Thomas R Porter1, Christopher Arena2, Samer Sayyed2, John Lof2, Robin R High2, Feng Xie2, Paul A Dayton2. 1. From the Department of Internal Medicine, University of Nebraska Medical Center, Omaha (T.R.P., S.S., J.L., R.R.H., F.X.); Department of Engineering, Elon University, NC (C.A.); and Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University (P.A.D.). trporter@unmc.edu. 2. From the Department of Internal Medicine, University of Nebraska Medical Center, Omaha (T.R.P., S.S., J.L., R.R.H., F.X.); Department of Engineering, Elon University, NC (C.A.); and Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University (P.A.D.).
Abstract
BACKGROUND: Liquid core nanodroplets containing condensed gaseous fluorocarbons can be vaporized at clinically relevant acoustic energies and have been hypothesized as an alternative ultrasound contrast agent instead of gas-core agents. The potential for targeted activation and imaging of these agents was tested with droplets formulated from liquid octafluoropropane (C3) and 1:1 mixtures of C3 with liquid decafluorobutane (C3C4). METHODS AND RESULTS: In 8 pigs with recent myocardial infarction and variable degrees of reperfusion, transthoracic acoustic activation was attempted using 1.3 to 1.7 MHz low (0.2 mechanical index [MI]) or high MI (1.2 MI) imaging in real time (32-64 Hertz) or triggered 1:1 at end systole during a 20% C3 or C3C4 droplet infusion. Any perfusion defects observed were measured and correlated with delayed enhancement magnetic resonance imaging and postmortem staining. No myocardial contrast was produced with any imaging setting when using C3C4 droplets or C3 droplets during low MI real-time imaging. However, myocardial contrast was observed in all 8 pigs with C3 droplets when using triggered high MI imaging and in 5 of 6 pigs that had 1.7 MHz real time-high MI imaging. Although quantitative myocardial contrast was lower with real-time high MI imaging than 1:1 triggering, the correlation between real-time resting defect size and infarct size was good (r=0.97; P<0.001), as was the correlation with number of transmural infarcted segments by delayed enhancement imaging. CONCLUSIONS: Targeted transthoracic acoustic activation of infused intravenous C3 nanodroplets is effective, resulting in echogenic and persistent microbubbles which provide real-time high MI visualization of perfusion defects.
BACKGROUND: Liquid core nanodroplets containing condensed gaseous fluorocarbons can be vaporized at clinically relevant acoustic energies and have been hypothesized as an alternative ultrasound contrast agent instead of gas-core agents. The potential for targeted activation and imaging of these agents was tested with droplets formulated from liquid octafluoropropane (C3) and 1:1 mixtures of C3 with liquid decafluorobutane (C3C4). METHODS AND RESULTS: In 8 pigs with recent myocardial infarction and variable degrees of reperfusion, transthoracic acoustic activation was attempted using 1.3 to 1.7 MHz low (0.2 mechanical index [MI]) or high MI (1.2 MI) imaging in real time (32-64 Hertz) or triggered 1:1 at end systole during a 20% C3 or C3C4 droplet infusion. Any perfusion defects observed were measured and correlated with delayed enhancement magnetic resonance imaging and postmortem staining. No myocardial contrast was produced with any imaging setting when using C3C4 droplets or C3 droplets during low MI real-time imaging. However, myocardial contrast was observed in all 8 pigs with C3 droplets when using triggered high MI imaging and in 5 of 6 pigs that had 1.7 MHz real time-high MI imaging. Although quantitative myocardial contrast was lower with real-time high MI imaging than 1:1 triggering, the correlation between real-time resting defect size and infarct size was good (r=0.97; P<0.001), as was the correlation with number of transmural infarcted segments by delayed enhancement imaging. CONCLUSIONS: Targeted transthoracic acoustic activation of infused intravenous C3 nanodroplets is effective, resulting in echogenic and persistent microbubbles which provide real-time high MI visualization of perfusion defects.
Authors: Nikita Reznik; Guillaume Lajoinie; Oleksandr Shpak; Erik C Gelderblom; Ross Williams; Nico de Jong; Michel Versluis; Peter N Burns Journal: Ultrasound Med Biol Date: 2014-01-22 Impact factor: 2.998
Authors: Feng Xie; Shunji Gao; Juefei Wu; John Lof; Stanley Radio; Francois Vignon; William Shi; Jeffry Powers; Evan Unger; E Carr Everbach; Jinjin Liu; Thomas R Porter Journal: PLoS One Date: 2013-07-29 Impact factor: 3.240
Authors: Terry O Matsunaga; Paul S Sheeran; Samantha Luois; Jason E Streeter; Lee B Mullin; Bhaskar Banerjee; Paul A Dayton Journal: Theranostics Date: 2012-12-23 Impact factor: 11.556
Authors: Shih-Ying Wu; Samantha M Fix; Christopher B Arena; Cherry C Chen; Wenlan Zheng; Oluyemi O Olumolade; Virginie Papadopoulou; Anthony Novell; Paul A Dayton; Elisa E Konofagou Journal: Phys Med Biol Date: 2018-01-22 Impact factor: 3.609
Authors: Ping Zeng; Cheng Chen; John Lof; Elizabeth Stolze; Shouqiang Li; Xucai Chen; John Pacella; Flordeliza S Villanueva; Terry Matsunaga; E Carr Everbach; Hongwen Fei; Feng Xie; Thomas Porter Journal: Ultrasound Med Biol Date: 2022-08-30 Impact factor: 3.694
Authors: Michael Cimorelli; Michael A Flynn; Brett Angel; Emily Reimold; Sahil S Banka; Benjamin Andrien; Aaron Fafarman; Richard Huneke; Andrew Kohut; Steven Wrenn Journal: J Cardiovasc Transl Res Date: 2022-01-31 Impact factor: 3.216
Authors: Joseph P Marshalek; Paul S Sheeran; Pier Ingram; Paul A Dayton; Russell S Witte; Terry O Matsunaga Journal: J Control Release Date: 2016-09-26 Impact factor: 9.776
Authors: Ping Zeng; Lijun Qian; John Lof; Elizabeth Stolze; Soufiane El Kadi; Thomas Bargar; Jiri Sklenar; Terry Matsunaga; Feng Xie; Thomas R Porter Journal: J Am Soc Echocardiogr Date: 2021-03-09 Impact factor: 7.722
Authors: Songita A Choudhury; Feng Xie; Shelby Kutty; John Lof; Elizabeth Stolze; Thomas R Porter Journal: PLoS One Date: 2018-12-14 Impact factor: 3.240