meaningful point affecting EEF.

Alterations in Immune Response Profile of Tumor-Draining Lymph Nodes after High-Intensity Focused Ultrasound Ablation of Breast Cancer Patients

Previous studies have revealed that high-intensity focused ultrasound (HIFU) ablation can trigger an antitumor immune response. The aim of this study was to investigate immune response in tumor-draining lymph nodes (TDLNs) after HIFU treatment. Forty-eight female patients with biopsy-confirmed breast cancer were divided into a control group and an HIFU group. In the control group, 25 patients underwent modified radical mastectomy, but 23 patients in the HIFU group received HIFU ablation of primary cancer, followed by the same operation. Using HE and immunohistochemical staining, the immunologic reactivity pattern and immune cell profile were assessed in paraffin-embedded axillary lymph nodes (ALNs) in all patients. The results showed that ALNs presented more evident immune reactions in the HIFU group than in the control group (100% vs. 64%). Among the ALNs, 78.3% had mixed cellular and humoral immune response, whereas 36% in the control group showed cellular immune response. The numbers of CD3+, CD4+, NK cell, and activated CTLs with Fas ligand+, granzyme+ and perforin+ expression were significantly higher in the ALNs in the HIFU group. It was concluded that HIFU could stimulate potent immune response and significantly increase T cell, activated CTLs and NK cell populations in the TDLNs of breast cancer.

Neutrophil-mediated clinical nanodrug for treatment of residual tumor after focused ultrasound ablation

Background The risk of local recurrence after high-intensity focused ultrasound (HIFU) is relatively high, resulting in poor prognosis of malignant tumors. The combination of HIFU with traditional chemotherapy continues to have an unsatisfactory outcome because of off-site drug uptake. Results Herein, we propose a strategy of inflammation-tendency neutrophil-mediated clinical nanodrug targeted therapy for residual tumors after HIFU ablation. We selected neutrophils as carriers and PEGylated liposome doxorubicin (PLD) as a model chemotherapeutic nanodrug to form an innovative cell therapy drug (PLD@NEs). The produced PLD@NEs had a loading capacity of approximately 5 µg of PLD per 106 cells and maintained the natural characteristics of neutrophils. The targeting performance and therapeutic potential of PLD@NEs were evaluated using Hepa1-6 cells and a corresponding tumor-bearing mouse model. After HIFU ablation, PLD@NEs were recruited to the tumor site by inflammation (most in 4 h) and released PLD with inflammatory stimuli, leading to targeted and localized postoperative chemotherapy. Conclusions This effective integrated method fully leverages the advantages of HIFU, chemotherapy and neutrophils to attract more focus on the practice of improving existing clinical therapies. Graphical Abstract

Prediction of Clinical Outcome for High-Intensity Focused Ultrasound Ablation of Uterine Leiomyomas Using Multiparametric MRI Radiomics-Based Machine Leaning Model

ObjectivesThis study sought to develop a multiparametric MRI radiomics-based machine learning model for the preoperative prediction of clinical success for high-intensity-focused ultrasound (HIFU) ablation of uterine leiomyomas.MethodsOne hundred and thirty patients who received HIFU ablation therapy for uterine leiomyomas were enrolled in this retrospective study. Radiomics features were extracted from T2-weighted (T2WI) image and ADC map derived from diffusion-weighted imaging (DWI). Three feature selection algorithms including least absolute shrinkage and selection operator (LASSO), recursive feature elimination (RFE), and ReliefF algorithm were used to select radiomics features, respectively, which were fed into four machine learning classifiers including k-nearest neighbors (KNN), logistic regression (LR), random forest (RF), and support vector machine (SVM) for the construction of outcome prediction models before HIFU treatment. The performance, predication ability, and clinical usefulness of these models were verified and evaluated using receiver operating characteristics (ROC), calibration, and decision curve analyses.ResultsThe radiomics analysis provided an effective preoperative prediction for HIFU ablation of uterine leiomyomas. Using SVM with ReliefF algorithm, the multiparametric MRI radiomics model showed the favorable performance with average accuracy of 0.849, sensitivity of 0.814, specificity of 0.896, positive predictive value (PPV) of 0.903, negative predictive value (NPV) of 0.823, and the area under the ROC curve (AUC) of 0.887 (95% CI = 0.848–0.939) in fivefold cross-validation, followed by RF with ReliefF. Calibration and decision curve analyses confirmed the potential of model in predication ability and clinical usefulness.ConclusionsThe radiomics-based machine learning model can predict preoperatively HIFU ablation response for the patients with uterine leiomyomas and contribute to determining individual treatment strategies.

Feasibility of Magnetic Resonance-Guided High Intensity Focused Ultrasound Treatment Targeting Distinct Nodular Lesions in Neurofibromatosis Type 1

Background Patients with Neurofibromatosis Type 1 (NF1) and plexiform neurofibromas (PN) often have radiographically diagnosed distinct nodular lesions (DNL) which can cause pain and weakness. Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) can precisely and accurately deliver heat to thermally ablate target tissue. The aim of this study is to evaluate whole-body MRIs from patients with NF1 and DNL, applying volumetrics and a consistent treatment planning approach to determine the feasibility of MR-HIFU ablation of DNL. Methods A retrospective review of whole-body MRI scans from patients with NF1 and PN from CNH and NCI was performed. DNL are defined as lesions >3cm, distinct from PN and lacking the “central dot” feature. Criteria for MR-HIFU thermal ablation include target location 1-8cm from skin surface; >1cm from visible plexus, spinal canal, bladder, bowel, physis; and ability to ablate ≥50% of lesion volume. Lesions in skull and vertebral body were excluded. Results In 26 patients, 120 DNL were identified. The majority of DNL were located in an extremity (52.5%). Other sites included head/neck (7%), chest (13%), and abdomen/pelvis (28%). The pre-defined HIFU ablation criteria was not met for 47.5% of lesions (n=57). The main limitation was proximity to a vital structure or organ (79%). Complete and partial HIFU ablation was feasible for 25% and 27.5% of lesions, respectively. Conclusion Based on imaging review of lesion location, technical considerations and ability to target lesions, thermal ablation with MR-HIFU may be a feasible non-invasive alternative for symptom management in patients with NF1 and symptomatic DNL.

Neutrophil-Mediated Clinical Nanodrug for Treatment of Residual Tumor After Focused Ultrasound Ablation

Background: The risk of local recurrence of high intensity focused ultrasound (HIFU) is relatively high, resulting in poor prognosis of malignant tumors. Combination of HIFU with traditional chemotherapy still remains the unsatisfactory outcome because of off-site drug uptake.Results: Herein, we proposed the strategy of inflammation-tendency neutrophil-mediated clinical nanodrug targeting therapy for residual tumor of HIFU ablation. Neutrophils as a carrier, and PEGylated liposome doxorubicin (PLD) as a nanodrug model of chemotherapy, were selected to form an innovative cell therapy drug (PLD@NEs). The targeting performance and therapeutic potential of PLD@NEs were evaluated using hepa1-6 cells and corresponding tumor-bearing mouse model. After HIFU ablation, PLD@NEs were recruited to the tumor site by inflammation, and released PLD with inflammatory stimuli, leading to targeted and localized postoperative chemotherapy.Conclusion: This effective integration takes full use of the advantages of both HIFU, chemotherapy and neutrophil, attracting more focus on the practice of improving the existing clinical therapeutics.

An experiment of using the SonoVue ultrasound contrast agent for focused high-intensity ultrasound ablation of uterine fibroids

BACKGROUND: One of the modern methods of organ-saving non-invasive remote treatment of uterine fibroids is ablation of myomatous nodes with high-intensity focused ultrasound (HIFU). AIM: The aim of this study was to analyze changes in the parameters of ultrasonic ablation when using intraoperative control with the help of an ultrasound contrast agent. MATERIALS AND METHODS: In the period from 2016 to 2018, a total of 208 patients with symptomatic uterine myoma underwent HIFU ablation of myomatous nodes. The two groups of patients were compared: group I included 98 patients aged 36 to 52 years (mean age: 44.39 7.12 years) with intraoperative control with an ultrasound contrast agent (sulfur hexafluoride); group II consisted of 110 patients aged 20 to 55 years (mean age: 38.33 8.72 years), whose treatment was not controlled by the contrast agent. RESULTS: Using the Mann-Whitney test, we obtained statistically significant differences in the following parameters: the duration of ultrasound ablation was 215.28 70.57 min (from 70 to 390 min) in group I, and 610.84 56.26 min (from 290 to 1230 min) in group II (p 0.005); the average energy was 329.06 33.06 W in group I, and 293.68 64.51 W in group II (p 0.001); good tolerance of the operation was shown in 91% of cases in group I, and in 61.8% of cases in group II; satisfactory tolerance of the operation was shown in 7.7% of cases in group I, and in 37.3% of cases in group II (p 0.001). CONCLUSIONS: The data obtained indicate that the performance of HIFU ablation with the use of an ultrasonic contrast agent allowed halving the insonation time, while using submaximal and maximum ultrasound exposure powers with better tolerance of intervention by patients.