Yi Huang, Feifei Zhao, Yanjun Xie, F William Mauldin, Alexander L Klibanov, John A Hossack
{"title":"High-Resolution Ultrasound Molecular Imaging With Incremental Burst Sequence: In Vitro and In Vivo Validation.","authors":"Yi Huang, Feifei Zhao, Yanjun Xie, F William Mauldin, Alexander L Klibanov, John A Hossack","doi":"10.1109/TUFFC.2025.3576337","DOIUrl":"10.1109/TUFFC.2025.3576337","url":null,"abstract":"<p><p>Ultrasound localization microscopy (ULM) enables super-resolution ultrasound (SRUS) imaging of microvasculature, while ultrasound molecular imaging (USMI) characterizes molecular signatures using microbubbles (MBs) targeted to specific biomarkers. Although the colocalization of SRUS and USMI has been demonstrated previously, USMI resolution is limited by ultrasound diffraction-based effects and does not match the super-resolved microvasculature. This study introduces the incremental burst sequence (IBS) method to induce the population of polydisperse targeted MBs to burst progressively, achieving MB spatial separation and enabling high-resolution USMI (HR-USMI) localization. The IBS method employs interleaved imaging and bursting pulses, with transmit voltages of bursting pulses incrementally increased to produce a gradual rise in the acoustic pressure. IBS is first validated optically in vitro using a cellulose tubing phantom, and MB remaining count during IBS is measured. Thereafter, in vivo validation is performed in a murine tumor model, and the intratumoral targeted MB signal intensity is measured during IBS. Furthermore, high-frame-rate data for SRUS and IBS data for HR-USMI are acquired from a single bolus injection of MBs to generate composite images with high-resolution molecular signatures superimposed on the tumor microvasculature. Both in vitro and in vivo results validate the technical feasibility of the proposed IBS method. In addition, we demonstrate that higher bursting pulse repetitions lead to a faster disruption of the MB population during IBS. Finally, HR-USMI signals localized within a $50times 50~mu $ m grid are aligned with microvessels resolved better than $100~mu $ m, presenting a combination of molecular signatures and anatomical structures at fine resolution.</p>","PeriodicalId":13322,"journal":{"name":"IEEE transactions on ultrasonics, ferroelectrics, and frequency control","volume":"PP ","pages":"445-459"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144225357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Byung Min Park, Eleonora Munoz-Ibarra, Hugues Favre, Liam Silvera, Baptiste Heiles, David Maresca
{"title":"A Low-Cost Photobioreactor for Scalable Gas Vesicle Production.","authors":"Byung Min Park, Eleonora Munoz-Ibarra, Hugues Favre, Liam Silvera, Baptiste Heiles, David Maresca","doi":"10.1109/TUFFC.2025.3623375","DOIUrl":"10.1109/TUFFC.2025.3623375","url":null,"abstract":"<p><p>Gas vesicles (GVs) are air-filled protein nanostructures (~85 nm diameter and ~500 nm length) with the physical property to scatter sound. This new class of contrast agent serves as an acoustic analog to green fluorescent proteins and enables ultrasound imaging of cells that have been genetically labeled with GVs. To date, methods to produce GVs rely on expensive CO2 shakers, limiting accessibility and scalability. In this study, we present a cost-effective and scalable protocol to produce GVs using an adapted bubble column photobioreactor design. This production method operates at approximately 10% of the cost of the state-of-theart while utilizing off-the-shelf components for broader accessibility and dissemination. We characterized GVs produced with both photobioreactor and shaker-incubator production methods using hydrostatic collapse pressure (CP) measurements, hydrodynamic diameter measurements, and ultrasound imaging. Our results demonstrate that GVs produced with both methods exhibit identical physicochemical properties, ensuring intercompatibility. In summary, this new protocol to produce GVs lowers the barrier to producing GVs in research labs, thereby creating the possibility of a broader use of GVs as ultrasound contrast agents and biosensors for a wide array of biomedical applications.</p>","PeriodicalId":13322,"journal":{"name":"IEEE transactions on ultrasonics, ferroelectrics, and frequency control","volume":"PP ","pages":"392-401"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cross Amplitude Modulation Imaging: Theory and Basic Principles.","authors":"Hugues Favre, David Maresca","doi":"10.1109/TUFFC.2025.3614145","DOIUrl":"10.1109/TUFFC.2025.3614145","url":null,"abstract":"<p><p>The introduction of genetically encoded gas vesicles (GVs), protein nanostructures with the ability to scatter sound, has created the possibility for deep tissue cellular imaging. GVs establish a platform for biomolecular engineering and were successfully repurposed into acoustic reporter genes and acoustic biosensors. Alongside molecular engineering developments, a method called cross amplitude modulation (xAM) has emerged as the gold standard for nondestructive ultrasound imaging of GVs, thanks to its sensitivity and specificity in living biological tissues. Here, we present latest xAM theory and imaging principles. Specifically, we report 1) analytical expressions for the X-wave beamwidth and primary-tosecondary lobes distance; 2) experimental observations of nondiffractive xAM beams; 3) a method to modulate the secondary lobe level of xAM beams; 4) a demonstration of the incoherent nature of the xAM image noise that can be leverage to increase sensitivity through frame averaging; and 5) a beamforming formalism to enhance xAM contrast-to-noise ratio without reducing framerate. Ultimately, the rise of the field of biomolecular ultrasound will rest on the co-development of genetically encoded probes and dedicated imaging methods such as xAM and its 3-D extension, nonlinear sound-sheet microscopy (NSSM).</p>","PeriodicalId":13322,"journal":{"name":"IEEE transactions on ultrasonics, ferroelectrics, and frequency control","volume":"PP ","pages":"460-469"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lok Yin Nicholas Chan, Sarina Grewal, Shusei Kawara, Jiho Kim, James J Choi, Sophie V Morse
{"title":"Film-Based Cell Culture Device and In Vitro Setup for Ultrasound Modulation.","authors":"Lok Yin Nicholas Chan, Sarina Grewal, Shusei Kawara, Jiho Kim, James J Choi, Sophie V Morse","doi":"10.1109/TUFFC.2025.3569498","DOIUrl":"10.1109/TUFFC.2025.3569498","url":null,"abstract":"<p><p>Conventional ultrasound in vitro systems, such as petri dishes and well plates often introduce acoustic reflections and pressure accumulation, compromising the reliability and reproducibility of experimental results. Custom sonication vessels and setups, while addressing some of these issues, often involve complicated assembly processes and can be compatible only with specific experimental setups. To address these limitations, we developed an easy-to-use 3-D-printed device that utilizes parafilm on the top and bottom, enabling the device chamber to be optimized for quick assembly, contamination prevention, and ultrasound wave propagation. Pressure field mapping with a needle-hydrophone confirmed a predictable ultrasound pressure distribution within the device. In addition to parafilm, Mylar and polystyrene films were tested showing minimal interference when measuring the pressure field. Rat-derived primary astrocytes and microglial cells, as well as immortalized human embryonic kidney-derived HEK293t cells, were cultured directly onto precoated Mylar films, which exhibit superior optical and acoustic transparency. These cell types were selected due to their wide range of potential applications, especially in the emerging field of ultrasound modulation and sonogenetics. Cell viability was assessed using trypan blue exclusion and the results demonstrate the feasibility of seeding cells onto Mylar film. The device maintained sterility with no leakage, confirming its efficacy and reliability for cell culture experiments. This novel 3-D-printed device provides more control over the ultrasound parameters delivered to cells. Its adaptable design supports flexible modifications, allowing researchers to tailor it to specific experimental needs, thereby improving the accuracy and reproducibility of in vitro ultrasound modulation studies.</p>","PeriodicalId":13322,"journal":{"name":"IEEE transactions on ultrasonics, ferroelectrics, and frequency control","volume":"PP ","pages":"426-435"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Filip Ivanovski, Vid Jazbec, Nina Varda, Roman Jerala, Mojca Bencina
{"title":"Ultrasound-Responsive Mammalian Cell Synthetic Biology.","authors":"Filip Ivanovski, Vid Jazbec, Nina Varda, Roman Jerala, Mojca Bencina","doi":"10.1109/TUFFC.2025.3570813","DOIUrl":"10.1109/TUFFC.2025.3570813","url":null,"abstract":"<p><p>Sonogenetics is developing into a powerful tool in synthetic biology. The coupling of ultrasound (US) with genetically engineered effectors enables noninvasive and precise control of cellular and molecular processes. Building on established techniques such as optogenetics, it overcomes the limits of tissue penetration and invasiveness, making it a promising tool for both research and therapeutic applications. Recent advances in acoustic contrast agents, such as microbubbles and gas vesicles (GVs), have improved the mechanical effects of US on cells, extending its application to various biological systems. This review highlights recent advances and challenges, such as standardization of parameters and understanding of underlying mechanisms, and outlines future directions for US-guided cellular control.</p>","PeriodicalId":13322,"journal":{"name":"IEEE transactions on ultrasonics, ferroelectrics, and frequency control","volume":"PP ","pages":"416-425"},"PeriodicalIF":4.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control Publication Information","authors":"","doi":"10.1109/TUFFC.2025.3640482","DOIUrl":"https://doi.org/10.1109/TUFFC.2025.3640482","url":null,"abstract":"","PeriodicalId":13322,"journal":{"name":"IEEE transactions on ultrasonics, ferroelectrics, and frequency control","volume":"72 12","pages":"C2-C2"},"PeriodicalIF":3.7,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=11300335","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145754229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control Publication Information","authors":"","doi":"10.1109/TUFFC.2025.3633227","DOIUrl":"https://doi.org/10.1109/TUFFC.2025.3633227","url":null,"abstract":"","PeriodicalId":13322,"journal":{"name":"IEEE transactions on ultrasonics, ferroelectrics, and frequency control","volume":"72 11","pages":"C2-C2"},"PeriodicalIF":3.7,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=11266974","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145584654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Theoretical Foundations of the Echo Envelope Statistical Modeling: A Tutorial","authors":"François Destrempes;Guy Cloutier","doi":"10.1109/TUFFC.2025.3632084","DOIUrl":"10.1109/TUFFC.2025.3632084","url":null,"abstract":"The purpose of this methods and concepts tutorial is to present the homodyned K-distribution (HKD) statistical modeling of the echo envelope of received radio frequency (RF) signals in the context of medical quantitative ultrasound (QUS) imaging, with the aim of explaining its physical, mathematical, and statistical foundations. Several notions and equations are recalled from previous works on HKD modeling and estimation methods. Proofs of claims are presented in Appendices that can be found in Supplementary Materials. Some descriptions have been completed or refined without modifying the main conclusions on HKD or mixtures of HKDs. Mixtures of HKDs are recalled, as well as other models proposed in previous works, such as the generalized KD (GKD), HKD with additive Gaussian noise (HKDN), and the generalized HKD (GHKD), the latter resorting to the generalized central limit theorem (CLT) in the case where the scattering cross section has infinite variance. This article also presents three innovations on the topic: 1) a revised derivation of the HKD model based on Stein’s condition to obtain an explicit rate of convergence of the CLT in the case of weakly dependent terms, corresponding to ultrasound (US) scatterers; 2) HKD imaging under frequency-domain filtering of RF signals, yielding information on second-order statistics of the echo envelope; and 3) quantitative results on the Kolmogorov distance between the HKD and other distributions (Nakagami and Rice distributions, GKD, HKDN, and GHKD) together with the domains insuring validity (i.e., statistical equivalence with a confidence level of 0.05).","PeriodicalId":13322,"journal":{"name":"IEEE transactions on ultrasonics, ferroelectrics, and frequency control","volume":"72 12","pages":"1566-1581"},"PeriodicalIF":3.7,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145512607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Taran Anusorn;Omar Barrera;Jack Kramer;Ian Anderson;Ziqian Yao;Vakhtang Chulukhadze;Ruochen Lu
{"title":"Practical Demonstrations of FR3-Band Thin-Film Lithium Niobate Acoustic Filter Design","authors":"Taran Anusorn;Omar Barrera;Jack Kramer;Ian Anderson;Ziqian Yao;Vakhtang Chulukhadze;Ruochen Lu","doi":"10.1109/TUFFC.2025.3632215","DOIUrl":"10.1109/TUFFC.2025.3632215","url":null,"abstract":"This article presents an approach to control the operating frequency and fractional bandwidth (FBW) of miniature acoustic filters in thin-film lithium niobate (TFLN). More specifically, we used firstorder antisymmetric (A1) mode lateral-field-excited bulk acoustic wave resonators (XBARs) to achieve efficient operation at 20.5 GHz. Our technique leverages the thickness-dependent resonant frequency of A1 XBARs, combined with the in-plane anisotropic properties of 128. Y-cut TFLN, to customize filter characteristics. The implemented three-element ladder filter prototype achieves an insertion loss (IL) of only 1.79 dB and a controlled 3-dB FBW of 8.58% at 20.5 GHz, with an out-of-band (OoB) rejection greater than 14.9 dB across the entire frequency range 3 (FR3) band, while featuring a compact footprint of 0.90 × 0.74 mm2. Moreover, an eight-element filter prototype shows an IL of 3.80 dB, an FBW of 6.12% at 22.0 GHz, and a high OoB rejection of 22.97 dB, demonstrating the potential for expanding to higher order filters. As frequency allocation requirements become more stringent in future FR3 bands, our technique showcases promising capability in enabling compact and monolithic filter banks toward next-generation acoustic filters for 6G and beyond.","PeriodicalId":13322,"journal":{"name":"IEEE transactions on ultrasonics, ferroelectrics, and frequency control","volume":"72 12","pages":"1650-1662"},"PeriodicalIF":3.7,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145503631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yifei Li;Hui Zhu;Yi Zeng;Shixiao W. Jiang;Xiran Cai
{"title":"Real-Time Heterogeneous Helical Wave Spectrum Method for Transabdominal Passive Acoustic Mapping","authors":"Yifei Li;Hui Zhu;Yi Zeng;Shixiao W. Jiang;Xiran Cai","doi":"10.1109/TUFFC.2025.3631731","DOIUrl":"10.1109/TUFFC.2025.3631731","url":null,"abstract":"In focused ultrasound (FUS) therapy, passive acoustic mapping (PAM) with convex arrays is often employed to monitor the cavitation activity in the human abdomen, given their large acoustic window. However, phase aberration caused by the speed-of-sound (SoS) heterogeneity in the abdominal wall degrades the image quality, leading to inaccurate localization of the cavitation source and, hence, deteriorates the safety and efficacy level of the therapy. In this work, we derive the general solution to the wave equation in SoS heterogeneous media in polar coordinates. With the solution, we propose the real-time heterogeneous helical wave spectrum (HHWS) method to account for SoS heterogeneity in transabdominal PAM with convex arrays. In both the in silico and in vitro experiments mimicking transabdominal PAM imaging of single and multiple microbubble (MB) cavitation source(s) in humans, the results clearly demonstrated the phase aberration-correction capability of the HHWS method with improved image quality and source localization accuracy, compared with the helical wave spectrum (HWS) method for homogeneous media. A parallel implementation of the HHWS method realized a several tens of milliseconds image reconstruction speed for phase-aberration-corrected PAM in a large field of view (FOV). Combined with B-mode imaging, real-time dual-mode monitoring of MB cavitation activity in the heterogeneous medium mimicking the human abdominal wall with a single probe has been realized. These results well demonstrated the potential of the HHWS method for transabdominal PAM with convex arrays, for safe, effective, and controlled cavitation-based FUS therapies.","PeriodicalId":13322,"journal":{"name":"IEEE transactions on ultrasonics, ferroelectrics, and frequency control","volume":"72 12","pages":"1595-1606"},"PeriodicalIF":3.7,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145495463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}