Publications by authors named "Bohua Zhang"

7 Publications

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Safety Evaluation of a Forward-Viewing Intravascular Transducer for Sonothrombolysis: An in Vitro and ex Vivo Study.

Ultrasound Med Biol 2021 Aug 23. Epub 2021 Aug 23.

Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, North Carolina, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2021.07.018DOI Listing
August 2021

Dual-Frequency Intravascular Sonothrombolysis: an In-vitro Study.

IEEE Trans Ultrason Ferroelectr Freq Control 2021 Aug 9;PP. Epub 2021 Aug 9.

Thrombo-occlusive disease is one of the leading causes of death worldwide. There has been active research on safe and effective thrombolysis in pre-clinical and clinical studies. Recently, the dual-frequency transcutaneous sonothrombolysis with contrast agents (microbubbles) 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 effiacy 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 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 kHz 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 microbubble-mediated, dual-frequency (750 kHz + 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.
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http://dx.doi.org/10.1109/TUFFC.2021.3103409DOI Listing
August 2021

A multi-pillar piezoelectric stack transducer for nanodroplet mediated intravascular sonothrombolysis.

Ultrasonics 2021 Jul 9;116:106520. Epub 2021 Jul 9.

The Department of Mechanical and Aerospace Engineering at North Carolina State University, Raleigh, NC 27695, USA. Electronic address:

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 mm. 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 V, 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.
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http://dx.doi.org/10.1016/j.ultras.2021.106520DOI Listing
July 2021

Magneto-sonothrombolysis with combination of magnetic microbubbles and nanodroplets.

Ultrasonics 2021 Jun 6;116:106487. Epub 2021 Jun 6.

Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ultras.2021.106487DOI Listing
June 2021

Nanodroplet-mediated catheter-directed sonothrombolysis of retracted blood clots.

Microsyst Nanoeng 2021 6;7. Epub 2021 Jan 6.

Department of Mechanical & Aerospace Engineering, North Carolina State University, Raleigh, NC 27695 USA.

One 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.
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http://dx.doi.org/10.1038/s41378-020-00228-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787976PMC
January 2021

Examining the Influence of Low-Dose Tissue Plasminogen Activator on Microbubble-Mediated Forward-Viewing Intravascular Sonothrombolysis.

Ultrasound Med Biol 2020 07 7;46(7):1698-1706. Epub 2020 May 7.

Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, North Carolina, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2020.03.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293952PMC
July 2020

Sonothrombolysis with magnetic microbubbles under a rotational magnetic field.

Ultrasonics 2019 Sep 10;98:62-71. Epub 2019 Jun 10.

Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh 27695, NC, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.ultras.2019.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6710138PMC
September 2019
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