Ultrasound in Medicine and Biology最新文献

{"title":"Enhanced Antitumor Efficacy and Reduced Cardiotoxicity of Ultrasound-Mediated Doxorubicin Delivery by Microbubble-Liposome Complexes.","authors":"Mingyu He, Xucai Chen, Francois Yu, Bin Qin, Huizhu Wang, Linda Lavery, Flordeliza S Villanueva","doi":"10.1016/j.ultrasmedbio.2025.04.010","DOIUrl":"https://doi.org/10.1016/j.ultrasmedbio.2025.04.010","url":null,"abstract":"<p><strong>Objective: </strong>Doxorubicin (Dox) is standard of care for treatment of sarcomas, but cumulative dosing is often limited by cardiotoxicity. We hypothesized that ultrasound targeted microbubble (MB) cavitation (UTMC) of a liposomal doxorubicin (LDox) conjugated polymer microbubble complex (DoxLPX) would enhance tumor inhibition and limit Dox cardiotoxicity.</p><p><strong>Methods: </strong>DoxLPX was intravenously injected in MCA205 sarcoma-bearing mice and concurrent ultrasound was delivered to the tumor site (DoxLPX + UTMC). Other mice received equivalent dosages of free Dox, LDox, or LDox + MB co-administration with UTMC (LDox + MB + UTMC). Tumor size and cardiac function were serially imaged with ultrasound. Postmortem cardiac tissue was analyzed for apoptosis. Biodistribution of Dox was performed with bioluminescence imaging postmortem where Cy5.5 was used as a fluorescent Dox analog.</p><p><strong>Results: </strong>DoxLPX + UTMC showed increased drug concentration in the tumor, a significant slowdown in tumor growth and prolonged median survival time. LDox and DoxLPX formulations had reduced drug extravasation into the myocardium. LDox + MB + UTMC also demonstrated superior tumor growth inhibition compared to free Dox and LDox. Three weeks after treatment commenced, DoxLPX + UTMC group showed significantly better left ventricular function indices than the free Dox group, consistent with biodistribution findings. Concordantly, heart tissue showed normal architecture of cardiac myocytes and significantly less interstitial/perivascular fibrosis in the DoxLPX + UTMC group.</p><p><strong>Conclusions: </strong>DoxLPX formulation in conjunction with ultrasound provides a targeted drug delivery platform with superior anti-tumor efficacy and reduced cardiac toxicity compared with systemic administration of free Dox.</p>","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DEMAC-Net: A Dual-Encoder Multiattention Collaborative Network for Cervical Nerve Pathway and Adjacent Anatomical Structure Segmentation.","authors":"H Cui, J Duan, L Lin, Q Wu, W Guo, Q Zang, M Zhou, W Fang, Y Hu, Z Zou","doi":"10.1016/j.ultrasmedbio.2025.04.006","DOIUrl":"https://doi.org/10.1016/j.ultrasmedbio.2025.04.006","url":null,"abstract":"<p><strong>Objective: </strong>Currently, cervical anesthesia is performed using three main approaches: superficial cervical plexus block, deep cervical plexus block, and intermediate plexus nerve block. However, each technique carries inherent risks and demands significant clinical expertise. Ultrasound imaging, known for its real-time visualization capabilities and accessibility, is widely used in both diagnostic and interventional procedures. Nevertheless, accurate segmentation of small and irregularly shaped structures such as the cervical and brachial plexuses remains challenging due to image noise, complex anatomical morphology, and limited annotated training data. This study introduces DEMAC-Net-a dual-encoder, multiattention collaborative network-to significantly improve the segmentation accuracy of these neural structures. By precisely identifying the cervical nerve pathway (CNP) and adjacent anatomical tissues, DEMAC-Net aims to assist clinicians, especially those less experienced, in effectively guiding anesthesia procedures and accurately identifying optimal needle insertion points. Consequently, this improvement is expected to enhance clinical safety, reduce procedural risks, and streamline decision-making efficiency during ultrasound-guided regional anesthesia.</p><p><strong>Methods: </strong>DEMAC-Net combines a dual-encoder architecture with the Spatial Understanding Convolution Kernel (SUCK) and the Spatial-Channel Attention Module (SCAM) to extract multi-scale features effectively. Additionally, a Global Attention Gate (GAG) and inter-layer fusion modules refine relevant features while suppressing noise. A novel dataset, Neck Ultrasound Dataset (NUSD), was introduced, containing 1,500 annotated ultrasound images across seven anatomical regions. Extensive experiments were conducted on both NUSD and the BUSI public dataset, comparing DEMAC-Net to state-of-the-art models using metrics such as Dice Similarity Coefficient (DSC) and Intersection over Union (IoU).</p><p><strong>Results: </strong>On the NUSD dataset, DEMAC-Net achieved a mean DSC of 93.3%, outperforming existing models. For external validation on the BUSI dataset, it demonstrated superior generalization, achieving a DSC of 87.2% and a mean IoU of 77.4%, surpassing other advanced methods. Notably, DEMAC-Net displayed consistent segmentation stability across all tested structures.</p><p><strong>Conclusion: </strong>The proposed DEMAC-Net significantly improves segmentation accuracy for small nerves and complex anatomical structures in ultrasound images, outperforming existing methods in terms of accuracy and computational efficiency. This framework holds great potential for enhancing ultrasound-guided procedures, such as peripheral nerve blocks, by providing more precise anatomical localization, ultimately improving clinical outcomes.</p>","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144080700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical Demonstration of In-Vivo Vein Occlusion by Mechanical HIFU Without Contrast Agent Injection: Paving the Way for the Non-Invasive Treatment of Varicose Veins.","authors":"A Ganeau, T Charrel, O Pichot, C Lafon","doi":"10.1016/j.ultrasmedbio.2025.04.004","DOIUrl":"https://doi.org/10.1016/j.ultrasmedbio.2025.04.004","url":null,"abstract":"<p><strong>Objective: </strong>High-intensity focused ultrasound (HIFU) is an emerging non-invasive treatment for various pathologies, including in the field of vascular medicine. Clinical studies have demonstrated its efficacy for vascular occlusion through thermal effects. An interesting yet early-stage alternative is mechanical HIFU, where occlusion is achieved by cavitation initiated by the injection of microbubble contrast agents. Our study aims to demonstrate the feasibility of an innovative ultrasound-guided mechanical HIFU device for non-invasive in-vivo vein occlusion by cavitation without microbubble contrast agents.</p><p><strong>Methods: </strong>A four piezoelectric ceramic device was developed and acoustically characterized. Erosion efficiency by cavitation was assessed on agar phantom models with cylindrical channels created to mimic veins. A preclinical feasibility demonstration was carried out in-vivo on a sheep model, targeting a collateral saphenous vein in the hind limb. Vein occlusion was investigated using ultrasound imaging during a 7-day follow-up and at the cellular level by histological analysis.</p><p><strong>Results: </strong>A maximum negative pressure of -23 MPa was measured at the focal point of dimension 1.27 mm³ at -6 dB . In agar phantom models, a centrally applied HIFU treatment was sufficient to erode small veins, while an application at multiple points was needed for larger veins. In vivo, cavitation was triggered in a small-diameter vein, causing occlusion and preventing blood flow. Histology confirmed vein wall damage and occlusion.</p><p><strong>Conclusion: </strong>Vein occlusion was successfully achieved in-vivo by cavitation using mechanical HIFU without microbubble contrast agents. This approach holds real potential for the non-invasive treatment of varicose veins, without the limitations of current techniques.</p>","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intra- and Peritumoral Radiomics Based on Ultrasound Images for Preoperative Differentiation of Follicular Thyroid Adenoma, Carcinoma, and Follicular Tumor With Uncertain Malignant Potential.","authors":"Ying Fu, Fang Mei, Liting Shi, Yihan Ma, Hainan Liang, Lei Huang, Rao Fu, Ligang Cui","doi":"10.1016/j.ultrasmedbio.2025.04.005","DOIUrl":"https://doi.org/10.1016/j.ultrasmedbio.2025.04.005","url":null,"abstract":"<p><strong>Objective: </strong>Differentiating between follicular thyroid adenoma (FTA), carcinoma (FTC), and follicular tumor with uncertain malignant potential (FT-UMP) remains challenging due to their overlapping ultrasound characteristics. This retrospective study aimed to enhance preoperative diagnostic accuracy by utilizing intra- and peritumoral radiomics based on ultrasound images.</p><p><strong>Methods: </strong>We collected post-thyroidectomy ultrasound images from 774 patients diagnosed with FTA (n = 429), FTC (n = 158), or FT-UMP (n = 187) between January 2018 and December 2023. Six peritumoral regions were expanded by 5%-30% in 5% increments, with the segment-anything model utilizing prompt learning to detect the field of view and constrain the expanded boundaries. A stepwise classification strategy addressing three tasks was implemented: distinguishing FTA from the other types (task 1), differentiating FTC from FT-UMP (task 2), and classifying all three tumors. Diagnostic models were developed by combining radiomic features from tumor and peritumoral regions with clinical characteristics.</p><p><strong>Results: </strong>Clinical characteristics combined with intratumoral and 5% peritumoral radiomic features performed best across all tasks (Test set: area under the curves, 0.93 for task 1 and 0.90 for task 2; diagnostic accuracy, 79.9%). The DeLong test indicated that all peritumoral radiomics significantly improved intratumoral radiomics performance and clinical characteristics (p < 0.04). The 5% peritumoral regions showed the best performance, though not all results were significant (p = 0.01-0.91).</p><p><strong>Conclusion: </strong>Ultrasound-based intratumoral and peritumoral radiomics can significantly enhance preoperative diagnostic accuracy for FTA, FTC, and FT-UMP, leading to improved treatment strategies and patient outcomes. Furthermore, the 5% peritumoral area may indicate regions of potential tumor invasion requiring further investigation.</p>","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Twin Peak Method for Estimating Tissue Viscoelasticity Using Shear Wave Elastography.","authors":"Shuvrodeb Adhikary, Matthew W Urban, Murthy N Guddati","doi":"10.1016/j.ultrasmedbio.2025.03.002","DOIUrl":"https://doi.org/10.1016/j.ultrasmedbio.2025.03.002","url":null,"abstract":"<p><p>Tissue viscoelasticity is becoming an increasingly useful biomarker beyond elasticity and can theoretically be estimated using shear wave elastography by inverting the propagation and attenuation characteristics of shear waves. Estimating viscosity is often more difficult than elasticity because attenuation, the main effect of viscosity, leads to poor signal-to-noise ratio of the shear wave motion. In the present work, we provide an alternative to existing methods of viscoelasticity estimation, based on peaks in the frequency-wavenumber (f-k) domain, which are considered more robust against noise compared with other features in the f-k domain. Specifically, the method minimizes the difference between simulated and measured versions of two sets of peaks (twin peaks) in the f-k domain, obtained first by traversing through each frequency and then by traversing through each wavenumber. The slopes and deviation of the twin peaks are sensitive to elasticity and viscosity, respectively, leading to the effectiveness of the proposed inversion algorithm for characterizing mechanical properties. This expected effectiveness is confirmed through in silico verification, followed by ex vivo validation and in vivo application, indicating that the proposed approach can be used effectively in accurately estimating viscoelasticity, thus potentially contributing to the development of enhanced biomarkers.</p>","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reliability of 3-D/4-D Ultrasound Contouring of Tongue Surface During Swallowing.","authors":"Brittany N Krekeler, Raele Donetha Loy, Nadeem Shaheen, Steven M Lulich, Payton Sheridan, Rodolfo E Peña-Chávez, Nadine P Connor, Nicole Rogus-Pulia","doi":"10.1016/j.ultrasmedbio.2025.03.016","DOIUrl":"https://doi.org/10.1016/j.ultrasmedbio.2025.03.016","url":null,"abstract":"<p><strong>Objective: </strong>The tongue has a critical role in swallowing, particularly related to bolus (i.e., food or liquid material) manipulation and propulsion through the oropharynx. Tongue contour (i.e., shape) is likely modulated based on the characteristics of the bolus material being swallowed, particularly pertaining to bolus containment prior to oral transport during swallowing. There are limited tools available to characterize tongue motion in a 3-D plane. The purpose of this preliminary study was to apply methodology for ultrasound imaging of the tongue to determine if lingual movement and contour can be reliably quantified during swallowing tasks.</p><p><strong>Methods: </strong>Lingual 3-D/4-D ultrasound data of tongue movement during swallowing were collected from 8 young, healthy participants (4 male, 4 female) using a convenience sample. Participants were presented with 4 different bolus thicknesses, each repeated 5 times (20 swallows total). In this report, only liquid bolus presentations were analyzed using an open-source WASL toolbox (WASL 10.3.6) for MATLAB. Reliability was measured from 8 frames per swallow, and root mean square was used to quantify inter- and intra-rater reliability.</p><p><strong>Results: </strong>The preliminary findings showed that reliable tongue surface contouring using 3-D/4-D ultrasound is possible during swallowing. The average inter- and intra-rater reliability, using root mean square, was 0.15-0.16 for liquid bolus swallows (0 = perfect agreement), indicating that these methods were highly reliable across and within raters.</p><p><strong>Conclusion: </strong>Lingual 3-D/4-D ultrasound can provide information about lingual movements in the 3-D plane. Our results demonstrate that tongue surface contouring during swallowing using 3-D/4-D ultrasound is reliable within and across raters. The work presented here lays the foundation for future work by establishing a method for tongue contour analysis during swallowing.</p>","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Full-Waveform Inversion With Low-frequency Extrapolation Based on Sparse Deconvolution for Ultrasound Computed Tomography.","authors":"Nuomin Zhang, Yang Xiao, Yu Yuan, Xudong Yang, Yi Shen","doi":"10.1016/j.ultrasmedbio.2025.04.003","DOIUrl":"https://doi.org/10.1016/j.ultrasmedbio.2025.04.003","url":null,"abstract":"<p><strong>Objective: </strong>In ultrasound computed tomography (USCT), full-waveform inversion (FWI) is a promising algorithm for high-resolution sound-speed reconstruction. When implementing FWI in practical imaging systems, insufficient high-quality, low-frequency information often leads to cycle skipping, which subsequently degrades convergence and accuracy. To address this problem, this paper proposes a modified FWI algorithm.</p><p><strong>Methods: </strong>Our approach incorporated low-frequency extrapolation for seismic imaging applications, capitalizing on the inherent sparsity of time-domain impulse response functions. Through a deconvolution-based framework, we enabled robust impulse response function estimation that facilitated the spectral extension of band-limited measurements. The extrapolated low-frequency components, while representing an approximate recovery rather than exact reconstruction of unmeasured frequencies, demonstrated sufficient fidelity for practical implementation in multi-frequency inversion workflows.</p><p><strong>Results: </strong>Numerical and experimental studies have demonstrated the efficacy of extrapolated low-frequency components in mitigating cycle-skipping artifacts. Compared with conventional low-pass filtering, the proposed method reduced the sound-speed reconstruction root mean square error from 34.47 m/s to 6.47 m/s. Phantom experiments confirmed the robustness of our method, demonstrating root mean square error reduction from 16.57 m/s (standard filtering) to 5.98 m/s (our method).</p><p><strong>Conclusion: </strong>This work relaxes the restriction of FWI in transducer frequency, potentially making FWI more compatible with high-frequency imaging modalities.</p>","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prediction of Hoarseness Risk After Microwave Ablation for Thyroid Nodules: A Visual Three-Zone Method Combined With a Nomogram.","authors":"Cai Hu, Huahui Liu, Yi Zhang, Shuxian Xu, Shuang Liang, Jing Yang, Qiqi Liu, Erjiao Xu","doi":"10.1016/j.ultrasmedbio.2025.04.001","DOIUrl":"https://doi.org/10.1016/j.ultrasmedbio.2025.04.001","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to analyze the risk factors that cause hoarseness after microwave ablation (MWA) and establish a visual zoning approach combined with a nomogram to predict the risk of hoarseness after MWA.</p><p><strong>Methods: </strong>Retrospective analysis of the images and clinical data of patients with thyroid nodules who underwent MWA was carried out from January 2021 to September 2024. Patients were divided into benign thyroid nodule and papillary thyroid cancer (PTC) groups. Parameters related to hoarseness were analyzed, including age, sex, multifocality, glandular thickness, nodule components, ablation power, nodule location, maximum nodule diameter and nodule distance from the thyroid capsule and tracheoesophageal groove, as well as a new \"three-zone method.\" Three different prediction models and a nomogram were constructed to predict the risk of hoarseness.</p><p><strong>Results: </strong>A total of 446 patients (126 males and 320 females; median age 44 years) with a total of 542 nodules were included in this study. The overall incidence rate of hoarseness after MWA was 2.9% (13/446), while it was 2.2% (5/223) in the benign nodule group and 3.6% (8/223) in the PTC group. Multivariate analysis showed that away from anterior capsule distance, close to tracheoesophageal groove distance and location in zone 3 were risk factors of hoarseness after MWA for PTC nodules. The above variables and outcomes were visualized via nomogram (C-index = 0.910).</p><p><strong>Conclusion: </strong>This combined model with the \"three-zone method\" and established nomogram could be employed to predict the incidence of hoarseness after MWA for PTC.</p>","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep Learning in Echocardiography for Enhanced Detection of Left Ventricular Function and Wall Motion Abnormalities.","authors":"Manal Alhussein, Michelle Xiang Liu","doi":"10.1016/j.ultrasmedbio.2025.03.015","DOIUrl":"https://doi.org/10.1016/j.ultrasmedbio.2025.03.015","url":null,"abstract":"<p><p>Cardiovascular diseases (CVDs) remain a leading cause of mortality worldwide, underscoring the need for advancements in diagnostic methodologies to improve early detection and treatment outcomes. This systematic review examines the integration of advanced deep learning (DL) techniques in echocardiography for detecting cardiovascular abnormalities, adhering to PRISMA 2020 guidelines. Through a comprehensive search across databases like IEEE Xplore, PubMed, and Web of Science, 29 studies were identified and analyzed, focusing on deep convolutional neural networks (DCNNs) and their role in enhancing the diagnostic precision of echocardiographic assessments. The findings highlight DL's capability to improve the accuracy and reproducibility of detecting and classifying echocardiographic data, particularly in measuring left ventricular function and identifying wall motion abnormalities. Despite these advancements, challenges such as data diversity, image quality, and the computational demands of DL models hinder their broader clinical adoption. In conclusion, DL offers significant potential to enhance the diagnostic capabilities of echocardiography. However, successful clinical implementation requires addressing issues related to data quality, computational demands, and system integration.</p>","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Possible Association of Nrf2/ARE and NFκB Response to Osteoblast Function in Spheroid Culture Induced by Low-Intensity Pulsed Ultrasound (LIPUS).","authors":"Yusuke Kubo, Anna Theresa Tangarife Bodensiek, Sebastian Lippross, Marek Weiler, Nina Reinhardt, Matias de la Fuente Klein, Matthias Gatz, Ulf Krister Hofmann, Fabian Kießling, Vera Jankowski, Jaana-Sophia Kern, Marta Rizk, Elizabeth Rosado Balmayor, Anna Bock, Michael Wolf, Thomas Pufe, Mersedeh Tohidnezhad","doi":"10.1016/j.ultrasmedbio.2025.03.013","DOIUrl":"https://doi.org/10.1016/j.ultrasmedbio.2025.03.013","url":null,"abstract":"<p><strong>Objective: </strong>NFκB negatively affects bone metabolism through inflammatory pathways, whereas Nrf2 benefits it by regulating antioxidant/detoxifying enzymes through antioxidant response element (ARE) activity. We investigated whether low-intensity pulsed ultrasound (LIPUS) enhances osteogenic differentiation in 3D culture and whether it affects osteoblastic differentiation-associated markers such as calcium and alkaline phosphatase (ALP), and the regulation of NFκB and/or ARE.</p><p><strong>Methods: </strong>Murine MC3T3-E1 preosteoblasts were used to produce 3D-spheroids, which were treated with LIPUS. Time-dependent morphological change of spheroids was evaluated by microscopy, histology, and micro-CT. To analyze changes in ARE levels, a combination of LIPUS with an optimal concentration and timing of the Nrf2-inducer sulforaphane was applied. Osteoblast differentiation and mineralization were achieved through stimulation with differentiation medium for 21-28 days, during which LIPUS was used every day at 24-hour intervals. Differentiation was evaluated using calcium and ALP assay. Finally, cells were transduced with SIN-lenti-NFκB/SIN-lenti-ARE construct, and the effects of single-shot LIPUS on NFκB and ARE were evaluated using Nano-Glo® Luciferase Assay.</p><p><strong>Results: </strong>Morphologically, in LIPUS group, shrinkage behaviour, which may correlate with cell differentiation, was observed to be more pronounced. NFκB activity with LIPUS was significantly lower than without treatment, whereas ARE activity showed significant increase only immediately after LIPUS treatment. Conversely, LIPUS enhanced ARE activity in combination with sulforaphane administration. After 28 days, the calcium content and ALP activity of LIPUS-treated spheroids increased significantly.</p><p><strong>Conclusion: </strong>This study suggests that LIPUS may have NFκB-downregulating, limited ARE-raising effects in combination with sulforaphane, and elevating osteoblast mineralization three-dimensionally. Thus, LIPUS could be useful for treating fractures in conditions of oxidative stress and hyper-inflammation.</p>","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144037727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}