Journal

Ultrasound in Medicine & Biology

Papers (23)

Efficacy and Safety of Focused Ultrasound Treatment for High-risk Human Papillomavirus Infection-related Cervical Intraepithelial Neoplasia Grade 2 in Nulligravidae Women: A Retrospective Study

This retrospective study aimed to investigate the efficacy and safety of focused ultrasound (FU) treatment for high-risk human papillomavirus (HR-HPV) infection-related cervical intraepithelial neoplasia grade 2 (CIN2) in nulligravidae under 35 y old, while also assessing pregnancy outcomes post-treatment. Nulligravid patients aged 18-35 y with histologically confirmed CIN2 and HR-HPV infection were included in the study. We collected demographics, pertinent medical history, HPV genotypes and cervical length at baseline. Follow-up evaluations were conducted at 6- and 12-mo intervals post-treatment to assess histopathological response, HPV infection clearance and adverse events related to treatment. A total of 31 eligible patients were recruited and underwent FU treatment. At the 6-mo follow-up, complete pathologic response was observed in 22 out of 31 patients (70.96%), while partial response was seen in eight out of 31 patients (25.80%). The average duration from pathological diagnosis to achieving either a complete response or partial response after treatment was 214.36 ± 24.31 (186-270) d. The baseline remission rate for HPV was 35.48% at 6 mo, increasing to 71.49% at 12 mo. Moderate lower abdominal pain and increased vaginal discharge were the most frequent adverse events. Among the patients desiring pregnancy, the successful pregnancy rate was 57.14%, resulting in eight deliveries. FU demonstrated a favorable safety profile and efficacy in nulliparous females under 35 y old with CIN2, and its benefits for fertility warrant further investigation.

The Impact of HIFU Ablation on the Histopathological Features of Locally Recurrent Fibroids Tissue Post-HIFU Treatment

To evaluate the impact of high-intensity focused ultrasound (HIFU) ablation on the histopathological features of locally recurrent fibroids tissue. Patients who underwent transabdominal hysterectomy or myomectomy for uterine fibroids from January 1, 2021 to July 1, 2023 at a teaching hospital in China were enrolled in this prospective study. The patients who underwent surgery for local recurrence of uterine fibroids after HIFU ablation were categorized as the HIFU group, and patients who had not undergone HIFU ablation for uterine fibroids were the control group. Hematoxylin-eosin (HE) staining, Masson staining, and immunohistochemical staining were performed to analyze the counts of smooth muscle cells (SMCs), collagen content, microvascular count, and the expression levels of estrogen receptor (ER) and progesterone receptor (PR) in the fibroid tissue specimens. The mean SMC counts in the HIFU and control groups were 337.68/field and 328.52/field respectively. The mean collagen content in the HIFU group and control group were 46.06% and 41.69% respectively. The mean microvessel counts in the HIFU group and control group were 13.66/field and 14.08/field respectively. The mean ER scores in the HIFU and control groups were 6.9 and 7.47 respectively, and the mean PR scores were 7.3 and 7.56 respectively. Overall, there were no significant differences in the SMC counts, collagen content, microvascular counts, and the ER and PR expression levels between the HIFU group and control group (p > 0.05). HIFU ablation has no effect on the pathological characteristics of local recurrent fibroid tissue, and is an ideal non-invasive treatment option.

Evaluating the Effects of Water Balloons on High-Intensity Focused Ultrasound for Treating Uterine Fibroids

In the treatment of uterine fibroids with ultrasound-guided high-intensity focused ultrasound (HIFU), water balloons are considered to be a valuable aid for improving safety and efficiency. However, the water balloons worsen the pathway for acoustic transmission, causing degraded performance both in ultrasound therapy and in ultrasound imaging. This study was aimed at establishing a protocol to evaluate the effects of the water balloon. Simulations and experiments were carefully conducted to quantitatively investigate the effects of water ballons on the efficiency of HIFU energy delivery and on the quality of ultrasound guiding images. More specifically, HIFU-induced temperature increases in the focal region, together with spatial resolution, contrast and signal-to-noise ratio in the ultrasound guiding images, were compared under the conditions with and without the water balloon. Experiment results revealed that the use of water balloons led to decreases in temperature up to 10ºC within the focal region in some specific situations, but the quality of the guiding images was relatively less affected. The study provided knowledge on what influence the water balloon could have in ultrasound-guided HIFU treatment; it also established a practical and standardized evaluation scheme for further optimizing the water balloon, for example, its material and internal liquid compositions. This study can potentially help improve the efficiency and safety of treating uterine fibroids with ultrasound-guided HIFU systems.

Ultrasound Microbubble-Mediated VHL Regulates the Biological Behavior of Ovarian Cancer Cells

According to the literature, the von Hippel-Lindau (VHL) gene has a certain correlation with ovarian cancer. In this study, we investigated the effect and mechanism of ultrasound microbubble-mediated VHL on the biological function of ovarian cancer cells. Non-targeting lipid microbubbles and targeted lipid microbubbles were prepared. OVCAR-3 cells were treated with VHL mediated by ultrasound and microbubbles alone or together. Expressions of VHL, Akt, epithelial-mesenchymal-transition-related proteins and apoptosis-related proteins were detected by Western blot and quantitative real-time polymerase chain reaction as needed. The effect of ultrasound microbubble-mediated VHL on the proliferation, apoptosis, cell cycle, migration and invasion of OVCAR-3 cells was examined by Cell Counting Kit-8, flow cytometry, wound-healing assay and Transwell. Compared with other treatment methods, ultrasound microbubble mediation enhanced VHL expression in OVCAR-3 cells. Overexpression of liposome-mediated VHL inhibited the proliferation and migration; caused cell-cycle arrest; promoted apoptosis: downregulated the expressions of MMP2, MMP9, E-cadherin, Akt and Bcl-2; and upregulated the expressions of VHL and BCL2-associated X protein (BAX) in OVCAR-3 cells. The effect of microbubble-treated VHL was similar to liposome-mediated regulation, while ultrasound treatment enhanced the effect of VHL on OVCAR-3 cells. More interestingly, ultrasound microbubble-mediated VHL had the most obvious regulatory effect on OVCAR-3 cells. Ultrasound microbubble technology increases the transfection efficiency of VHL into OVCAR-3 cells and enhances the effect of VHL gene on the biological function of OVCAR-3 cells.

Feasibility Study on Predicting the Energy and Time Requirements for Microwave Ablation of Uterine Fibroids Using Contrast-Enhanced Ultrasound Perfusion Parameters: A Cross-Sectional, Multicenter Study

To investigate the correlation between the quantitative perfusion parameters of contrast-enhanced ultrasound (CEUS) and the energy and time required per unit volume (EPV/TPV) for the treatment of uterine fibroids (UFs) via percutaneous microwave ablation (PMWA). This retrospective study included 263 patients from five centers with UFs who underwent PMWA treatment between December 2023 and October 2024. All patients underwent conventional ultrasound and CEUS prior to PMWA. Time-intensity curves for CEUS were recorded and the derived perfusion parameters - including maximum intensity (IMAX), rise time, time to peak and mean transit time - were obtained. Ablation power and duration were recorded during the procedure. Post-treatment CEUS was used to determine non-perfused volumes. The relationship between CEUS-derived quantitative perfusion parameters and EPV and TPV was evaluated. A total of 263 patients (272 UFs) were included, with 176 UFs achieving complete ablation and 96 achieving majority ablation. The mean age of the patients was 44.50 ± 5.58 y (range: 23-62 y). Logistic regression analysis revealed that the ablation rate was correlated with between IMAX and both EPV and TPV (all p < 0.001). Restricted cubic spline (RCS) analysis revealed a U-shaped nonlinear correlation between IMAX and both EPV and TPV (p IMAX of CEUS correlates non-linearly (U-shaped) with the energy and time requirements of PMWA for UFs. This finding supports the development of a clinically applicable ablation prediction model that provides a reliable pre-operative tool to optimize PMWA planning.

Evaluation of Pre-malignant Lesions of the Uterine Cervix by Shear Wave Elastography: A New Diagnostic Tool

The objective of the study was to evaluate the difference in the stiffness between a healthy cervix (no pre-invasive lesions [NPILs]) and a cervix with a pre-invasive lesion (PIL). In the PIL group, we determined whether there was a difference in stiffness between the cervix with persistent low-grade lesions (>2 y, LSIL-persistent) and that with high-grade lesions (HSILs). Evaluation was performed using 2-D shear-wave elastography (SWE) in the midsagittal-plane of the uterine cervix (UC) at 0.5 cm (cervical canal, anterior and posterior cervical lips). In this prospective observational study (consecutive series), we evaluated 96 non-pregnant women: a group with PIL (LSIL-persistent, 22 cases; HSIL, 26 cases) with indications for cervical conization (48 cases) and a group without UC pathology (NPIL, 48 cases). Although we did not observe statistically significant differences (SSDs) in epidemiological characteristics, we did find an SSD in the speed and stiffness between the PIL versus NPIL groups at all evaluated depths (speed: 4.1 m/s vs 3.0 m/s, stiffness: 58.6 and 34.5kPa in the PIL and NPIL groups, respectively, p < 0.001). An SSD in speed and stiffness (speed: 4.9 m/s vs. 3.2 m/s, and stiffness: 76.1 and 38.0 kPa) between the HSIL (26 cases) and LSIL-persistent (22 cases) groups, respectively, was also detected (p < 0.001). The area under the curve of speed differentiation between a cervix with HSILs and without lesions was 73.4% (95% confidence interval [CI]: 63.1-83.7), and the best cutoff of speed was 3.25 m/s (sensitivity = 62.5%, 95% CI: 47.3-76.0), with a specificity of 75.5% (95% CI: 60.4-87.1).

Differentiating Benign From Malignant Ovarian Masses With Solid Components: Diagnostic Performance of CEUS Combined With IOTA Simple Rules and O-RADS

This study aimed to apply the International Ovarian Tumor Analysis (IOTA) Simple Rules (SR), the Ovarian-Adnexal Reporting and Data System (O-RADS) and contrast-enhanced ultrasound (CEUS) in an identical cohort of Chinese patients and to analyze their performance in discrimination of ovarian masses with solid components. This was a two-center retrospective study that included a total of 94 ovarian lesions in 86 women enrolled from January 2018 to February 2023. The lesions were classified by using the IOTA terminology and CEUS was performed for the lesions exhibiting solid components on ultrasonography, IOTA SR and O-RADS were applied, and CEUS images were analyzed retrospectively. We assessed the time to wash-in, time to peak intensity (PI), PI compared to myometrium, and time to wash-out, and observed statistically significant differences between benign and malignant lesions in the first three parameters. CEUS characteristics were employed to determine CEUS scores for benign (score 0) and malignant (score 3) lesions. Subsequently, the lesions were reassessed based on the IOTA SR and O-RADS classifications and CEUS scores. The sensitivity, specificity, and area under the receiver-operating-characteristics curve (AUC) of the different models were also determined. Among the 94 ovarian lesions, 46 (48.9%) were benign and 48 (51.1%) were malignant. It was found that in the 60 lesions to which the SR could be applied, the sensitivity, specificity, and AUC was 0.900, 0.667, and 0.783, respectively. The sensitivity, specificity, and AUC of O-RADS was observed to be 1.000, 0.283 and 0.641, respectively. When SR and O-RADS were combined with CEUS, their sensitivity, specificity, and AUC values were increased to 0.917, 0.891, 0.904, and 0.958, 0.783, 0.871, respectively. IOTA SR and O-RADS exhibited relatively low specificity in differentiating malignant from benign ovarian lesions with the solid components, and their diagnostic performance can be significantly improved when combined with CEUS.

Evaluation of Uterine Fibroid Vascularity Using Contrast-Enhanced Ultrasound in Comparison with Contrast-Enhanced Magnetic Resonance Imaging

The aim of the work described here was to assess uterine fibroid vascularity using contrast-enhanced ultrasound (CEUS) as compared with magnetic resonance imaging (MRI). Forty women diagnosed with symptomatic uterine fibroids scheduled for uterine artery embolization (UAE) were enrolled in this institutional review board-approved study. Before UAE, participants underwent CEUS examination with an Aplio i800 scanner (Canon Medical Systems, Tustin, CA, USA) with curvilinear array (8C1). CEUS was performed using 2.0 mL of the ultrasound contrast agent Lumason (Bracco, Milan, Italy) administered intravenously. Digital CEUS clips were acquired and randomized offline, and fibroids were characterized as hyper- or hypovascular. MRI was used as reference standard for fibroid vascularity and compared with CEUS. Results were analyzed using McNemar's test. Forty participants were enrolled in the trial. One patient did not proceed with the UAE procedure and one patient refused pre-procedure MRI because of claustrophobia. Therefore, 38 participants underwent CEUS and MRI examinations before UAE. Hypervascular fibroids were seen on MRI and CEUS in 24 and 26 participants, respectively. Hypovascular fibroids were seen with MRI and CEUS in 14 and 12 participants, respectively. Fibroids characterized as hypovascular in two participants by MRI were characterized as hypervascular by CEUS. CEUS and MRI findings were similar in 36 of 38 participants, corresponding to an accuracy of 95% (p = 0.62). Contrast-enhanced ultrasound can accurately assess uterine fibroid vascularity, serving as a potential alternative to MRI in determination of the vascularity of uterine fibroids.

Accuracy of 3-D Surface Rendering of 2-D Ultrasound Images of the Uterus Using a Novel Software in Mapping Uterine Fibroids

Three-dimensional surface rendering of 2-D ultrasound images of the uterus in mapping uterine fibroids is a fast-evolving imaging technique that holds great potential for gynecology. The purpose of this study was to assess the accuracy of 3-D surface rendering of 2-D ultrasound images of the uterus using a new Fibroid Mapping Reviewer Application (FMRA) software for mapping uterine fibroids as compared with the pathological evaluation of uterine fibroids in pre-menopausal women undergoing hysterectomy. We enrolled women aged 35-55 y scheduled for hysterectomy for symptomatic fibroids at a tertiary care hospital from 2019 to 2021. Per pre-set guidelines, we recorded 2-D images and videos of the uterus with fibroids during the transvaginal ultrasound. The recordings were transferred through USB, loaded in the FMRA software and post-processed to generate a 3-D rendered uterus model. An experienced pathologist assessed and documented the gross examination details per a set protocol. We compared the pre-specified dimensions related to the size (L1, L2) and location (X, Y) of fibroids between the 3-D model and the pathologist's assessment of the hysterectomy specimen. A total of 25 fibroids in 25 women, the single largest per woman, were considered for analysis. The two methods had good correlation with respect to size (for L1, R² = 0.9723, and for L2, R² = 0.9784) and location (for X, R² = 0.9618, and for Y, R² = 0.9753). Inter-observer analysis revealed that measurements from two sonologists were reproducible (Cronbach's α = 0.9 for the L1, L2 and L3 dimensions of fibroids from the 3-D model). The FMRA is a novel tool for mapping fibroids. With its proven accuracy, it will be helpful in planning surgeries and during guided procedures for managing uterine fibroids.

Sonocavitation-Induced Mitochondrial Dysfunction via ROS-Mediated Apoptosis for Paclitaxel-Resistant Ovarian Cancer Therapy

To investigate whether sonocavitation, induced by low-intensity focused ultrasound combined with microbubbles, can overcome paclitaxel resistance in ovarian cancer by promoting apoptosis through reactive oxygen species (ROS)-mediated mitochondrial dysfunction. Paclitaxel-resistant ovarian cancer tissues and cell lines were compared with chemotherapy-sensitive counterparts for the expression of apoptosis-related proteins. Sonocavitation treatment was applied to resistant cells using optimized ultrasound parameters. Apoptosis, ROS production, mitochondrial morphology, oxygen consumption, mitochondrial membrane potential and mitochondrial membrane proteins were evaluated by flow cytometry, transmission electron microscopy, oxygen consumption assays, adenosine triphosphate (ATP) measurements, mitochondrial membrane potential assay kit staining and Western blotting. In vivo antitumor efficacy and biosafety were examined in paclitaxel-resistant xenograft mouse models, with tumor growth curves, survival analysis, and hematological/organ histology assessments. Paclitaxel-resistant ovarian cancer tissues exhibited elevated Bcl-2 and reduced Bax and Caspase-3, indicating impaired intrinsic apoptosis. Sonocavitation significantly increased apoptosis in resistant ovarian cancer cells and induced marked mitochondrial dysfunction, including reduced mitochondrial size, disrupted oxygen consumption, decreased ATP levels, collapse of mitochondrial membrane potential and destruction of mitochondrial membrane proteins. Cytochrome c release and activation of cleaved Caspase-3 confirmed mitochondrial-dependent apoptosis. In vivo, sonocavitation suppressed tumor growth and prolonged survival without causing systemic toxicity. ROS scavengers partially reversed these effects, confirming that ROS accumulation is a key mediator of the therapeutic mechanism. Sonocavitation induces apoptosis in paclitaxel-resistant ovarian cancer through ROS-mediated mitochondrial dysfunction and demonstrates effective tumor-suppressive activity with a favorable safety profile. These findings support sonocavitation as a promising adjuvant strategy to overcome chemoresistance and enhance ovarian cancer treatment outcomes.

Predictive Value of MRI Radiomics for the Efficacy of High-Intensity Focused Ultrasound (HIFU) Ablation in Uterine Fibroids: A Systematic Review and Meta-Analysis

High-Intensity Focused Ultrasound (HIFU) ablation has emerged as a non-invasive treatment option for uterine fibroids that preserves fertility and offers faster recovery. Pre-intervention prediction of HIFU efficacy can augment clinical decision-making and patient management. This systematic review and meta-analysis aims to evaluate the performance of MRI-based radiomics machine learning (ML) models in predicting the efficacy of HIFU ablation in uterine fibroids. Studies were retrieved by conducting a thorough literature search across databases including PubMed, Scopus, Embase, and Web of Science, up to June 2025. The quality of the included studies was assessed using the QUADAS-2 and METRICS tools. A meta-analysis of the radiomics models was conducted to pool sensitivity, specificity, and AUC using a bivariate random-effects model. A total of 13 studies were incorporated in the systematic review and meta-analysis. Meta-analysis of 608 patients from 7 internal and 6 external validation cohorts showed pooled AUC, sensitivity, and specificity of 0.84, 77%, and 78%, respectively. QUADAS-2 was notable for significant methodological biases in the index test and flow and timing domains. Across all studies, the mean METRICS score was 76.93%-with a range of 54.9%-90.3%-denoting good overall quality and performance in most domains but with notable gaps in the open science domain. MRI-based radiomics models show promise in predicting the effectiveness of HIFU ablation for uterine fibroids. However, limitations such as limited geographic diversity, inconsistent reporting standards, and poor open science practices hinder broader application. Therefore, future research should focus on standardizing imaging protocols, using multi-center designs with external validation, and integrating diverse data sources.

A Study on Automatic O-RADS Classification of Sonograms of Ovarian Adnexal Lesions Based on Deep Convolutional Neural Networks

This study explored a new method for automatic O-RADS classification of sonograms based on a deep convolutional neural network (DCNN). A development dataset (DD) of 2,455 2D grayscale sonograms of 870 ovarian adnexal lesions and an intertemporal validation dataset (IVD) of 426 sonograms of 280 lesions were collected and classified according to O-RADS v2022 (categories 2-5) by three senior sonographers. Classification results verified by a two-tailed z-test to be consistent with the O-RADS v2022 malignancy rate indicated the diagnostic performance was comparable to that of a previous study and were used for training; otherwise, the classification was repeated by two different sonographers. The DD was used to develop three DCNN models (ResNet34, DenseNet121, and ConvNeXt-Tiny) that employed transfer learning techniques. Model performance was assessed for accuracy, precision, and F1 score, among others. The optimal model was selected and validated over time using the IVD and to analyze whether the efficiency of O-RADS classification was improved with the assistance of this model for three sonographers with different years of experience. The proportion of malignant tumors in the DD and IVD in each O-RADS-defined risk category was verified using a two-tailed z-test. Malignant lesions (O-RADS categories 4 and 5) were diagnosed in the DD and IVD with sensitivities of 0.949 and 0.962 and specificities of 0.892 and 0.842, respectively. ResNet34, DenseNet121, and ConvNeXt-Tiny had overall accuracies of 0.737, 0.752, and 0.878, respectively, for sonogram prediction in the DD. The ConvNeXt-Tiny model's accuracy for sonogram prediction in the IVD was 0.859, with no significant difference between test sets. The modeling aid significantly reduced O-RADS classification time for three sonographers (Cohen's d = 5.75). ConvNeXt-Tiny showed robust and stable performance in classifying O-RADS 2-5, improving sonologists' classification efficacy.

A Novel Ultrasound-Based Radiomics Model for the Preoperative Prediction of Lymph Node Metastasis in Cervical Cancer

The purpose of this retrospective study was to establish a combined model based on ultrasound (US)-radiomics and clinical factors to predict preoperative lymph node metastasis (LNM) in cervical cancer (CC) patients non-invasively. A total of 131 CC patients who had cervical lesions found by transvaginal sonography (TVS) from the First Affiliated Hospital of Anhui Medical University (Hefei, China) were retrospectively analyzed. The clinical independent predictors were selected using univariate and multivariate logistic regression analysis. US-radiomics features were extracted from US images; after selecting the most significant features by univariate analysis, Spearman's correlation analysis, and the least absolute shrinkage and selection operator (LASSO) algorithm; four machine-learning classification algorithms were used to build the US-radiomics model. Fivefold cross-validation was then used to test the performance of the model and compare the ability of the clinical, US-radiomics and combined models to predict LNM in CC patients. Red blood cell, platelet and squamous cell carcinoma-associated antigen were independent clinical predictors of LNM (+) in CC patients. eXtreme Gradient Boosting performed the best among the four machine-learning classification algorithms. Fivefold cross-validation confirmed that eXtreme Gradient Boosting indeed performs the best, with average area under the curve values in the training and validation sets of 0.897 and 0.898. In the three prediction models, both the US-radiomics model and the combined model showed good predictive efficacy, with average area under the curve values in the training and validation sets of 0.897, 0.898 and 0.912, 0.905, respectively. US-radiomics features combined with clinical factors can preoperatively predict LNM in CC patients non-invasively.

Contrast-Enhanced Ultrasonography for Transabdominal and Transrectal Ultrasound in Staging Cervical Cancer: A Reliability Study

This retrospective study aimed to evaluate the consistency of transrectal contrast-enhanced ultrasonography (TR-CEUS) with post-operative pathology and the value of contrast-enhanced ultrasonography (CEUS) in staging surgically treated cervical cancer when combined with conventional ultrasonography (US). From October 2020 to March 2023, hospitalized patients with stage IB and II cervical cancer confirmed by total hysterectomy were consecutively enrolled. The standard images of US and CEUS by transabdominal (TA-US/CEUS) and transrectal (TR-US/CEUS) approaches and magnetic resonance imaging (MRI) were acquired, on which the size and stage of the tumors were evaluated, and the consistency of results with the pathological specimen was analyzed. Thirty-nine patients with cervical cancer were finally enrolled in this study. The results showed that CEUS significantly improved the reliability of TA-US in evaluating tumor diameter; the intraclass correlation coefficient (ICC) was from 0.672 to 0.735. TR-US indicated good reliability with or without the addition of CEUS (ICC = 0.796 and 0.780). In terms of tumor staging, CEUS improved the consistency of transabdominal (weighted κ values from 0.689 to 0.731) and transrectal staging of tumors (κ from 0.758 to 0.785), and the staging of TR-US combined with TR-CEUS had the highest consistency with post-operative results, similar to MRI (κ, respectively 0.785 and 0.789). CEUS can reflect the heterogeneity of the tumor. Heterogeneous enhancement and perfusion defects were more common in >2 cm cervical cancer (50%, 20/40 and 52.5%, 21/40), respectively, and perfusion defects were more common in moderately to poorly differentiated tumors (66.67%, 20/30). For stage IB and IIA cervical cancer, CEUS can aid in assessing the International Federation for Gynecology and Obstetrics staging of tumors alongside TA-US and TR-US. The combination of TR-US and TR-CEUS has shown good consistency with pathology in the staging of cervical cancer, comparable to that of MRI.

Publisher

Elsevier BV

ISSN

0301-5629