@article{dauba_spitzlei_bautista_jourdain_selingue_vantreeck_mattern_denis_ouldali_arteni_et al._2024, title={Low-boiling-point perfluorocarbon nanodroplets for adaptable ultrasound-induced blood-brain barrier opening}, volume={376}, ISSN={["1873-4995"]}, DOI={10.1016/j.jconrel.2024.10.023}, abstractNote={Low-boiling point perfluorocarbon nanodroplets (NDs) are valued as effective sonosensitive agents, encapsulating a liquid perfluorocarbon that would instantaneously vaporize at body temperature without the NDs shell. Those NDs have been explored for both therapeutic and diagnostic purposes. Here, phospholipid-shelled nanodroplets containing octafluoropropane (C3F8) or decafluorobutane (C4F10) formed by condensation of microbubbles were thoroughly characterized before blood-brain (BBB) permeabilization. Transmission electron microscopy (TEM) and cryo-TEM were employed to confirm droplet formation while providing high-resolution insights into the droplet surface and lipid arrangement assessed from electron density observation after condensation. The vaporization threshold of NDs was determined with a high-speed camera, and the frequency signal emitted by the freshly vaporized bubbles was analyzed using cavitation detection. C3F8 NDs exhibited vaporization at 0.3 MPa (f0 = 1.5 MHz, 50 cycles), and emitted signals at 2 f0 and 1.5 f0 from 0.45 MPa onwards (f0 = 1.5 MHz, 50 cycles), while broadband noise was measured starting from 0.55 MPa. NDs with the higher boiling point C4F10 vaporized at 1.15 MPa and emitted signals at 2 f0 from 0.65 MPa and 1.5 f0 from 0.9 MPa, while broadband noise was detected starting from 0.95 MPa. Both ND formulations were used to permeabilize the BBB in healthy mice using tailored ultrasound sequences, allowing for the identification of optimal applications for each NDs type. C3F8 NDs proved suitable and safe for permeabilizing a large area, potentially the entire brain, at low acoustic pressure. Meanwhile, C4F10 droplets facilitated very localized (400 μm isotropic) permeabilization at higher pressure. This study prompts a closer examination of the structural rearrangements occurring during the condensation of microbubbles into NDs and highlights the potential to tailor solutions for different brain pathologies by choosing the composition of the NDs and adjusting the ultrasound sequence.}, journal={JOURNAL OF CONTROLLED RELEASE}, author={Dauba, Ambre and Spitzlei, Claire and Bautista, Kathlyne Jayne B. and Jourdain, Laurene and Selingue, Erwan and Vantreeck, Kelly E. and Mattern, Jacob A. and Denis, Caroline and Ouldali, Malika and Arteni, Ana-Andreea and et al.}, year={2024}, month={Dec}, pages={441–456} } @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}, volume={42}, ISSN={2095-8099}, url={http://dx.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}, publisher={Elsevier BV}, 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={Nov}, pages={235–243} } @misc{bautista_kim_xu_jiang_dayton_2023, title={Current Status of Sub-micron Cavitation-Enhancing Agents for Sonothrombolysis}, volume={49}, ISSN={["1879-291X"]}, DOI={10.1016/j.ultrasmedbio.2023.01.018}, abstractNote={Thrombosis in cardiovascular disease is an urgent global issue, but treatment progress is limited by the risks of current antithrombotic approaches. The cavitation effect in ultrasound-mediated thrombolysis offers a promising mechanical alternative for clot lysis. Further addition of microbubble contrast agents introduces artificial cavitation nuclei that can enhance the mechanical disruption induced by ultrasound. Recent studies have proposed sub-micron particles as novel sonothrombolysis agents with increased spatial specificity, safety and stability for thrombus disruption. In this article, the applications of different sub-micron particles for sonothrombolysis are discussed. Also reviewed are in vitro and in vivo studies that apply these particles as cavitation agents and as adjuvants to thrombolytic drugs. Finally, perspectives on future developments in sub-micron agents for cavitation-enhanced sonothrombolysis are shared. Thrombosis in cardiovascular disease is an urgent global issue, but treatment progress is limited by the risks of current antithrombotic approaches. The cavitation effect in ultrasound-mediated thrombolysis offers a promising mechanical alternative for clot lysis. Further addition of microbubble contrast agents introduces artificial cavitation nuclei that can enhance the mechanical disruption induced by ultrasound. Recent studies have proposed sub-micron particles as novel sonothrombolysis agents with increased spatial specificity, safety and stability for thrombus disruption. In this article, the applications of different sub-micron particles for sonothrombolysis are discussed. Also reviewed are in vitro and in vivo studies that apply these particles as cavitation agents and as adjuvants to thrombolytic drugs. Finally, perspectives on future developments in sub-micron agents for cavitation-enhanced sonothrombolysis are shared.}, number={5}, journal={ULTRASOUND IN MEDICINE AND BIOLOGY}, author={Bautista, Kathlyne Jayne B. and Kim, Jinwook and Xu, Zhen and Jiang, Xiaoning and Dayton, Paul A.}, year={2023}, month={May}, pages={1049–1057} } @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={0885-3010 1525-8955}, url={http://dx.doi.org/10.1109/TUFFC.2021.3137125}, 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/cm}, number={2}, journal={IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control}, publisher={Institute of Electrical and Electronics Engineers (IEEE)}, 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{belekov_bautista_annayev_adelegan_biliroglu_kierski_sanders_kemal_sennik_yamaner_et al._2022, title={Performance Assessment of Ultra-Wideband and Dual-Mode 1D CMUT Arrays for Acoustic Angiography}, ISSN={["1948-5719"]}, DOI={10.1109/IUS54386.2022.9958537}, abstractNote={In this work, we have demonstrated the imaging potential of 256-element ultra-wideband (UWB) and dual-mode CMUT 1D arrays for acoustic angiography through mechanical index measurements and in-vitro imaging experiments. We have designed a custom 256-channel imaging probe with integrated low-noise amplifiers and supporting power circuitry. To improve the elevational focusing, we mounted an acoustic lens on to the array. The acoustic characterization of the CMUT array was performed by a calibrated hydrophone, with which we measured sufficiently high mechanical indices (i.e., 0.79 MI for the UWB and 0.85 MI for the dual-mode array) at the focal spot at 15-mm depth. We conducted an imaging experiment with a tissue-mimicking phantom including a 0.2-mm-diameter cellulose tube, in which microbubbles and water flowed. We demonstrated a CTR of 62.12 ± 1.06 dB for the UWB array and a CTR of 59.69 ± 0.39 dB for the dual-mode array when microbubbles were flowing through the tube. These experiments presented a strong use case for the UWB and dual-mode CMUT arrays in acoustic angiography applications.}, journal={2022 IEEE INTERNATIONAL ULTRASONICS SYMPOSIUM (IEEE IUS)}, author={Belekov, Ermek and Bautista, Kathlyne J. and Annayev, Muhammetgeldi and Adelegan, Oluwafemi J. and Biliroglu, Ali O. and Kierski, Thomas M. and Sanders, Jean L. and Kemal, Remzi E. and Sennik, Erdem and Yamaner, Feysel Y. and et al.}, year={2022} }