@article{wu_kim_zhang_owens_stocker_chen_kreager_cornett_bautista_kaovasia_et al._2024, title={Rotational Intravascular Multidirectional Ultrasound Catheter for Sonothrombolysis of Retracted Clots: An in Vitro and in Vivo Study}, url={https://doi.org/10.1016/j.eng.2024.03.021}, DOI={10.1016/j.eng.2024.03.021}, abstractNote={Thromboembolism in blood vessels poses a serious risk of stroke, heart attack, and even sudden death if not properly managed. Sonothrombolysis combined with ultrasound contrast agents has emerged as a promising approach for the effective treatment of thromboembolism. Recent reports have highlighted the potential of intravascular sonothrombolysis as a safe and effective treatment modality for deep vein thrombosis (DVT). However, its efficiency has not been validated through in vivo testing of retracted clots. This study aimed to develop a miniaturized multidirectional transducer featuring two 4-layer lead zirconate titanate (PZT-5A) stacks with an aperture size of 1.4 mm × 1.4 mm, enabling both forward- and side-looking treatment. Integrated into a custom two-lumen 10-French (Fr) catheter, the capability of this device for intravascular sonothrombolysis was validated both in vitro and in vivo. With low-dose tissue plasminogen activators and nanodroplets, the rotational multidirectional transducer reduced the retracted clot mass (800 mg) by an average of 52% within 30 min during in vitro testing. The lysis rate was significantly higher by 37% than that in a forward-viewing transducer without rotation. This improvement was particularly noteworthy in the treatment of retracted clots. Notably, a long-retracted clot (> 10 cm) was successfully treated within 40 min in vivo by creating a flow channel with a diameter > 4 mm in a porcine DVT model. In conclusion, these findings strongly suggest the potential of this technique for clinical applications in sonothrombolysis, offering a feasible solution for effectively treating thromboembolism, particularly in challenging cases involving retracted clots.}, journal={Engineering}, author={Wu, Huaiyu and Kim, Jinwook and Zhang, Bohua and Owens, Gabe and Stocker, Greyson and Chen, Mengyue and Kreager, Benjamin C. and Cornett, Ashley and Bautista, Kathlyne and Kaovasia, Tarana and et al.}, year={2024}, month={Jun} }
 @inproceedings{wang_wu_zhang_chen_shovon_ware_jiang_2023, title={A Miniaturized Transducer for Sonothrombolysis with Vortex Phase Modulation}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85178588849&partnerID=MN8TOARS}, DOI={10.1109/IUS51837.2023.10307202}, abstractNote={Vortex ultrasound based on phase modulation techniques has become one of the most fascinating frontiers of therapy including sonothrombolysis. But the most frequently used acoustic vortex generating method, multi-elements transducer array with independent and distinct components, can only be utilized in a limited quantity, have expensive constructions and circuitry, and require rigorous calibration and tuning, which restricts their potential uses. Based on Spiral Phase Plate (SPP) principle and Digital Light Processing (DLP) bottom-up printing method, we propose a miniaturized transducer combined with an SPP lens to generate vortex ultrasound for the sake of low complexity, cheap fabrication, and tunable flexibility. In this work, a 5.1 MHz transducer of a 2 mm × 2 mm aperture was developed generating an acoustic vortex with a distinguished angular phase change gradient and acceptable acoustic pressure maximum of 0.7 MPa in 4.4 mm distance away at 100V <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">pp</inf> input.}, booktitle={IEEE International Ultrasonics Symposium, IUS}, author={Wang, J. and Wu, H. and Zhang, B. and Chen, M. and Shovon, S. and Ware, H. and Jiang, X.}, year={2023} }
 @article{zhang_wu_kim_welch_cornett_stocker_nogueira_kim_owens_dayton_et al._2023, title={A Model of High-Speed Endovascular Sonothrombolysis with Vortex Ultrasound-Induced Shear Stress to Treat Cerebral Venous Sinus Thrombosis}, volume={6}, ISSN={["2639-5274"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85152207991&partnerID=MN8TOARS}, DOI={10.34133/research.0048}, abstractNote={This research aims to demonstrate a novel vortex ultrasound enabled endovascular thrombolysis method designed for treating cerebral venous sinus thrombosis (CVST). This is a topic of substantial importance since current treatment modalities for CVST still fail in as many as 20% to 40% of the cases, and the incidence of CVST has increased since the outbreak of the coronavirus disease 2019 pandemic. Compared with conventional anticoagulant or thrombolytic drugs, sonothrombolysis has the potential to remarkably shorten the required treatment time owing to the direct clot targeting with acoustic waves. However, previously reported strategies for sonothrombolysis have not demonstrated clinically meaningful outcomes (e.g., recanalization within 30 min) in treating large, completely occluded veins or arteries. Here, we demonstrated a new vortex ultrasound technique for endovascular sonothrombolysis utilizing wave-matter interaction-induced shear stress to enhance the lytic rate substantially. Our in vitro experiment showed that the lytic rate was increased by at least 64.3% compared with the nonvortex endovascular ultrasound treatment. A 3.1-g, 7.5-cm-long, completely occluded in vitro 3-dimensional model of acute CVST was fully recanalized within 8 min with a record-high lytic rate of 237.5 mg/min for acute bovine clot in vitro. Furthermore, we confirmed that the vortex ultrasound causes no vessel wall damage over ex vivo canine veins. This vortex ultrasound thrombolysis technique potentially presents a new life-saving tool for severe CVST cases that cannot be efficaciously treated using existing therapies.}, journal={RESEARCH}, author={Zhang, Bohua and Wu, Huaiyu and Kim, Howuk and Welch, Phoebe J. and Cornett, Ashley and Stocker, Greyson and Nogueira, Raul G. and Kim, Jinwook and Owens, Gabe and Dayton, Paul A. and et al.}, year={2023}, month={Jan}, pages={1–13} }
 @article{xue_zhang_moon_xu_huang_sharma_jiang_2023, title={Development of a Wearable Ultrasound Transducer for Sensing Muscle Activities in Assistive Robotics Applications}, volume={13}, ISSN={["2079-6374"]}, url={https://doi.org/10.3390/bios13010134}, DOI={10.3390/bios13010134}, abstractNote={Robotic prostheses and powered exoskeletons are novel assistive robotic devices for modern medicine. Muscle activity sensing plays an important role in controlling assistive robotics devices. Most devices measure the surface electromyography (sEMG) signal for myoelectric control. However, sEMG is an integrated signal from muscle activities. It is difficult to sense muscle movements in specific small regions, particularly at different depths. Alternatively, traditional ultrasound imaging has recently been proposed to monitor muscle activity due to its ability to directly visualize superficial and at-depth muscles. Despite their advantages, traditional ultrasound probes lack wearability. In this paper, a wearable ultrasound (US) transducer, based on lead zirconate titanate (PZT) and a polyimide substrate, was developed for a muscle activity sensing demonstration. The fabricated PZT-5A elements were arranged into a 4 × 4 array and then packaged in polydimethylsiloxane (PDMS). In vitro porcine tissue experiments were carried out by generating the muscle activities artificially, and the muscle movements were detected by the proposed wearable US transducer via muscle movement imaging. Experimental results showed that all 16 elements had very similar acoustic behaviors: the averaged central frequency, −6 dB bandwidth, and electrical impedance in water were 10.59 MHz, 37.69%, and 78.41 Ω, respectively. The in vitro study successfully demonstrated the capability of monitoring local muscle activity using the prototyped wearable transducer. The findings indicate that ultrasonic sensing may be an alternative to standardize myoelectric control for assistive robotics applications.}, number={1}, journal={BIOSENSORS-BASEL}, author={Xue, Xiangming and Zhang, Bohua and Moon, Sunho and Xu, Guo-Xuan and Huang, Chih-Chung and Sharma, Nitin and Jiang, Xiaoning}, year={2023}, month={Jan} }
 @article{wu_kreager_chen_zhang_abenojar_exner_jiang_2023, title={Intravascular sonothrombolysis with nanobubbles : <i>in</i>-<i>vitro</i> study}, volume={2023-July}, ISSN={["1944-9380"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85173598275&partnerID=MN8TOARS}, DOI={10.1109/NANO58406.2023.10231295}, abstractNote={Thrombosis-related morbidity and mortality pose a significant global health challenge. Existing approaches for thrombolysis, such as administering fibrinolytic agents or performing mechanical thrombectomy, come with prolonged treatment duration and risks of complications. Recent research proposes a more effective and safer alternative with contrast agents mediated ultrasound thrombolysis. Nonetheless, effectively treating retracted clots remains problematic due to their dense structure. To tackle this issue, we introduce an innovative method utilizing a stacked transducer for intravascular sonothrombolysis for higher lysis efficiency, employing a mixture of nanobubbles (NB) and microbubbles (MB). The inclusion of nanobubbles serves to enhance cavitation and improve the breakdown of clot structures. In our study, we employed a 470 kHz transducer with an aperture size of $1.4\times 1.4$ mm2 integrated in a 9-Fr catheter. Preliminary results indicate that NB- and MB/NB-mediated sonothrombolysis led to a 31% and 65% higher lysis rate, respectively, compared to MB-mediated sonothrombolysis in the case of retracted clots. These findings demonstrate the significant potential of nanobubbles in the field of sonothrombolysis applications.}, journal={2023 IEEE 23RD INTERNATIONAL CONFERENCE ON NANOTECHNOLOGY, NANO}, author={Wu, Huaiyu and Kreager, Ben and Chen, Mengyue and Zhang, Bohua and Abenojar, Eric and Exner, Agata A. and Jiang, Xiaoning}, year={2023}, pages={376–379} }
 @misc{zhang_jiang_2023, title={Magnetic Nanoparticles Mediated Thrombolysis-A Review}, volume={4}, ISSN={["2644-1292"]}, url={https://doi.org/10.1109/OJNANO.2023.3273921}, DOI={10.1109/OJNANO.2023.3273921}, abstractNote={Nanoparticles containing thrombolytic medicines have been developed for thrombolysis applications in response to the increasing demand for effective, targeted treatment of thrombosis disease. In recent years, there has been a great deal of interest in nanoparticles that can be navigated and driven by a magnetic field. However, there are few review publications concerning the application of magnetic nanoparticles in thrombolysis. In this study, we examine the current state of magnetic nanoparticles in the application of in vitro and in vivo thrombolysis under a static or dynamic magnetic field, as well as the combination of magnetic nanoparticles with an acoustic field for dual-mode thrombolysis. We also discuss four primary processes of magnetic nanoparticles mediated thrombolysis, including magnetic nanoparticle targeting, magnetic nanoparticle trapping, magnetic drug release, and magnetic rupture of blood clot fibrin networks. This review will offer unique insights for the future study and clinical development of magnetic nanoparticles mediated thrombolysis approaches.}, journal={IEEE OPEN JOURNAL OF NANOTECHNOLOGY}, author={Zhang, Bohua and Jiang, Xiaoning}, year={2023}, pages={109–132} }
 @article{wu_tang_zhang_klippel_jing_yao_jiang_2023, title={Miniaturized Stacked Transducer for Intravascular Sonothrombolysis With Internal-Illumination Photoacoustic Imaging Guidance and Clot Characterization}, volume={70}, ISSN={["1558-2531"]}, url={https://doi.org/10.1109/TBME.2023.3240725}, DOI={10.1109/TBME.2023.3240725}, abstractNote={Thromboembolism in blood vessels can lead to stroke or heart attack and even sudden death unless brought under control. Sonothrombolysis enhanced by ultrasound contrast agents has shown promising outcome on effective treatment of thromboembolism. Intravascular sonothrombolysis was also reported recently with a potential for effective and safe treatment of deep thrombosis. Despite the promising treatment results, the treatment efficiency for clinical application may not be optimized due to the lack of imaging guidance and clot characterization during the thrombolysis procedure. In this paper, a miniaturized transducer was designed to have an 8-layer PZT-5A stacked with an aperture size of 1.4 × 1.4 mm2 and assembled in a customized two-lumen 10-Fr catheter for intravascular sonothrombolysis. The treatment process was monitored with internal-illumination photoacoustic tomography (II-PAT), a hybrid imaging modality that combines the rich contrast of optical absorption and the deep penetration of ultrasound detection. With intravascular light delivery using a thin optical fiber integrated with the intravascular catheter, II-PAT overcomes the penetration depth limited by strong optical attenuation of tissue. In-vitro PAT-guided sonothrombolysis experiments were carried out with synthetic blood clots embedded in tissue phantom. Clot position, shape, stiffness, and oxygenation level can be estimated by II-PAT at clinically relevant depth of ten centimeters. Our findings have demonstrated the feasibility of the proposed PAT-guided intravascular sonothrombolysis with real-time feedback during the treatment process.}, number={8}, journal={IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING}, author={Wu, Huaiyu and Tang, Yuqi and Zhang, Bohua and Klippel, Paul and Jing, Yun and Yao, Junjie and Jiang, Xiaoning}, year={2023}, month={Aug}, pages={2279–2288} }
 @article{sheng_wei_chen_zhang_kim_geng_jiang_kim_2023, title={Quantitative characterization of the ultrasound thermal strains in tissue mimicking phantoms with different oil concentrations}, volume={153}, ISSN={["1520-8524"]}, DOI={10.1121/10.0019122}, abstractNote={Ultrasound thermal strain imaging (US-TSI) has been known for the capability of tissue characterization according to distinct sound speed change in different tissues when temperature increases. US-TSI for detecting lipids in atherosclerosis plaques and fatty livers has previously been reported while some practical challenges were not fully addressed, especially due to physiological motions. To overcome such limitation, we recently developed an ultrasound transducer that combines an acoustic heating array and an imaging array to achieve US-TSI with heating performed in a region of approximately 10 mm by 5 mm by 2 mm within a very short time period of about 50 ms compared both cardiac and breathing motions. To characterize the new US-TSI probe, a thorough benchtop investigation was performed on the relationship among the threekey variables for TSI: thermal strain, temperature increase, and lipid concentration. In the experiments, homogeneous oil-in-gelatin phantoms of different oil concentrations were fabricated to simulate different lipid-plaque concentrations. Temperature curves were recorded by a thermal couple with millisecond-level time constant. Thermal strains were computed by developed US-TSI signal processing procedures. The results build a tissue-temperature-strain model and calibrate the new US-TSI probe for in vivo atherosclerosis plaque characterization.}, number={3}, journal={JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA}, author={Sheng, Zhiyu and Wei, Ran and Chen, Mengyue and Zhang, Bohua and Kim, Howuk and Geng, Xuecang and Jiang, Xiaoning and Kim, Kang}, year={2023}, month={Mar} }
 @article{kim_zhang_wu_yao_shi_jiang_2023, title={Vortex-ultrasound for microbubble-mediated thrombolysis of retracted clots}, volume={123}, ISSN={["1077-3118"]}, url={https://doi.org/10.1063/5.0155223}, DOI={10.1063/5.0155223}, abstractNote={Endovascular sonothrombolysis has gained significant attention due to its benefits, including direct targeting of the thrombus with sonication and reduced side effects. However, the small aperture of endovascular transducers restricts the improvement of their potential clinical efficiency due to inefficient acoustic radiation. Hence, in an earlier study, we used vortex ultrasound with an endovascular ultrasound transducer to induce shear stress and enhance the clot lysis. In this study, the vortex acoustic transduction mechanism was investigated using numerical simulations and hydrophone tests. Following this characterization, we demonstrated the performance of the vortex ultrasound transducer in thrombolysis of retracted clots in in vitro tests. The test results indicated that the maximum lysis rates were 79.0% and 32.2% with the vortex ultrasound for unretracted and retracted clots, respectively. The vortex ultrasound enhanced the efficiency of the thrombolysis by approximately 49%, both for retracted and unretracted clots, compared with the typical non-vortex ultrasound technique. Therefore, the use of endovascular vortex ultrasound holds promise as a potential clinical option for the thrombolysis of retracted clots.}, number={7}, journal={APPLIED PHYSICS LETTERS}, author={Kim, Howuk and Zhang, Bohua and Wu, Huaiyu and Yao, Junjie and Shi, Chengzhi and Jiang, Xiaoning}, year={2023}, month={Aug} }
 @article{moon_wu_zhang_kim_dayton_xu_jiang_2022, title={A Dual-Frequency Intravascular Ultrasound Transducer for Amplified Nanodroplet Vaporization Effects in Cavitation-Enhanced Sonothrombolysis}, ISSN={["1948-5719"]}, DOI={10.1109/IUS54386.2022.9958578}, abstractNote={Thromboembolism often leads to stroke, myocardial infarction, and other severe complications. There remains a need for new technologies for clinical thrombosis treatment. Sonothrombolysis mediated with cavitation-enhancing agents has shown promise in the treatment of thromboembolism in preclinical studies and clinical trials. Recent works have emphasized specifically efficient sonothrombolysis using phase-change nanodroplets, likely due to their generation of cavitation within the clot matrix. Yet, it has also been reported that nanodroplets might vaporize more effectively under high-frequency excitation and generate more cavitation with low-frequency excitation. Therefore, in this work, a dual-frequency (10 MHz/500 kHz) intravascular transducer intended for nanodroplet-specific sonothrombolysis was developed to improve clot mass reduction rate while retaining lower acoustic pressures than the typical nanodroplet vaporization threshold at sub-megahertz excitation (> 5 MPa). It results in a 34 % improvement of thrombolysis efficiency compared to a single low-frequency excitation.}, journal={2022 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS)}, author={Moon, Sunho and Wu, Huaiyu and Zhang, Bohua and Kim, Jinwook and Dayton, Paul A. and Xu, Zhen and Jiang, Xiaoning}, year={2022} }
 @article{zhang_wu_jiang_2022, title={A Laser-Coupled Dual Excitation Intravascular Ultrasound Transducer for Sonothrombolysis}, ISSN={["2378-377X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85150217532&partnerID=MN8TOARS}, DOI={10.1109/NMDC46933.2022.10052561}, abstractNote={In this paper, we first introduced a miniaturized dual excitation laser-coupled intravascular ultrasound transducer with both a piezoelectric stack and a laser ultrasound transducer, which can generate a low-frequency (425 kHz) and high-frequency (7.2 MHz) dual excitation waves for thrombolysis. The prototype transducer can generate peak-negative pressure (PNP) of about 3.0 MPa with 100 Vpp input voltage and 8.5 MPa with 1mJ laser energy input, respectively. The in-vitro thrombolysis showed improved clot mass reduction (61.74 ± 3.15 %) and clot lysis speed (63.12 ± 4.35 mg/min) of dual-excitation ultrasound treatment compared to piezo or laser-generated ultrasound alone treatment.}, journal={2022 IEEE NANOTECHNOLOGY MATERIALS AND DEVICES CONFERENCE, NMDC}, author={Zhang, Bohua and Wu, Huaiyu and Jiang, Xiaoning}, year={2022}, pages={37–40} }
 @article{zhang_wu_kim_welch_cornett_stocker_nogueira_kim_owens_dayton_et al._2022, title={A Model of High-Speed Endovascular Sonothrombolysis with Vortex Ultrasound-Induced Shear Stress to Treat Cerebral Venous Sinus Thrombosis}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85146907601&partnerID=MN8TOARS}, DOI={10.1101/2022.11.02.514936}, abstractNote={Abstract This research aims to demonstrate a novel vortex ultrasound enabled endovascular thrombolysis method designed for treating cerebral venous sinus thrombosis (CVST). This is a topic of significant importance since current treatment modalities for CVST still fail in as many as 20-40% of the cases and the incidence of CVST has increased since the outbreak of the COVID-19 pandemic. Compared with conventional anticoagulant or thrombolytic drugs, sonothrombolysis has the potential to remarkably shorten the required treatment time owing to the direct clot targeting with acoustic waves. However, previously reported strategies for sonothrombolysis have not demonstrated clinically meaningful outcomes (e.g., recanalization within 30 minutes) in treating large, completely occluded veins or arteries. In this paper, we demonstrated a new vortex ultrasound technique for endovascular sonothrombolysis utilizing wave-matter interaction-induced shear stress to enhance the lytic rate substantially. Our in vitro experiment showed that the lytic rate was increased by at least 64.3 % compared with the nonvortex endovascular ultrasound treatment. A 3.1 g, 7.5 cm long, completely occluded in vitro 3D model of acute CVST was fully recanalized within 8 minutes with a record-high lytic rate of 237.5 mg/min for acute bovine clot in vitro . Furthermore, we confirmed that the vortex ultrasound causes no vessel wall damage over ex vivo bovine veins. This vortex ultrasound thrombolysis technique potentially presents a new life-saving tool for severe CVST cases that cannot be efficaciously treated using existing therapies.}, journal={bioRxiv}, author={Zhang, B. and Wu, H. and Kim, H. and Welch, P.J. and Cornett, A. and Stocker, G. and Nogueira, R.G. and Kim, J. and Owens, G. and Dayton, P. and et al.}, year={2022} }
 @article{wu_zhang_xu_huang_jiang_2022, title={A multi-directional transducer array for muscle shear wave anisotropy estimation}, ISSN={["1948-5719"]}, DOI={10.1109/IUS54386.2022.9958882}, abstractNote={Ultrasound elastography based on shear wave imaging has been widely used in clinical applications. However, the elasticity of anisotropic tissues, such as muscle and tendon, cannot be measured accurately using shear wave imaging because the shear wave velocity (SWV) varies with tissue fiber orientations. Recently, some researchers reported that anisotropic properties of muscles can be estimated by rotating the transducer for shear wave imaging. However, this approach may be difficult for clinical practices because of the relatively long data acquisition time and the misalignment errors associated with mechanical rotation of the array. Although fully sampled 2-D array can accomplish rotation electrically, the high cost and complexity of imaging hardware system can be a concern. Thus, in this work, we designed and fabricated a multi-directional transducer array in order to measure SWV for exploring the anisotropic properties of muscles. This novel star-shape transducer includes a middle element to generate acoustic radiation force for creating shear wave in tissue, and another 32 elements was alignment to form 4-element arrays for detecting the shear waves in 8 different directions (360°) without physically rotating the transducer. With a wide −6 dB bandwidth (50.9%) and high sensitivity from the receiving elements, the array showed a great potential in assessment of tissue anisotropy.}, journal={2022 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS)}, author={Wu, Huaiyu and Zhang, Bohua and Xu, Guo-Xuan and Huang, Chih-Chung and Jiang, Xiaoning}, year={2022} }
 @article{tang_wu_klippel_zhang_huang_jing_jiang_yao_2022, title={Deep thrombosis characterization using photoacoustic imaging with intravascular light delivery}, volume={12}, ISSN={["2093-985X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85124813833&partnerID=MN8TOARS}, DOI={10.1007/s13534-022-00216-0}, abstractNote={Venous thromboembolism (VTE) is a condition in which blood clots form within the deep veins of the leg or pelvis to cause deep vein thrombosis. The optimal treatment of VTE is determined by thrombus properties such as the age, size, and chemical composition of the blood clots. The thrombus properties can be readily evaluated by using photoacoustic computed tomography (PACT), a hybrid imaging modality that combines the rich contrast of optical imaging and deep penetration of ultrasound imaging. With inherent sensitivity to endogenous chromophores such as hemoglobin, multispectral PACT can provide composition information and oxygenation level in the clots. However, conventional PACT of clots relies on external light illumination, which provides limited penetration depth due to strong optical scattering of intervening tissue. In our study, this depth limitation is overcome by using intravascular light delivery with a thin optical fiber. To demonstrate in vitro blood clot characterization, clots with different acuteness and oxygenation levels were placed underneath ten-centimeter-thick chicken breast tissue and imaged using multiple wavelengths. Acoustic frequency analysis was performed on the received PA channel signals, and oxygenation level was estimated using multispectral linear spectral unmixing. The results show that, with intravascular light delivery, clot oxygenation level can be accurately measured, and the clot age can thus be estimated. In addition, we found that retracted and unretracted clots had different acoustic frequency spectrum. While unretracted clots had stronger high frequency components, retracted clots had much higher low frequency components due to densely packed red blood cells. The PACT characterization of the clots was consistent with the histology results and mechanical tests.}, number={2}, journal={BIOMEDICAL ENGINEERING LETTERS}, author={Tang, Yuqi and Wu, Huaiyu and Klippel, Paul and Zhang, Bohua and Huang, Hsiao-Ying Shadow and Jing, Yun and Jiang, Xiaoning and Yao, Junjie}, year={2022}, month={Feb} }
 @article{tang_wu_klippel_zhang_huang_jing_jiang_yao_2022, title={Deep thrombosis characterization using photoacoustic imaging with intravascular light delivery}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85133116569&partnerID=MN8TOARS}, DOI={10.21203/rs.3.rs-1312641}, journal={ResearchSquare}, author={Tang, Y. and Wu, H. and Klippel, P. and Zhang, B. and Huang, H.-Y.S. and Jing, Y. and Jiang, X. and Yao, J.}, year={2022} }
 @article{tang_wu_klippel_zhang_huang_jing_jiang_yao_2022, title={Deep thrombosis characterization using photoacoustic imaging with intravascular light delivery}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85166892380&partnerID=MN8TOARS}, DOI={10.21203/rs.3.rs-1312641/v1}, abstractNote={Abstract Venous thromboembolism (VTE) is a condition in which blood clots form within the deep veins of the leg or pelvis to cause deep vein thrombosis. The optimal treatment of VTE is determined by thrombus properties such as the age, size, and chemical composition of the blood clots. The thrombus properties can be readily evaluated by using photoacoustic computed tomography (PACT), a hybrid imaging modality that combines the rich contrast of optical imaging and deep penetration of ultrasound imaging. With inherent sensitivity to endogenous chromophores such as hemoglobin, multispectral PACT can provide composition information and oxygenation level in the clots. However, conventional PACT of clots relies on external light illumination, which provides limited penetration depth due to strong optical scattering of intervening tissue. In our study, this depth limitation is overcome by using intravascular light delivery with a thin optical fiber. To demonstrate in vitro blood clot characterization, clots with different acuteness and oxygenation levels were placed underneath ten-centimeter-thick chicken breast tissue and imaged using multiple wavelengths. Acoustic frequency analysis was performed on the received PA channel signals, and oxygenation level was estimated using multispectral linear spectral unmixing. The results show that, with intravascular light delivery, clot oxygenation level can be accurately measured, and the clot age can thus be estimated. In addition, we found that retracted and unretracted clots had different acoustic frequency spectrum. While unretracted clots had stronger high frequency components, retracted clots had much higher low frequency components due to densely packed red blood cells. The PACT characterization of the clots was consistent with the histology results and mechanical tests.}, journal={Research Square}, author={Tang, Y. and Wu, H. and Klippel, P. and Zhang, B. and Huang, H.-Y.S. and Jing, Y. and Jiang, X. and Yao, J.}, year={2022} }
 @article{xue_zhang_moon_xu_huang_sharma_jiang_2022, title={Development of a wearable ultrasound transducer for sensing muscle activities in assistive robotics applications: In vivo study}, ISSN={["1948-5719"]}, DOI={10.1109/IUS54386.2022.9958535}, abstractNote={People who suffer from the amputation of limbs or with mobility impairment due to methodological disorder sometimes require assistive robotics (AR), such as robotic prostheses and exoskeletons, to function satisfactorily and productively in daily life. Dynamic measurements of muscle voluntary activities are widely used to control AR, and sensors used to control AR should be non-invasive, effective, and wearable. Ultrasound (US) imaging is an effective method for measuring muscle activity. Nevertheless, conventional US transducers are cumbersome and inflexible, making them inconvenient for continuous monitoring of muscle activity for AR control. In light of no report available about using a flexible transducer for detecting muscle activities for AR, this work aims to develop a novel wearable US device for detecting muscle activities. In specific, a 16-element 10 MHz flexible sparse array was designed, fabricated, and characterized. The feasibility of monitoring muscle activity in different regions was demonstrated by an in vivo human experiment.}, journal={2022 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS)}, author={Xue, Xiangming and Zhang, Bohua and Moon, Sunho and Xu, Guo-Xuan and Huang, Chih-Chung and Sharma, Nitin and Jiang, Xiaoning}, year={2022} }
 @article{zhang_wu_kim_dayton_xu_jiang_2022, title={Integration of Forward-viewing and Side-viewing Ultrasound Transducers in an Intravascular Sonothrombolysis Catheter}, ISSN={["1948-5719"]}, DOI={10.1109/IUS54386.2022.9958224}, abstractNote={Thrombosis has emerged as one of the primary factors in mortality rates across the world. Conventional thrombolysis treatments for the rapid dissolution or extraction of massive thrombus, including fibrinolytic therapy and surgical thrombectomy, are time-consuming and may induce risks such as bleeding and vessel wall damage. Here we report a novel intravascular sonothrombolysis device with both forward-viewing and side-viewing elements. The developed FSV transducer prototype has a resonance frequency at 520 kHz and peak negative pressure (PNP) at 4.9 MPa (forward-viewing) and 3.2 MPa (side-viewing) under the driving voltage of 80 V pp. The combination of forward and side-viewing (FSV) ultrasound waves is expected to extend the treatment region and improve thrombolysis efficiency compared to a forward or side-viewing alone sonication.}, journal={2022 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS)}, author={Zhang, Bohua and Wu, Huaiyu and Kim, Jinwook and Dayton, Paul and Xu, Zhen and Jiang, Xiaoning}, year={2022} }
 @article{chen_kim_zhang_yang_osada_crosby_lyerly_jiang_2022, title={Intracorporeal Sonoporation-Induced Drug/Gene Delivery Using a Catheter Ultrasound Transducer}, volume={2022-October}, ISSN={["1948-5719"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85143842692&partnerID=MN8TOARS}, DOI={10.1109/IUS54386.2022.9958222}, abstractNote={Ultrasound (US) has been recently demonstrated promising in cancer immunotherapy. By virtue of microbubble-mediated cavitation, US can induce temporary pores in the cell membrane to enhance drug/gene delivery and this process is termed sonoporation. Currently, the typical US transducer for sonoporation is extracorporeal, lacking the ability to target lesions behind bones and fat efficiently, as well as to inject microbubbles (MBs) and nucleic acids into the US treatment zone simultaneously. These issues can decrease the drug/gene delivery effectiveness and increase the undesired systemic toxicity for cancer immunotherapy. Here we demonstrated an 800 kHz miniaturized US transducer for intracorporeal sonoporation-induced drug/gene delivery. Acoustic simulation using k-Wave toolbox was carried out to explore the 800 kHz US wave propagation in a 384-well cell culture plate. In-vitro sonoporation tests using human embryonic kidney (HEK) 293T cells and green fluorescent protein-luciferase (GFP-LUC) encoded plasmid DNA were conducted with various sonication parameters (i.e., 0.1 – 0.7 MPa peak-negative pressure; 20 – 2000 cycle number). The LUC assay demonstrated a significantly enhanced transfection, indicating the developed catheter transducer is promising for intracorporeal sonoporation-induced drug/gene delivery, such as intratumoral immunotherapy.}, journal={2022 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS)}, author={Chen, Mengyue and Kim, Howuk and Zhang, Bohua and Yang, Waston and Osada, Takuya and Crosby, Erika J. and Lyerly, H. Kim and Jiang, Xiaoning}, year={2022} }
 @article{chen_zhang_kim_sheng_chen_kim_geng_jiang_2022, title={Millisecond-Level Transient Temperature Monitoring Using an Ultra-Fast Response Thermocouple for Ultrasound-Induced Thermal Strain Imaging}, ISSN={["1948-5719"]}, DOI={10.1109/IUS54386.2022.9958761}, abstractNote={Ultrasound-induced thermal strain imaging (US-TSI) is promising for vulnerable atherosclerosis plaque detection. To avoid arterial motion-induced artifacts, it is needed to induce a very fast temperature rise for US-TSI. Such a short time period for a negligible tissue motion is about 1/8th of a human cardiac cycle, which is corresponding to 75 ms – 125 ms. However, the current temperature monitoring techniques, such as infrared (IR) imaging and magnetic resonance (MR) thermometry, are known with difficulty in monitoring such rapid temperature rises inside biological tissue. Herein, this paper aims to use an ultra-fast response thermocouple to observe rapid temperature rise within 50 ms. Laser-induced thermal tests were conducted in air to verify the feasibility of transient temperature monitoring. Ultrasound-induced thermal tests were conducted in biological tissue to study the influence of various sonication parameters. Obvious transient temperature rises within 50 ms can be observed for both laser tests and tissue tests. The results manifest that the proposed method is capable of monitoring transient temperature rise in biological tissue for US- TSI.}, journal={2022 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS)}, author={Chen, Mengyue and Zhang, Bohua and Kim, Howuk and Sheng, Zhiyu and Chen, Qiyang and Kim, Kang and Geng, Xuecang and Jiang, Xiaoning}, year={2022} }
 @article{zhang_wu_jiang_2022, title={Ultrasound and magnetic dual-mode stacked transducer for sonothrombolysis with a combination of nanodroplets and magnetic nanoparticles}, volume={2022-July}, ISSN={["1944-9380"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85142937501&partnerID=MN8TOARS}, DOI={10.1109/NANO54668.2022.9928649}, abstractNote={It has been observed that ultrasound thrombolysis is more effective and safer than conventional techniques of thrombolysis, such as mechanical thrombectomy or pharmaceutical medication therapies. Recent work also reported that the dual-mode excitation combining magnetic field and ultrasound helped dramatically increase the thrombolysis rate. Therefore, in this work, based on the dual-mode concept, we demonstrated a 4-element stacked transducer with a center frequency of 450 kHz, which can create ultrasonic waves in addition to a high frequency oscillating magnetic field to activate the superparamagnetic iron oxide nanoparticles (SPIONs) and nanodroplets. Under 250 Vpp input voltage, the transducer reached a peak-negative pressure of 3 MPa. The transducer can simultaneously generate ultrasound cavitation and magnetic pulse excitation, thus providing higher thrombolysis efficiency.}, journal={2022 IEEE 22ND INTERNATIONAL CONFERENCE ON NANOTECHNOLOGY (NANO)}, author={Zhang, Bohua and Wu, Huaiyu and Jiang, Xiaoning}, year={2022}, pages={71–74} }
 @article{wu_zhang_huang_peng_zhou_jiang_2022, title={Ultrasound-Guided Intravascular Sonothrombolysis With a Dual Mode Ultrasound Catheter: In Vitro Study}, volume={69}, ISSN={["1525-8955"]}, url={https://doi.org/10.1109/TUFFC.2022.3153929}, DOI={10.1109/TUFFC.2022.3153929}, abstractNote={Thromboembolism in vessels often leads to stroke or heart attack and even sudden death unless brought under control. Sonothrombolysis based on ultrasound contrast agents has shown promising outcome in effective treatment of thromboembolism. Intravascular sonothrombolysis transducer was reported recently for unprecedented sonothrombolysis <italic>in vitro</italic>. However, it is necessary to provide an imaging guide during thrombolysis in clinical applications for optimal treatment efficiency. In this article, a dual mode ultrasound catheter was developed by combining a 16-MHz high-frequency element (imaging transducer) and a 220-kHz low-frequency element (treatment transducer) for sonothrombolysis <italic>in vitro</italic>. The treatment transducer was designed with a 20-layer PZT-5A stack with the aperture size of <inline-formula> <tex-math notation="LaTeX">$1.2\times1.2$ </tex-math></inline-formula> mm<sup>2</sup>, and the imaging transducer with the aperture size of <inline-formula> <tex-math notation="LaTeX">$1.2\times1.2$ </tex-math></inline-formula> mm<sup>2</sup> was attached in front of the treatment transducer. Both transducers were assembled into a customized 2-lm 10-Fr catheter. <italic>In vitro</italic> experiment was carried out using a bovine blood clot. Imaging tests were conducted, showing that the backscattering signals can be obtained with a high signal-to-noise ratio (SNR) for the 16-MHz imaging transducer. Sonothrombolysis was performed successfully that the volume of clot was reduced significantly after the 30-min treatment. The size changes of clot were observed clearly using the 16-MHz M-mode imaging during the thrombolysis. The findings suggest that the proposed ultrasound-guided intravascular sonothrombolysis can be enhanced since the position of treatment transducer can be adjusted with the target at the clot due to the imaging guide.}, number={6}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Wu, Huaiyu and Zhang, Bohua and Huang, Chih-Chung and Peng, Chang and Zhou, Qifa and Jiang, Xiaoning}, year={2022}, month={Jun}, pages={1917–1925} }
 @article{kim_kim_wu_zhang_dayton_jiang_2021, title={A multi-pillar piezoelectric stack transducer for nanodroplet mediated intravascular sonothrombolysis}, volume={116}, ISSN={["1874-9968"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85110135734&partnerID=MN8TOARS}, DOI={10.1016/j.ultras.2021.106520}, abstractNote={We aim to develop a nanodroplet (ND)-mediated intravascular ultrasound (US) transducer for deep vein thrombosis treatments. The US device, having an efficient forward directivity of the acoustic beam, is capable of expediting the clot dissolution rate by activating cavitation of NDs injected onto a thrombus. We designed and prototyped a multi-pillar piezoelectric stack (MPPS) transducer composed of four piezoelectric stacks. Each stack was made of five layers of PZT-4 plates, having a dimension of 0.85 × 0.85 × 0.2 mm3. The transducer was characterized by measuring the electrical impedance and acoustic pressure, compared to simulation results. Next, in-vitro tests were conducted in a blood flow mimicking system using the transducer equipped with an ND injecting tube. The miniaturized transducer, having an aperture size of 2.8 mm, provided a high mechanical index of 1.52 and a relatively wide focal zone of 3.4 mm at 80 Vpp, 0.96 MHz electric input. The mass-reduction rate of the proposed method (NDs + US) was assessed to be 4.1 and 4.6 mg/min with and without the flow model, respectively. The rate was higher than that (1.3-2.7 mg/min) of other intravascular ultrasound modalities using micron-sized bubble agents. The ND-mediated intravascular sonothrombolysis using MPPS transducers was demonstrated with an unprecedented lysis rate, which may offer a new clinical option for DVT treatments. The MPPS transducer generated a high acoustic pressure (~3.1 MPa) at a distance of approximately 2.2 wavelengths from the small aperture, providing synergistic efficacy with nanodroplets for thrombolysis without thrombolytic agents.}, journal={ULTRASONICS}, author={Kim, Howuk and Kim, Jinwook and Wu, Huaiyu and Zhang, Bohua and Dayton, Paul A. and Jiang, Xiaoning}, year={2021}, month={Sep} }
 @article{chen_sheng_kim_zhang_chen_kim_geng_jiang_2021, title={Design and Simulation of Heating Transducer Arrays for Ultrasound-Induced Thermal Strain Imaging}, ISSN={["1948-5719"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85122893882&partnerID=MN8TOARS}, DOI={10.1109/IUS52206.2021.9593531}, abstractNote={Ultrasound-induced thermal strain imaging (US-TSI) has been proposed as an effective diagnostic modality for atherosclerosis plaque detection. The main challenge of current US-TSI for human subjects is the demand for a very fast temperature rise in a relatively large volume, with appropriate acoustic power that is under the Food and Drug Administration (FDA) safety limit, to cover a major artery such as carotid, and to avoid any physiologic motion artifacts. Therefore, we aim to develop heating transducer arrays with satisfied capabilities in terms of heating volume and speed for US-TSI. By virtue of using symmetrical 3.5 MHz dual 1.5D arrays and applying the dual-focus beamforming approach, the acoustic and thermal simulation results demonstrated that the designed dual heating arrays can induce a 2.1 °C temperature rise within 50 ms in a volume of 2 × 10 × 10 mm3(in terms of full width at half maximum, FWHM). The transmitting sensitivity and power conversion efficiency for a single element was estimated to be 14.1 kPa/V and 72.43%, respectively. It showed that the designed dual 1.5D heating transducer arrays can be promising for US-TSI applications.}, journal={INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS 2021)}, author={Chen, Mengyue and Sheng, Zhiyu and Kim, Howuk and Zhang, Bohua and Chen, Qiyang and Kim, Kang and Geng, Xuecang and Jiang, Xiaoning}, year={2021} }
 @article{wu_goel_kim_zhang_kim_dayton_xu_jiang_2021, title={Dual-Frequency Intravascular Sonothrombolysis: An In Vitro Study}, volume={68}, ISSN={["1525-8955"]}, url={https://doi.org/10.1109/TUFFC.2021.3103409}, DOI={10.1109/TUFFC.2021.3103409}, abstractNote={Thrombo-occlusive disease is one of the leading causes of death worldwide. There has been active research on safe and effective thrombolysis in preclinical and clinical studies. Recently, the dual-frequency transcutaneous sonothrombolysis with contrast agents [microbubbles (MBs)] has been reported to be more efficient in trigging the acoustic cavitation, which leads to a higher lysis rate. Therefore, there is increasing interest in applying dual-frequency technique for more significant efficacy improvement in intravascular sonothrombolysis since a miniaturized intravascular ultrasound transducer typically has a limited power output to fully harness cavitation effects. In this work, we demonstrated this efficacy enhancement by developing a new broadband intravascular transducer and testing dual-frequency sonothromblysis in vitro. A broadband intravascular transducer with a center frequency of 750 kHz and a footprint size of 1.4 mm was designed, fabricated, and characterized. The measured −6-dB fractional bandwidth is 68.1%, and the peak negative pressure is 1.5 MPa under the driving voltage of 80 Vpp. By keeping one frequency component at 750 kHz, the second frequency component was selected from 450 to 650 kHz with an interval of 50 kHz. The in vitro sonothrombolysis tests were conducted with a flow model and the results indicated that the MB-mediated, dual-frequency (750+500 kHz) sonothrombolysis yields an 85% higher lysis rate compared with the single-frequency treatment, and the lysis rate of dual-frequency sonothrombolysis increases with the difference between the two frequency components. These findings suggest a dual-frequency excitation technique for more efficient intravascular sonothrombolysis than conventional single-frequency excitation}, number={12}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, publisher={Institute of Electrical and Electronics Engineers (IEEE)}, author={Wu, Huaiyu and Goel, Leela D. and Kim, Howuk and Zhang, Bohua and Kim, Jinwook and Dayton, Paul A. and Xu, Zhen and Jiang, Xiaoning}, year={2021}, month={Dec}, pages={3599–3607} }
 @article{wu_kim_zhang_kim_dayton_xu_jiang_2021, title={Intravascular Dual-frequency Ultrasound Transducer Using a Stack Composite}, ISSN={["1948-5719"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85122850530&partnerID=MN8TOARS}, DOI={10.1109/IUS52206.2021.9593424}, abstractNote={Intravascular sonothrombolysis has attracted much attention due to the safe and effective treatment potential compared to other conventional mechanical thrombectomy and high-dose medication. Meanwhile, multiple frequency sonothrombolysis is known to be more efficient to activate cavitation of micro or nano size contrast agents. Yet, the multiple frequency effects combined with an intravascular device have rarely been studied in the past due to technical limitations in transmitting acoustic pressure output with multiple frequencies from a single small aperture. Therefore, in this study, an intravascular ultrasound transducer with a composite structure is reported, which can operate with the dual-frequency condition for enhancing the cavitation effect of infused contrast agents. Compared with single frequency excitation, the in-vitro test results showed a 34% improvement in the lysis rate when the dual-frequency excitation was applied with the nanodroplets infusion.}, journal={INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS 2021)}, author={Wu, Huaiyu and Kim, Howuk and Zhang, Bohua and Kim, Jinwook and Dayton, Paul and Xu, Zhen and Jiang, Xiaoning}, year={2021} }
 @article{zhang_wu_jiang_2021, title={Laser beam guided magnetic scanning catheter for sonothrombolysis with real-time clot detection}, ISSN={["1948-5719"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85122857665&partnerID=MN8TOARS}, DOI={10.1109/IUS52206.2021.9593555}, abstractNote={Thrombosis diseases have become one of the primary causes of death globally. Existing thrombolysis techniques such as using tPA (or tissue plasminogen activators) for successful dissolution of large thrombus often have a slow therapy time and complications including excessive bleeding. Besides, it is challenging to track the real-time clot location without using x-ray fluoroscopy. Here we report a novel magnetically driven scanning catheter device that integrates a stacked transducer, a tiny ring magnet, and fiber-optic laser sensors for clot spot tracking during the thrombolysis process. The magnetic scanning motion of the catheter induced by the rotational magnetic field is expected to extend the treatment region and improve thrombolysis efficiency.}, journal={INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS 2021)}, author={Zhang, Bohua and Wu, Huaiyu and Jiang, Xiaoning}, year={2021} }
 @article{zhang_wu_goel_kim_peng_kim_dayton_gao_jiang_2021, title={Magneto-sonothrombolysis with combination of magnetic microbubbles and nanodroplets}, volume={116}, ISSN={["1874-9968"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85107639068&partnerID=MN8TOARS}, DOI={10.1016/j.ultras.2021.106487}, abstractNote={This paper reports a novel technique using the rotational magnetic field oscillation and low-intensity sub-megahertz ultrasound stimulation of magnetic microbubbles (MMBs) to promote the nanodroplets (NDs) phase transition and improve the permeation of NDs into the blood clot fibrin network to enhance the sonothrombolysis efficiency. In this study, the influence of different treatment methods with a combination of MMBs and NDs on the thrombolysis rate of both unretracted and retracted clots were investigated, including the stable and inertial cavitation, tPA effects, MMBs/NDs concentration ratio, sonication factors (input voltage, duty cycle) and rotational magnetic field factors (flux density, frequency). We demonstrated that tPA-mediated magneto-sonothrombolysis in combining NDs with MMBs could significantly enhance in vitro lysis of both unretracted clots (85 ± 8.3%) and retracted clots (57 ± 6.5%) in a flow model with 30 min treatment. The results showed that the combination of MMBs and NDs substantially improves in vitro lysis of blood clots with an unprecedented lysis rate.}, journal={ULTRASONICS}, author={Zhang, Bohua and Wu, Huaiyu and Goel, Leela and Kim, Howuk and Peng, Chang and Kim, Jinwook and Dayton, Paul A. and Gao, Yu and Jiang, Xiaoning}, year={2021}, month={Sep} }
 @article{zhang_wu_jiang_2021, title={Miniaturized Dual-Mode Intravascular Transducer for Sonothrombolysis}, ISSN={["2378-377X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85125327134&partnerID=MN8TOARS}, DOI={10.1109/NMDC50713.2021.9677491}, abstractNote={Compared with traditional thrombolysis methods such as mechanical thrombectomy or pharmaceutical drug treatment, ultrasound thrombolysis has been reported to have high thrombolysis efficiency and safety. Notably, the intravascular thrombolysis with miniaturized ultrasound devices has drawn more attention due to its drug and agent delivery capability during the sonothrombolysis process. This paper presented a miniaturized dual-mode ultrasound transducer with piezoelectric stacks and a laser ultrasound transducer. By combining a low-frequency (600 kHz) tone burst sonication and a high-frequency (7.4 MHz) laser ultrasound pulse excitation, intravascular sonothrombolysis with enhanced thrombolysis was expected.}, journal={2021 IEEE 16TH NANOTECHNOLOGY MATERIALS AND DEVICES CONFERENCE (NMDC 2021)}, author={Zhang, Bohua and Wu, Huaiyu and Jiang, Xiaoning}, year={2021} }
 @article{goel_wu_zhang_kim_dayton_xu_jiang_2021, title={Nanodroplet-mediated catheter-directed sonothrombolysis of retracted blood clots}, volume={7}, ISSN={["2055-7434"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85098869774&partnerID=MN8TOARS}, DOI={10.1038/s41378-020-00228-9}, abstractNote={AbstractOne major challenge in current microbubble (MB) and tissue plasminogen activator (tPA)-mediated sonothrombolysis techniques is effectively treating retracted blood clots, owing to the high density and low porosity of retracted clots. Nanodroplets (NDs) have the potential to enhance retracted clot lysis owing to their small size and ability to penetrate into retracted clots to enhance drug delivery. For the first time, we demonstrate that a sub-megahertz, forward-viewing intravascular (FVI) transducer can be used for ND-mediated sonothrombolysis, in vitro. In this study, we determined the minimum peak negative pressure to induce cavitation with low-boiling point phase change nanodroplets and clot lysis. We then compared nanodroplet mediated sonothrombolysis to MB and tPA mediate techniques. The clot lysis as a percent mass decrease in retracted clots was 9 ± 8%, 9 ± 5%, 16 ± 5%, 14 ± 9%, 17 ± 9%, 30 ± 8%, and 40 ± 9% for the control group, tPA alone, tPA + US, MB + US, MB + tPA + US, ND + US, and ND + tPA + US groups, respectively. In retracted blood clots, combined ND- and tPA-mediated sonothrombolysis was able to significantly enhance retracted clot lysis compared with traditional MB and tPA-mediated sonothrombolysis techniques. Combined nanodroplet with tPA-mediated sonothrombolysis may provide a feasible strategy for safely treating retracted clots.}, number={1}, journal={MICROSYSTEMS & NANOENGINEERING}, author={Goel, Leela and Wu, Huaiyu and Zhang, Bohua and Kim, Jinwook and Dayton, Paul A. and Xu, Zhen and Jiang, Xiaoning}, year={2021}, month={Jan} }
 @article{goel_wu_zhang_kim_dayton_xu_jiang_2021, title={SAFETY EVALUATION OF A FORWARD-VIEWING INTRAVASCULAR TRANSDUCER FOR SONOTHROMBOLYSIS: AN IN VITRO AND EX VIVO STUDY}, volume={47}, ISSN={["1879-291X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85113414436&partnerID=MN8TOARS}, DOI={10.1016/j.ultrasmedbio.2021.07.018}, abstractNote={Recent in vitro work has revealed that a forward-viewing intravascular (FVI) transducer has sonothrombolysis applications. However, the safety of this device has yet to be evaluated. In this study, we evaluated the safety of this device in terms of tissue heating, vessel damage and particle debris size during sonothrombolysis using microbubbles or nanodroplets with tissue plasminogen activator, in both retracted and unretracted blood clots. The in vitro and ex vivo sonothrombolysis tests using FVI transducers revealed a temperature rise of less than 1°C, no vessel damage as assessed by histology and no downstream clot particles >500 µm. These in vitro and ex vivo results indicate that the FVI transducer poses minimal risk for sonothrombolysis applications and should be further evaluated in animal models.}, number={11}, journal={ULTRASOUND IN MEDICINE AND BIOLOGY}, author={Goel, Leela and Wu, Huaiyu and Zhang, Bohua and Kim, Jinwook and Dayton, Paul A. and Xu, Zhen and Jiang, Xiaoning}, year={2021}, month={Nov}, pages={3231–3239} }
 @article{peng_zhang_wu_dayton_xu_jiang_2021, title={Ultrasound Imaging-Guided Microbubble-Mediated Catheter-Directed Sonothrombolysis: An In-Vitro Study}, ISSN={["2378-377X"]}, DOI={10.1109/NMDC50713.2021.9677506}, abstractNote={Summary form only given, as follows. The complete presentation was not made available for publication as part of the conference proceedings. Deep vein thrombosis (DVT) is the formation of a blood clot in a deep vein, usually in the lower leg or thigh. The most serious complication of DVT is pulmonary embolism, which happens when part of the blood clot breaks off and travels through the bloodstream to the lungs, suddenly blocking blood flow. While using clot dissolving drugs is the standard treatment for DVT, thrombolytic drugs illustrate low thrombolysis efficiency and risk of bleeding side effects. Catheter-directed thrombolysis that uses a catheter to guide medication or a medical device to the site of a blood clot to dissolve the blockage, has become one of the most widely available and effective treatments for DVT. In this study, we combine a catheter-delivered forward-looking ultrasound transducer with microbubbles for microbubble-mediated catheter-directed sonothrombolysis, in order to reduce treatment time and increase treatment efficacy. A 600 kHz stack ultrasound transducer is developed and integrated into one lumen of an 8 Fr two-lumen catheter. During the sonothrombolysis procedure, the catheter location relative to the thrombus within a blood vessel is monitoring using ultrasound imaging guidance; the catheter tip distance to the blood clot is continuously controlled via a micro linear actuator with a speed of 100 μm/min.}, journal={2021 IEEE 16TH NANOTECHNOLOGY MATERIALS AND DEVICES CONFERENCE (NMDC 2021)}, author={Peng, Chang and Zhang, Bohua and Wu, Huaiyu and Dayton, Paul and Xu, Zhen and Jiang, Xiaoning}, year={2021} }
 @article{zhang_wu_jiang_2021, title={Ultrasound and Magnetic Dual-Mode Stacked Transducer for High-Frequency Magneto- Sonothrombolysis}, ISSN={["2378-377X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85125334509&partnerID=MN8TOARS}, DOI={10.1109/NMDC50713.2021.9677479}, abstractNote={Thrombosis usually occurs when a blood clot shapes within the blood vessel which may prevent the bloodstream through the body. Earlier microbubbles and tPA-mediated ultrasound thrombolysis usually had a relatively low efficacy for retracted clots owing to the limited penetration of agents into the condensed clot fibrin networks. Here we report the advancement of ultrasound and magnetic dual-mode stacked transducers, which can generate ultrasound wave and high frequency oscillating magnetic field to stimulate the superparamagnetic iron oxide nanoparticles (SPIONs) and microbubbles for enhanced tPA-mediated sonothrombolysis. The results showed that the combined effects of localized hyperthermia from the high-frequency oscillation of SPIONs and mechanical shock waves from ultrasound could effectively enhance the tPA-mediated sonothrombolysis efficacy.}, journal={2021 IEEE 16TH NANOTECHNOLOGY MATERIALS AND DEVICES CONFERENCE (NMDC 2021)}, author={Zhang, Bohua and Wu, Huaiyu and Jiang, Xiaoning}, year={2021} }
 @inproceedings{wu_goel_zhang_kim_dayton_xu_jiang_2020, title={Dual-frequency intravascular thrombolysis with miniaturized forward-looking transducers}, volume={2020-September}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85097866206&partnerID=MN8TOARS}, DOI={10.1109/IUS46767.2020.9251664}, abstractNote={Thrombo-occlusive disease is one of the leading causes of death worldwide, which primarily arise from blood clot formation in deep veins. However, the existing treatment methods, including mechanical thrombectomy and pharmaceutical drug treatment usually suffer from potential risk of blood vessel damages and long treatment times. Recently, ultrasound-enhanced thrombolysis (ie sonothrombolysis) has been actively investigated due to its relatively high efficiency and safety compared to thrombolytic treatment alone. Dual frequency sonothrombolysis may improve existing single frequency sonothrombolysis techniques. Notably, when the same power is applied, the dual-frequency sonothrombolysis has been reported to be more efficient due to its relatively higher peak-negative pressure compared with single-frequency treatment. However, there is no report on dual frequency sonothombolysis using intravascular transducers. Moreover, there is a lack of sonothrombolysis comparison with different frequency combinations. Therefore, in this work, the effect of dual-frequency treatment on the intravascular thrombolysis was investigated with under various frequency combinations. The results indicated that the dual-frequency treatment had a 18% higher thrombolysis rate with an increasing trend when the difference between two frequency components increased.}, booktitle={IEEE International Ultrasonics Symposium, IUS}, author={Wu, H. and Goel, L. and Zhang, B. and Kim, J. and Dayton, P. and Xu, Z. and Jiang, X.}, year={2020} }
 @article{goel_wu_kim_zhang_kim_dayton_xu_jiang_2020, title={EXAMINING THE INFLUENCE OF LOW-DOSE TISSUE PLASMINOGEN ACTIVATOR ON MICROBUBBLE-MEDIATED FORWARD-VIEWING INTRAVASCULAR SONOTHROMBOLYSIS}, volume={46}, ISSN={["1879-291X"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85086524519&partnerID=MN8TOARS}, DOI={10.1016/j.ultrasmedbio.2020.03.012}, abstractNote={Previous work revealed that a forward-viewing intravascular (FVI) transducer can be used for microbubble (MB)-mediated sonothrombolysis and that the clot lysis was dependent on MB concentration. This study examined the effects of combining tissue plasminogen activator (tPA) with MB-mediated FVI sonothrombolysis. In vitro clot lysis and passive cavitation experiments were conducted to study the effect of low-dose tPA in FVI sonothrombolysis with varying MB concentrations. Enhanced FVI sonothrombolysis was observed in cases in which ultrasound (US) was combined with tPA or MBs compared with control, tPA alone or US alone. The lysis rate of US + tPA + MBs was improved by up to 130%, 31% and 8% for MB concentrations of 106, 107 and 108 MBs/mL, respectively, compared with MBs + US alone. Changes in stable and inertial cavitation doses were observed, corresponding to changes in clot lysis in MB-mediated FVI sonothrombolysis with and without tPA.}, number={7}, journal={ULTRASOUND IN MEDICINE AND BIOLOGY}, author={Goel, Leela and Wu, Huaiyu and Kim, Howuk and Zhang, Bohua and Kim, Jinwook and Dayton, Paul A. and Xu, Zhen and Jiang, Xiaoning}, year={2020}, month={Jul}, pages={1698–1706} }
 @inproceedings{zhang_wu_goel_jiang_2020, title={Laser Sensor Guided Intravascular Catheter with Ring Type Stack Transducer for Sonothrombolysis}, volume={2020-September}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85097890919&partnerID=MN8TOARS}, DOI={10.1109/IUS46767.2020.9251671}, abstractNote={Thrombosis diseases have become a leading cause of mortality worldwide. Current treatment methods such as thrombolytic drugs or mechanical thrombectomy for effective removal or dissolution of large blood clots often suffer from a long treatment time and potential hemorrhage. Moreover, it is difficult to detect the clot position during the treatment. Here we report the development of a novel sonothrombolysis catheter device that incorporates a ring-type stack transducer and optical fiber-based laser sensor for clot detection and treatment. The developed transducer has a center frequency at 340 kHz and peak negative pressure (PNP) at 1.87 MPa with 120 Vpp input voltage, which is high enough for triggering cavitation of the agents. The measured beam profile indicates a natural beam focus at 2.8 mm from the transducer. The in vitro MBs and NDs-mediated sonothrombolysis tests showed about two-fold significantly improved lysis rate for both unretracted and retracted clot compare to the control group.}, booktitle={IEEE International Ultrasonics Symposium, IUS}, author={Zhang, B. and Wu, H. and Goel, L. and Jiang, X.}, year={2020} }
 @inproceedings{goel_wu_zhang_kim_dayton_xu_jiang_2020, title={Nanodroplet mediated intravascular sonothrombolysis of retracted clots}, volume={2020-September}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85097906427&partnerID=MN8TOARS}, DOI={10.1109/IUS46767.2020.9251699}, abstractNote={Current sonothrombolysis techniques have limited efficacy for treating retracted clots. Nanodroplet (ND) mediated sonothrombolysis has the potential to facilitate tPA penetration into the dense fibrin networks of retracted clots via nanodroplet-induced cavitation. Intravascular sonothrombolysis is of interest to improve catheter directed clot treatments and mitigate off-target effects. This paper investigates the feasibility of nanodroplet-mediated sonothrombolysis with tPA to treat retracted clots, in vitro, using a forward-viewing intravascular transducer. The percent mass decrease of the retracted clots (mean ± std) were 4 ± 2%, 20 ± 3%, 23 ± 5%, 38 ± 9% for the control, tPA + US, ND + US, and ND + tPA + US groups, respectively. All of the sonothrombolysis conditions resulted in statistically significantly higher clot lysis compared to the control group (p<0.05). The combined ND + tPA + US treatment significantly outperformed the ND + US condition (p<0.05) and approached significance for the tPA + US group (p = 0.09). In summary, our forward-viewing intravascular transducer was demonstrated, for the first time, for sonothrombolysis in a retracted clot model by combining NDs and tPA.}, booktitle={IEEE International Ultrasonics Symposium, IUS}, author={Goel, L. and Wu, H. and Zhang, B. and Kim, J. and Dayton, P. and Xu, Z. and Jiang, X.}, year={2020} }
 @inproceedings{goel_wu_zhang_kim_dayton_xu_jiang_2020, title={Nanodroplet-mediated intravascular sonothrombolysis: Cavitation study}, volume={2020-July}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85091042701&partnerID=MN8TOARS}, DOI={10.1109/NANO47656.2020.9183421}, abstractNote={Nanodroplets mediated sonothrombolysis has the potential to improve thrombolytic outcomes and minimize the need for thrombolytic drugs. Our group has developed a forward-viewing intravascular transducer which can perform contrast agent mediated sonothrombolysis. Most applications of nanodroplets mediated sonothrombolysis are applied by an external transducer, which cannot access locations blocked by bones or gassy organs, thus greatly limiting its usage. The purpose of our study was to demonstrate the feasibility of using nanodroplets with our small aperture intravascular transducers, which would allow access to a wide range of locations. Passive cavitation detection was performed to determine the minimum peak negative pressure output necessary for nanodroplet mediated sonothrombolysis and initial clot lysis tests were performed. The stable cavitation dose increased with increasing peak negative pressure output, with there being a higher stable cavitation dose at 0.9 MPa and 1.2 MPa compared to controls. The inertial cavitation dose was higher at 0.6 and 0.9 MPa compared to the control group. In our proof-of-concept demonstration, nanodroplets mediated sonothrombolysis presented a mass decrease of 55 ± 1% compared to 29 ± 6% for the control group (p=0.02). We demonstrated that it was feasible to deliver nanodroplet mediated sonothrombolysis using the small aperture intravascular transducers.}, booktitle={Proceedings of the IEEE Conference on Nanotechnology}, author={Goel, L. and Wu, H. and Zhang, B. and Kim, J. and Dayton, P.A. and Xu, Z. and Jiang, X.}, year={2020}, pages={185–188} }
 @inproceedings{goel_wu_kim_zhang_kim_dayton_xu_jiang_2019, title={Intravascular Sonothrombolysis, in vitro, Using a Small Aperture, Forward-Viewing, Sub-Megahertz Transducer to Enhance tPA Treatment}, volume={2019-October}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85077636041&partnerID=MN8TOARS}, DOI={10.1109/ULTSYM.2019.8926028}, abstractNote={Catheter-based thrombolytic treatments with tissue plasminogen activator (tPA) have long treatment times (>15 hrs) and high risk of intracranial hemorrhage. Sonothrombolysis may improve patient outcomes while reducing the dose of tPA needed for treatment. We recently demonstrated a custom, forward-viewing intravascular (FVI) transducer with microbubbles (MBs) for in vitro sonothrombolysis. For clinical translation, we want to utilize this transducer to enhance tPA treatment. Therefore, the purpose of this study was to examine the thrombolytic outcomes of a forward-looking, IV transducer with tPA in vitro. Blood clots were treated for 30 minutes with either phosphate buffer saline (PBS), ultrasound (US) alone, tPA alone (1µg/ml), tPA + US, or MB + US (108 MB/ml). The percent clot lysis for the control group was 29 ± 4%, tPA alone was 29 ± 9%, and US alone was 25 ± 4%, with no statistically significant differences amongst these conditions. The percent clot lysis was 58 ± 10%, 59 ± 3% and 63 ± 5% for tPA + US and MB + US conditions respectively and both had statistically significantly more clot lysis than the control, US alone, or tPA alone groups. We have demonstrated that a forward-viewing intravascular transducer can be used to enhance tPA mediated sonothrombolysis and is comparable to microbubble mediated sonothrombolysis.}, booktitle={IEEE International Ultrasonics Symposium, IUS}, author={Goel, L. and Wu, H. and Kim, H. and Zhang, B. and Kim, J. and Dayton, P. and Xu, Z. and Jiang, X.}, year={2019}, pages={2034–2036} }
 @article{zhang_kim_wu_gao_jiang_2019, title={Sonothrombolysis with magnetic microbubbles under a rotational magnetic field}, volume={98}, ISSN={["1874-9968"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85067191804&partnerID=MN8TOARS}, DOI={10.1016/j.ultras.2019.06.004}, abstractNote={Thrombosis is an extremely critical clinical condition where a clot forms inside a blood vessel which blocks the blood flow through the cardiovascular system. Previous sonothrombolysis methods using ultrasound and microbubbles (MBs) often have a relatively low lysis rate due to the low microbubbles concentration at clot region caused by blood flow in the vessel. To solve this problem, the magnetic microbubbles (MMBs) that can be retained by an outer magnetic field against blood flow are used in this study. Here we report the development of a new method using the rotational magnetic field to trap and vibrate magnetic microbubbles at target clot region and then using an intravascular forward-looking ultrasound transducer to activate them acoustically. In this study, we investigated the influence of different blood flow conditions, vessel occlusion conditions (partial and fully occluded), clot ages (fresh, retracted), ultrasound parameters (input voltage, duty cycle) and rotational magnetic field parameters (amplitude, frequency) on the thrombolysis rate. The results showed that the additional use of magnetic microbubbles significantly enhances in vitro lysis of blood clot.}, journal={ULTRASONICS}, author={Zhang, Bohua and Kim, Howuk and Wu, Huaiyu and Gao, Yu and Jiang, Xiaoning}, year={2019}, month={Sep}, pages={62–71} }
 @inproceedings{zhang_jiang_wu_2019, title={Ultrasound thrombolysis with magnetic microbubbles under a rotational magnetic field}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85061773298&partnerID=MN8TOARS}, DOI={10.1109/NMDC.2018.8605856}, abstractNote={Thrombosis is a severe clinical condition that blood clot forms in a blood vessel and blocks the flow of blood through the cardiovascular system. Previous ultrasound thrombolysis methods using microbubbles often have a relatively low lysis efficiency due to the low microbubble concentration at clot region caused by blood flow in the vessel. To solve this problem, the magnetic microbubbles (microbubbles coated with 50 nm magnetic nanoparticles) that can be manipulated by a magnetic field are introduced in the study. The rationale of this study was to investigate whether magnetic microbubble can be a useful adjuvant to improve the sonothrombolysis treatment efficiency. Here we report the development of a new method using the rotational magnetic field to trap and vibrate the magnetic microbubbles at target clot region and then using an intravascular forward-looking ultrasound transducer to activate them acoustically. The in-vitro intravascular sonothrombolysis testing results indicated that by oscillating magnetic microbubbles, a vortex-like microstreaming in clot region will enhance microbubble cavitation and exhibit a higher lysis rate (1.5 $\pm$ 0.06%/min) than the previous (0.7 $\pm$ 0.15%/min)microbubble alone sonothrombolysis technique.}, booktitle={2018 IEEE 13th Nanotechnology Materials and Devices Conference, NMDC 2018}, author={Zhang, B. and Jiang, X. and Wu, H.}, year={2019} }