Xavier Navy, Zhiyu Sheng, Kang Kim, John M Cormack
{"title":"Three-Dimensional Tissue Strain Measurement Using a Row-Column Array During Biaxial Testing of Excised Ventricular Porcine Myocardium.","authors":"Xavier Navy, Zhiyu Sheng, Kang Kim, John M Cormack","doi":"10.1016/j.ultrasmedbio.2025.05.007","DOIUrl":"https://doi.org/10.1016/j.ultrasmedbio.2025.05.007","url":null,"abstract":"<p><strong>Objective: </strong>To implement and validate a 3D volume imaging sequence and 3D strain estimation procedure for enhanced biaxial mechanical testing of excised ventricular myocardium.</p><p><strong>Methods: </strong>One specimen of right and one of left ventricular excised porcine myocardium were tested using dual-loading protocol quasistatic biaxial mechanical testing. During biaxial testing, volume ultrasound (US) images were acquired using a row-column addressed array probe using a synthetic aperture imaging sequence. Volume US images were used to compute tissue deformation using 3D correlation-based US speckle tracking. US-derived tissue strains were validated against repeated measurements using conventional optical camera imaging of the specimen surface deformation.</p><p><strong>Results: </strong>Speckle tracking yielded high-fidelity maps of tissue deformation in 3D throughout the entire sample volume. US-derived tissue strain is in good agreement with ground-truth camera-derived surface strain measurements (root mean square error is 1.6% strain).</p><p><strong>Conclusion: </strong>The 3D full-thickness strain measurement with US imaging is accurate and can enhance biomechanical insights from biaxial experimentation, especially in large tissues such as porcine and human myocardium where assumptions of plane stress and incompressibility may not apply.</p>","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295207","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}
Peter R Hoskins, Rebecca M Reynolds, Kathryn Hunt, Rosemary Townsend
{"title":"Umbilical Artery Wall Shear Stress and Control of the Feto-placental Circulation.","authors":"Peter R Hoskins, Rebecca M Reynolds, Kathryn Hunt, Rosemary Townsend","doi":"10.1016/j.ultrasmedbio.2025.05.012","DOIUrl":"https://doi.org/10.1016/j.ultrasmedbio.2025.05.012","url":null,"abstract":"<p><p>The aim of this paper is to review the area of wall shear stress (WSS) in umbilical arteries and to present a new theory for the short-term (seconds) control of placental resistance, which could be mediated by WSS. The endothelium senses changes in WSS, and a series of biological changes ensues with timescales of seconds to weeks. Wall shear stress mediates a control mechanism in which the arterial diameter changes in order to maintain WSS within a narrow range. Umbilical artery WSS has been estimated using a combination of ultrasound measurement of diameter and blood velocity (from maximum Doppler frequency shift), and computational fluid dynamics. The measurement of maximum blood velocity using commercial ultrasound systems is overestimated by typically 20%-40% in clinical ultrasound and 40%-60% in pre-clinical ultrasound. Measurements of WSS that use an estimate of maximum velocity from maximum Doppler frequency will also be overestimated by similar amounts. The overestimation of maximum velocity is due to geometric spectral broadening, which can be corrected at the time of data collection using measurements made from a string or similar phantom. A new hypothesis is described, which is that placental resistance is controlled on a timescale of a few seconds in order to maintain the umbilical artery flow rate constant. This hypothesis originates from observations made in a 1989 paper that investigated the relationship between the umbilical artery heart rate and resistance index. The key observation was that changes in heart rate were followed a few seconds later by changes in resistance index. It is proposed that the basis for the control could be endothelial detection of changes in WSS. Modern ultrasound systems have the technical capability to further investigate this hypothesis.</p>","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295217","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}
Nassim Mohamedi, Alexis F Guédon, Louise Z Wang, Rayan Seddiki, Jonas Sitruk, Jean-Baptiste de Fréminville, Lina Khider, Marc Sapoval, Emmanuel Messas, Tristan Mirault, Guillaume Goudot
{"title":"Evaluation of Ultrasound Microflow Imaging as an Assessment Tool for Digital Arteries in Thromboangiitis Obliterans.","authors":"Nassim Mohamedi, Alexis F Guédon, Louise Z Wang, Rayan Seddiki, Jonas Sitruk, Jean-Baptiste de Fréminville, Lina Khider, Marc Sapoval, Emmanuel Messas, Tristan Mirault, Guillaume Goudot","doi":"10.1016/j.ultrasmedbio.2025.05.001","DOIUrl":"https://doi.org/10.1016/j.ultrasmedbio.2025.05.001","url":null,"abstract":"<p><strong>Purpose: </strong>Thromboangiitis obliterans (TAO) diagnosis is challenging, and arterial imaging plays a major role in identifying distal artery occlusions. The ultrasonic micro-flow imaging (MFI) mode aims to identify small vessels better using high frame rates and adapted filters. Our objective was to compare the digital arterial characterization performance of MFI with digital subtraction angiography (DSA).</p><p><strong>Materials and methods: </strong>We conducted a prospective single-center analysis of patients with suspected TAO to compare DSA results to MFI. Ultrasonic scanning was performed on the ten fingers with a longitudinal view using a 4-18 MHz probe. Four-limb angiography was performed following a standardized protocol.</p><p><strong>Results: </strong>Twenty patients with confirmed TAO (median age 48 years) and seven (median age 40 years) with initially suspected TAO refuted after diagnostic work-up were included. The agreement for detecting arterial occlusion between MFI and DSA was good (Kappa coefficient of 0.83 [0.77‒0.90]). Patency of all digital arteries was found in patients who had ruled-out TAO. Qualitative alterations of the digital arteries were also noted in TAO, with non-parallel walls and a smaller, irregular diameter.</p><p><strong>Conclusion: </strong>Ultrasound imaging using MFI mode for digital artery analysis is a promising contender to DSA for diagnosing TAO. Careful analysis allows for the detection of occlusion-recovery, flow analysis, and the detection of parietal arterial anomalies. This non-invasive examination could, therefore, become a major tool for assessing digital arteries in cases of suspected TAO.</p>","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250535","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}
Zhiyu Sheng, Ran Wei, Mengyue Chen, Matthew B Wielgat, Dhanansayan Shanmuganayagam, Edith Tzeng, Xuecang Geng, Xiaoning Jiang, Kang Kim
{"title":"Experimental Evaluation of an Array Transducer for Ultrasound Thermal Strain Imaging: Phantom and In Vivo Studies.","authors":"Zhiyu Sheng, Ran Wei, Mengyue Chen, Matthew B Wielgat, Dhanansayan Shanmuganayagam, Edith Tzeng, Xuecang Geng, Xiaoning Jiang, Kang Kim","doi":"10.1016/j.ultrasmedbio.2025.05.016","DOIUrl":"https://doi.org/10.1016/j.ultrasmedbio.2025.05.016","url":null,"abstract":"<p><strong>Objective: </strong>Characterization of atherosclerosis plaque (AP) is critical for diagnosing rupture-prone AP that directly causes stroke and heart attack, and for guiding in-time interventions and avoiding unnecessary surgeries for stable cases. Ultrasound thermal strain imaging (US-TSI) is known to be capable of characterizing lipids, an important feature of rupture-prone AP. However, before translating US-TSI to in vivo clinical applications, significant technical challenges must be overcome, primarily the requirements of a well-controlled heating strategy to achieve a rapid, safe and spatial-temporal-precise local tissue temperature increase.</p><p><strong>Methods: </strong>To address these issues, we recently developed a novel US-TSI transducer that integrates dual ultrasound heating arrays that use the thermal effect of the acoustic radiation force, and an ultrasound imaging array to reconstruct the spatial thermal strain map.</p><p><strong>Results: </strong>This article presents the first comprehensive test results of our new US-TSI transducer including benchtop US-TSI experiments on ultrasound gelatin phantoms with spatial temperature measurements to compare the thermal strain pattern and the corresponding 2-D temperature map, and US-TSI experiments on a pig with temperature measurements to verify the in vivo feasibility and safety further. A clear thermal strain pattern was obtained as a maximum of -0.25% in phantom and -0.08% in vivo, which corresponds with a reasonable temperature increase, 2.5°C in the phantom and 0.9°C in vivo. There was also a high resemblance between the thermal strain pattern and corresponding temperature measurements.</p><p><strong>Conclusion: </strong>The results demonstrate the effectiveness and safety of performing US-TSI using our new array transducer.</p>","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250536","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}
Brent K Hoffmeister, Grant R Jenson, Amalia M Bay, Ann M Viano, Phyu Sin M Myat, Cecille Labuda, Grace I Nehring, Emily E Bingham, Blake C Lawler, Kate E Hazelwood
{"title":"Fundamental Ultrasonic Properties of Fresh and Formalin Fixed Brain Visualized as Parametric Images.","authors":"Brent K Hoffmeister, Grant R Jenson, Amalia M Bay, Ann M Viano, Phyu Sin M Myat, Cecille Labuda, Grace I Nehring, Emily E Bingham, Blake C Lawler, Kate E Hazelwood","doi":"10.1016/j.ultrasmedbio.2025.04.020","DOIUrl":"https://doi.org/10.1016/j.ultrasmedbio.2025.04.020","url":null,"abstract":"<p><strong>Objective: </strong>The brain is a complex organ with multiple tissue types and a complicated morphology of lobes, folds, ventricles and other structures. The goal of this study was to create detailed parametric images of brain tissue before and after formalin fixation for four ultrasonic parameters: speed of sound (SOS), frequency slope of attenuation (FSA), integrated backscatter coefficient (IBC) and apparent integrated backscatter (AIB).</p><p><strong>Methods: </strong>Twenty-three, 1-cm thick slices of brain tissue were prepared from the sagittal and coronal planes of nine bovine brains. Ultrasonic measurements were performed using an immersion scanning system equipped with a 5 MHz focused transducer moved in 615 μm steps.</p><p><strong>Results: </strong>Measured values, reported as mean ± standard deviation (representing variation between specimen means) averaged over all measurements on all specimens of fresh tissue, were (1535 ± 2) m/s for SOS, (0.546 ± 0.037) dB/cm/MHz for FSA, (0.402 ± 0.165) × 10<sup>-3</sup> cm<sup>-1</sup> str<sup>-1</sup> for IBC and (-60.1 ± 1.1) dB for AIB measured relative to a planar glass reflector. Regions of white matter were characterized by higher values of SOS and FSA, and lower values of AIB and IBC. Formalin fixation caused up to a 0.6% increase in SOS, up to a 2% increase in AIB, up to a 20% increase in FSA and up to a 55% increase in IBC averaged over all measurements on all specimens.</p><p><strong>Conclusion: </strong>Tissue structures and white matter were clearly distinguishable in most parametric images. Formalin fixation produced significant changes in all four ultrasonic parameters.</p>","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227372","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}
Weibo Zeng, Yanni He, Renhao Xu, Wuping Mai, Yufan Chen, Sushu Li, Wenhong Yi, Li Ma, Ran Xiong, Hongmei Liu
{"title":"From Guidelines to Intelligence: How AI Refines Thyroid Nodule Biopsy Decisions.","authors":"Weibo Zeng, Yanni He, Renhao Xu, Wuping Mai, Yufan Chen, Sushu Li, Wenhong Yi, Li Ma, Ran Xiong, Hongmei Liu","doi":"10.1016/j.ultrasmedbio.2025.05.009","DOIUrl":"https://doi.org/10.1016/j.ultrasmedbio.2025.05.009","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the value of combining American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) with the Demetics ultrasound diagnostic system in reducing the rate of fine-needle aspiration (FNA) biopsies for thyroid nodules.</p><p><strong>Methods: </strong>A retrospective study analyzed 548 thyroid nodules from 454 patients, all meeting ACR TI-RADS guidelines (category ≥3 and diameter ≥10 mm) for FNA. Nodule was reclassified using the combined ACR TI-RADS and Demetics system (De TI-RADS), and the biopsy rates were compared.</p><p><strong>Results: </strong>Using ACR TI-RADS alone, the biopsy rate was 70.6% (387/548), with a positive predictive value (PPV) of 52.5% (203/387), an unnecessary biopsy rate of 47.5% (184/387) and a missed diagnosis rate of 11.0% (25/228). Incorporating Demetics reduced the biopsy rate to 48.1% (264/548), the unnecessary biopsy rate to 17.4% (46/265) and the missed diagnosis rate to 4.4% (10/228), while increasing PPV to 82.6% (218/264). All differences between ACR TI-RADS and De TI-RADS were statistically significant (p < 0.05).</p><p><strong>Conclusion: </strong>The integration of ACR TI-RADS with the Demetics system improves nodule risk assessment by enhancing diagnostic and efficiency. This approach reduces unnecessary biopsies and missed diagnoses while increasing PPV, offering a more reliable tool for clinicians and patients.</p>","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200622","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}
Bo-Ji Liu, Yun-Yun Liu, Jing Wan, Ying Zhang, Di Ou, Hong-Feng He, John P Pineda, Hong Han, Yi-Feng Zhang, Hui-Xiong Xu
{"title":"New Thyroid Imaging Reporting and Data System (TIRADS) Based on Ultrasonography Features for Follicular Thyroid Neoplasms: A Multicenter Study.","authors":"Bo-Ji Liu, Yun-Yun Liu, Jing Wan, Ying Zhang, Di Ou, Hong-Feng He, John P Pineda, Hong Han, Yi-Feng Zhang, Hui-Xiong Xu","doi":"10.1016/j.ultrasmedbio.2025.05.004","DOIUrl":"https://doi.org/10.1016/j.ultrasmedbio.2025.05.004","url":null,"abstract":"<p><strong>Objective: </strong>Preoperative diagnosis of follicular thyroid neoplasm (FTN) (including follicular thyroid adenoma [FTA] and follicular thyroid carcinoma [FTC]) is difficult and the current ultrasound risk stratification systems (RSSs) for thyroid nodules are not suitable for FTN. Therefore, this study aimed to establish a new RSS for FTN as a useful preoperative evaluation to reduce missed diagnoses and unnecessary biopsies.</p><p><strong>Methods: </strong>We included 535 FTNs from four hospitals in this retrospective study. All nodules were divided randomly into a test group (n = 370; 111 FTCs and 259 FTAs) and a validation group (n = 165; 51 FTCs and 114 FTAs). The ultrasound features of each nodule were analyzed. Thyroid Imaging Reporting and Data System (TIRADS) of FTN (FTN-TIRADS) was established based on the results of univariate analysis and logistic regression of ultrasound features. Each nodule was evaluated and classified by these four RSSs (RSS from European Thyroid Association [EU-RSS], RSS from the American Thyroid Association [ATA-RSS], TIRADS from the American College of Radiology [ACR-TIRADS], TIRADS from China [C-TIRADS]) and FTN-TIRADS, respectively. Receiver operating characteristic curve analysis was performed and the area under the receiver operator characteristic curve (AUC) was used to evaluate the diagnostic value of the RSSs mentioned above. The diagnostic value of FTN-TIRADS in the validation group was verified and compared with the test group and other four RSSs. The unnecessary rates of fine needle aspiration (FNA) were calculated and compared between FTN-RIRADS and the other four RSSs.</p><p><strong>Results: </strong>The test group and validation group included 370 patients (86 male patients) and 165 patients (48 male patients). The following ultrasound features were independent risk factors and included in FTN-TIRADS: nodule composition, echogenicity, calcifications, halo sign, indistinct boundary with the thyroid capsule. Nodules were classified as TR2, TR3, TR4a, TR4b, TR4c, and TR5 with none to five suspicious features described, respectively. The AUC of FTN-TIRADS was 0.855, statistically higher than EU-RSS, ATA-RSS, ACR-TIRADS and C-TIRADS (0.759, 0.759, 0.753, and 0.677, respectively) (all p < 0.05). The FTN-TIRADS of the validation group had similar diagnostic performance to that of the test group (AUC 0.879 vs. AUC 0.855; p = 0.569). The unnecessary FNA rate of the FTN-TIRADS was 41.4%, which was significantly lower than that of EU-RSS (67.3%), ATA-RSS (69.0%), ACR-TIRADS (60.1%), and C-TIRADS (63.2%).</p><p><strong>Conclusions: </strong>FTN-TIRADS achieved better differential diagnosis of FTN than current RSSs and significantly reduced the rate of unnecessary FNA. It can serve as a reliable preoperative noninvasive assessment tool for thyroid follicular tumors, reducing unnecessary FNA and unnecessary surgeries.</p>","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200623","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}
Ming Liang, Shiji Wu, Bing Ou, Jiayi Wu, Haolin Qiu, Xinbao Zhao, Baoming Luo
{"title":"Discriminating Clear Cell From Non-Clear Cell Renal Cell Carcinoma: A Machine Learning Approach Using Contrast-enhanced Ultrasound Radiomics.","authors":"Ming Liang, Shiji Wu, Bing Ou, Jiayi Wu, Haolin Qiu, Xinbao Zhao, Baoming Luo","doi":"10.1016/j.ultrasmedbio.2025.05.006","DOIUrl":"https://doi.org/10.1016/j.ultrasmedbio.2025.05.006","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this investigation is to assess the clinical usefulness of a machine learning model using contrast-enhanced ultrasound (CEUS) radiomics in discriminating clear cell renal cell carcinoma (ccRCC) from non-ccRCC.</p><p><strong>Methods: </strong>A total of 292 patients with pathologically confirmed RCC subtypes underwent CEUS (development set. n = 231; validation set, n = 61) in a retrospective study. Radiomics features were derived from CEUS images acquired during the cortical and parenchymal phases. Radiomics models were developed using logistic regression (LR), support vector machine, decision tree, naive Bayes, gradient boosting machine, and random forest. The suitable model was identified based on the area under the receiver operating characteristic curve (AUC). Appropriate clinical CEUS features were identified through univariate and multivariate LR analyses to develop a clinical model. By integrating radiomics and clinical CEUS features, a combined model was established. A comprehensive evaluation of the models' performance was conducted.</p><p><strong>Results: </strong>After the reduction and selection process were applied to 2250 radiomics features, the final set of 8 features was considered valuable. Among the models, the LR model had the highest performance on the validation set and showed good robustness. In both the development and validation sets, both the radiomics (AUC, 0.946 and 0.927) and the combined models (AUC, 0.949 and 0.925) outperformed the clinical model (AUC, 0.851 and 0.768), showing higher AUC values (all p < 0.05). The combined model exhibited favorable calibration and clinical benefit.</p><p><strong>Conclusion: </strong>The combined model integrating clinical CEUS and CEUS radiomics features demonstrated good diagnostic performance in discriminating ccRCC from non-ccRCC.</p>","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227371","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":"Predicting Benign and Malignant Subpleural Pulmonary Lesions With Nomogram Model Using Clinical and B-mode Ultrasound Parameters.","authors":"Pablo Echevarría Díez-Canedo, Yale Tung-Chen","doi":"10.1016/j.ultrasmedbio.2025.05.003","DOIUrl":"https://doi.org/10.1016/j.ultrasmedbio.2025.05.003","url":null,"abstract":"","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144250537","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}
Alina R Kline-Schoder, Fotios N Tsitsos, Alec J Batts, Melody R DiBenedetto, Keyu Liu, Sua Bae, Elisa E Konofagou
{"title":"Response of Serum-Isolated Extracellular Vesicles to Focused Ultrasound-Mediated Blood-Brain Barrier Opening.","authors":"Alina R Kline-Schoder, Fotios N Tsitsos, Alec J Batts, Melody R DiBenedetto, Keyu Liu, Sua Bae, Elisa E Konofagou","doi":"10.1016/j.ultrasmedbio.2025.04.019","DOIUrl":"10.1016/j.ultrasmedbio.2025.04.019","url":null,"abstract":"<p><strong>Objective: </strong>To characterize the response of extracellular vesicles (EV) in the serum of mice and Alzheimer's disease (AD) patients following focused ultrasound (FUS)-mediated blood-brain barrier (BBB) opening (FUS-BBBO) as a means to improve liquid biopsy.</p><p><strong>Methods: </strong>Blood was collected from C57BL/6 mice before, and one hour after FUS-BBBO, and from AD patients before, one hour after, and three days after FUS-BBBO. EVs were isolated from serum using the Exoquick precipitation solution and their concentration was quantified using nanoparticle tracking analysis. The transcriptomic and proteomic content of EVs from mice was assessed using RNA sequencing and mass spectrometry protein analysis respectively. Additionally, the release of EVs in mice was inhibited using the GW4869 drug to assess the role of EVs in the restoration of the BBB. Finally, the biomarker content of EVs in AD patients was detected using a Luminex multiplex assay.</p><p><strong>Results: </strong>We observed a 164±85% (95% confidence interval: 78.998 - 249.202) increase in murine EV concentration one hour after treatment, as well as an increase in EV RNA associated with FUS-BBBO neuroimmunotherapy. Inhibition of EVs reduced the inflammatory response and BBBO volume in mice. Patient EV concentration also increased one hour after treatment and was dependent on the volume of BBB opening three days post-treatment. Furthermore, EV isolation was found to significantly enhance (p<0.05) the detection of FUS-BBBO-induced amplification of AD and CNS biomarkers such as GFAP, beta-amyloid 42 and phosphorylated tau 181, exhibiting on average a 1.2 times higher log-fold change in biomarker levels in isolated EVs compared to total serum.</p><p><strong>Conclusion: </strong>Overall, we hereby present the first evidence of altered murine and AD patient EV concentration and content in response to FUS-BBBO, providing evidence of EVs' role within FUS-BBBO neuroimmunotherapy as well as their utility in improving FUS-BBBO biomarker amplification. Our results pave the way for clinical applications of EV-based liquid biopsy in patients with neurodegenerative diseases following FUS-BBBO, as a way of noninvasively monitoring disease progression.</p>","PeriodicalId":49399,"journal":{"name":"Ultrasound in Medicine and Biology","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144227373","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}