@article{kim_bautista_deruiter_goel_jiang_xu_dayton_2022, title={An Analysis of Sonothrombolysis and Cavitation for Retracted and Unretracted Clots Using Microbubbles Versus Low-Boiling-Point Nanodroplets}, volume={69}, ISSN={["1525-8955"]}, DOI={10.1109/TUFFC.2021.3137125}, abstractNote={The thrombolysis potential of low-boiling-point (−2 °C) perfluorocarbon phase-change nanodroplets (NDs) has previously been demonstrated on aged clots, and we hypothesized that this efficacy would extend to retracted clots. We tested this hypothesis by comparing sonothrombolysis of both unretracted and retracted clots using ND-mediated ultrasound (US+ND) and microbubble-mediated ultrasound (US+MB), respectively. Assessment data included clot mass reduction, cavitation detection, and cavitation cloud imaging in vitro. Acoustic parameters included a 7.9-MPa peak negative pressure and 180-cycle bursts with 5-Hz repetition (the corresponding duty cycle and time-averaged intensity of 0.09% and 1.87 W/cm2, respectively) based on prior studies. With these parameters, we observed a significantly reduced efficacy of US+MB in the retracted versus unretracted model (the averaged mass reduction rate from 1.83%/min to 0.54%/min). Unlike US+MB, US+ND exhibited less reduction of efficacy in the retracted model (from 2.15%/min to 1.04%/min on average). The cavitation detection results correlate with the sonothrombolysis efficacy results showing that both stable and inertial cavitation generated in a retracted clot by US+ND is higher than that by US+MB. We observed that ND-mediated cavitation shows a tendency to occur inside a clot, whereas MB-mediated cavitation occurs near the surface of a retracted clot, and this difference is more significant with retracted clots compared to unretracted clots. We conclude that ND-mediated sonothrombolysis outperforms MB-mediated therapy regardless of clot retraction, and this advantage of ND-mediated cavitation is emphasized for retracted clots. The primary mechanisms are hypothesized to be sustained cavitation level and cavitation clouds in the proximity of a retracted clot by US+ND.}, number={2}, journal={IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL}, author={Kim, Jinwook and Bautista, Kathlyne Jayne B. and Deruiter, Ryan M. and Goel, Leela and Jiang, Xiaoning and Xu, Zhen and Dayton, Paul A.}, year={2022}, month={Feb}, pages={711–719} }
 @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{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{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={Abstract}, 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{kim_deruiter_goel_xu_jiang_dayton_2020, title={A COMPARISON OF SONOTHROMBOLYSIS IN AGED CLOTS BETWEEN LOWBOILING-POINT PHASE-CHANGE NANODROPLETS AND MICROBUBBLES OF THE SAME COMPOSITION}, volume={46}, ISSN={["1879-291X"]}, DOI={10.1016/j.ultrasmedbio.2020.07.008}, abstractNote={We present enhanced cavitation erosion of blood clots exposed to low-boiling-point (−2°C) perfluorocarbon phase-change nanodroplets and pulsed ultrasound, as well as microbubbles with the same formulation under the same conditions. Given prior success with microbubbles as a sonothrombolysis agent, we considered that perfluorocarbon phase-change nanodroplets could enhance clot disruption further beyond that achieved with microbubbles. It has been hypothesized that owing to their small size and ability to penetrate into a clot, nanodroplets could enhance cavitation inside a blood clot and increase sonothrombolysis efficacy. The thrombolytic effects of lipid-shell-decafluorobutane nanodroplets were evaluated and compared with those of microbubbles with the same formulation, in an aged bovine blood clot flow model. Seven different pulsing schemes, with an acoustic intensity (ISPTA) range of 0.021–34.8 W/cm2 were applied in three different therapy scenarios: ultrasound only, ultrasound with microbubbles and ultrasound with nanodroplets (n = 5). Data indicated that pulsing schemes with 0.35 W/cm2 and 5.22 W/cm2 produced a significant difference (p < 0.05) in nanodroplet sonothrombolysis performance compared with compositionally identical microbubbles. With these excitation conditions, nanodroplet-mediated treatment achieved a 140% average thrombolysis rate over the microbubble-mediated case. We observed distinctive internal erosion in the middle of bovine clot samples from nanodroplet-mediated ultrasound, whereas the microbubble-mediated case generated surface erosion. This erosion pattern was supported by ultrasound imaging during sonothrombolysis, which revealed that nanodroplets generated cavitation clouds throughout a clot, whereas microbubble cavitation formed larger cavitation clouds only outside a clot sample.}, number={11}, journal={ULTRASOUND IN MEDICINE AND BIOLOGY}, author={Kim, Jinwook and DeRuiter, Ryan M. and Goel, Leela and Xu, Zhen and Jiang, Xiaoning and Dayton, Paul A.}, year={2020}, month={Nov}, pages={3059–3068} }
 @misc{goel_jiang_2020, title={Advances in Sonothrombolysis Techniques Using Piezoelectric Transducers}, volume={20}, ISSN={["1424-8220"]}, DOI={10.3390/s20051288}, abstractNote={One of the great advancements in the applications of piezoelectric materials is the application for therapeutic medical ultrasound for sonothrombolysis. Sonothrombolysis is a promising ultrasound based technique to treat blood clots compared to conventional thrombolytic treatments or mechanical thrombectomy. Recent clinical trials using transcranial Doppler ultrasound, microbubble mediated sonothrombolysis, and catheter directed sonothrombolysis have shown promise. However, these conventional sonothrombolysis techniques still pose clinical safety limitations, preventing their application for standard of care. Recent advances in sonothrombolysis techniques including targeted and drug loaded microbubbles, phase change nanodroplets, high intensity focused ultrasound, histotripsy, and improved intravascular transducers, address some of the limitations of conventional sonothrombolysis treatments. Here, we review the strengths and limitations of these latest pre-clincial advancements for sonothrombolysis and their potential to improve clinical blood clot treatments.}, number={5}, journal={SENSORS}, author={Goel, Leela and Jiang, Xiaoning}, year={2020}, month={Mar} }
 @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} }