Acoustic Behavior of a Reactivated, Commercially Available Ultrasound Contrast Agent

Songita A. Choudhury, Feng Xie, Paul A. Dayton, Thomas R. Porter

Research output: Research - peer-reviewArticle

  • 1 Citations

Abstract

Background Commercially available microbubbles such as Definity contain octafluoropropane encapsulated in a lipid shell. This perfluorocarbon can be compressed into liquid nanodroplets at room temperatures and activated with transthoracic diagnostic ultrasound. The aim of this study was to determine the size range and acoustic characteristics of Definity nanodroplets (DNDs) compared with Definity microbubbles (DMBs). Methods An in vitro flow system was used with a diagnostic ultrasound transducer (S5-1, iE33). DMBs were prepared using package insert instructions. DNDs were prepared by cooling DMBs in a −10°C to −15°C isopropyl alcohol bath before hand-pressurizing the solution. The formed DNDs were sized, diluted to 1% solutions, and infused continuously into a phosphate-buffered saline solution running within Silastic tubing. Acoustic intensity (AI) was compared with equivalent dilutions of DMBs at different mechanical indices (MIs) ranging from 0.2 to 1.4 (n = 6 comparisons at each MI) using real-time 56-Hz and triggered 2-Hz frame rates (FRs). A 3-cm-thick tissue-mimicking phantom was used to simulate transthoracic attenuation. In vivo transthoracic studies were performed in four normal pigs infused with 10% intravenous infusions of DMBs or DNDs at real-time and triggered end-systolic FRs to compare differences in myocardial and left ventricular cavity AI. Results DNDs were smaller than DMBs and ranged in size from 50 to 1,000 nm. In vitro studies revealed that at an MI of 0.2 and an FR of 56 Hz, DMBs had high AI (37 ± 2 dB), but AI dropped to 25 ± 2 dB at an MI of 1.0 (P < .001, analysis of variance). In comparison, DNDs had virtually no AI at MIs of 0.2 to 0.6 at both triggered and 56-Hz FRs (1 ± 0 dB), but AI increased to 34 ± 2 dB at an MI of 1.4 using an FR of 56 Hz (P < .001 vs MI of 0.2). AI also persisted longer at 56 Hz with DNDs when using higher MIs. In vivo studies demonstrated higher myocardial AI for DNDs at higher MIs when using real-time FR, most likely from microvascular nanodroplet activation. Conclusion These data indicate significant differences in acoustic responses of the commercially available DMBs when administered as an equivalent number of DNDs. The DND formulation may render them more useful for high-MI real-time imaging and other targeted transthoracic diagnostic applications.

LanguageEnglish (US)
Pages189-197
Number of pages9
JournalJournal of the American Society of Echocardiography
Volume30
Issue number2
DOIs
StatePublished - Feb 1 2017

Fingerprint

Acoustics
Contrast Media
Definity
Microbubbles
Ultrasonography
In Vitro Techniques
perflutren
Product Labeling
Fluorocarbons
2-Propanol
Transducers
Baths
Intravenous Infusions
Sodium Chloride
Running
Analysis of Variance
Swine
Hand
Phosphates
Lipids

Keywords

  • Acoustic activation
  • Droplets
  • Microbubbles

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

Acoustic Behavior of a Reactivated, Commercially Available Ultrasound Contrast Agent. / Choudhury, Songita A.; Xie, Feng; Dayton, Paul A.; Porter, Thomas R.

In: Journal of the American Society of Echocardiography, Vol. 30, No. 2, 01.02.2017, p. 189-197.

Research output: Research - peer-reviewArticle

@article{2d6bb0ad26aa45d3af0123cc01105d23,
title = "Acoustic Behavior of a Reactivated, Commercially Available Ultrasound Contrast Agent",
abstract = "Background Commercially available microbubbles such as Definity contain octafluoropropane encapsulated in a lipid shell. This perfluorocarbon can be compressed into liquid nanodroplets at room temperatures and activated with transthoracic diagnostic ultrasound. The aim of this study was to determine the size range and acoustic characteristics of Definity nanodroplets (DNDs) compared with Definity microbubbles (DMBs). Methods An in vitro flow system was used with a diagnostic ultrasound transducer (S5-1, iE33). DMBs were prepared using package insert instructions. DNDs were prepared by cooling DMBs in a −10°C to −15°C isopropyl alcohol bath before hand-pressurizing the solution. The formed DNDs were sized, diluted to 1% solutions, and infused continuously into a phosphate-buffered saline solution running within Silastic tubing. Acoustic intensity (AI) was compared with equivalent dilutions of DMBs at different mechanical indices (MIs) ranging from 0.2 to 1.4 (n = 6 comparisons at each MI) using real-time 56-Hz and triggered 2-Hz frame rates (FRs). A 3-cm-thick tissue-mimicking phantom was used to simulate transthoracic attenuation. In vivo transthoracic studies were performed in four normal pigs infused with 10% intravenous infusions of DMBs or DNDs at real-time and triggered end-systolic FRs to compare differences in myocardial and left ventricular cavity AI. Results DNDs were smaller than DMBs and ranged in size from 50 to 1,000 nm. In vitro studies revealed that at an MI of 0.2 and an FR of 56 Hz, DMBs had high AI (37 ± 2 dB), but AI dropped to 25 ± 2 dB at an MI of 1.0 (P < .001, analysis of variance). In comparison, DNDs had virtually no AI at MIs of 0.2 to 0.6 at both triggered and 56-Hz FRs (1 ± 0 dB), but AI increased to 34 ± 2 dB at an MI of 1.4 using an FR of 56 Hz (P < .001 vs MI of 0.2). AI also persisted longer at 56 Hz with DNDs when using higher MIs. In vivo studies demonstrated higher myocardial AI for DNDs at higher MIs when using real-time FR, most likely from microvascular nanodroplet activation. Conclusion These data indicate significant differences in acoustic responses of the commercially available DMBs when administered as an equivalent number of DNDs. The DND formulation may render them more useful for high-MI real-time imaging and other targeted transthoracic diagnostic applications.",
keywords = "Acoustic activation, Droplets, Microbubbles",
author = "Choudhury, {Songita A.} and Feng Xie and Dayton, {Paul A.} and Porter, {Thomas R.}",
year = "2017",
month = "2",
doi = "10.1016/j.echo.2016.10.015",
volume = "30",
pages = "189--197",
journal = "Journal of the American Society of Echocardiography",
issn = "0894-7317",
publisher = "Mosby Inc.",
number = "2",

}

TY - JOUR

T1 - Acoustic Behavior of a Reactivated, Commercially Available Ultrasound Contrast Agent

AU - Choudhury,Songita A.

AU - Xie,Feng

AU - Dayton,Paul A.

AU - Porter,Thomas R.

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Background Commercially available microbubbles such as Definity contain octafluoropropane encapsulated in a lipid shell. This perfluorocarbon can be compressed into liquid nanodroplets at room temperatures and activated with transthoracic diagnostic ultrasound. The aim of this study was to determine the size range and acoustic characteristics of Definity nanodroplets (DNDs) compared with Definity microbubbles (DMBs). Methods An in vitro flow system was used with a diagnostic ultrasound transducer (S5-1, iE33). DMBs were prepared using package insert instructions. DNDs were prepared by cooling DMBs in a −10°C to −15°C isopropyl alcohol bath before hand-pressurizing the solution. The formed DNDs were sized, diluted to 1% solutions, and infused continuously into a phosphate-buffered saline solution running within Silastic tubing. Acoustic intensity (AI) was compared with equivalent dilutions of DMBs at different mechanical indices (MIs) ranging from 0.2 to 1.4 (n = 6 comparisons at each MI) using real-time 56-Hz and triggered 2-Hz frame rates (FRs). A 3-cm-thick tissue-mimicking phantom was used to simulate transthoracic attenuation. In vivo transthoracic studies were performed in four normal pigs infused with 10% intravenous infusions of DMBs or DNDs at real-time and triggered end-systolic FRs to compare differences in myocardial and left ventricular cavity AI. Results DNDs were smaller than DMBs and ranged in size from 50 to 1,000 nm. In vitro studies revealed that at an MI of 0.2 and an FR of 56 Hz, DMBs had high AI (37 ± 2 dB), but AI dropped to 25 ± 2 dB at an MI of 1.0 (P < .001, analysis of variance). In comparison, DNDs had virtually no AI at MIs of 0.2 to 0.6 at both triggered and 56-Hz FRs (1 ± 0 dB), but AI increased to 34 ± 2 dB at an MI of 1.4 using an FR of 56 Hz (P < .001 vs MI of 0.2). AI also persisted longer at 56 Hz with DNDs when using higher MIs. In vivo studies demonstrated higher myocardial AI for DNDs at higher MIs when using real-time FR, most likely from microvascular nanodroplet activation. Conclusion These data indicate significant differences in acoustic responses of the commercially available DMBs when administered as an equivalent number of DNDs. The DND formulation may render them more useful for high-MI real-time imaging and other targeted transthoracic diagnostic applications.

AB - Background Commercially available microbubbles such as Definity contain octafluoropropane encapsulated in a lipid shell. This perfluorocarbon can be compressed into liquid nanodroplets at room temperatures and activated with transthoracic diagnostic ultrasound. The aim of this study was to determine the size range and acoustic characteristics of Definity nanodroplets (DNDs) compared with Definity microbubbles (DMBs). Methods An in vitro flow system was used with a diagnostic ultrasound transducer (S5-1, iE33). DMBs were prepared using package insert instructions. DNDs were prepared by cooling DMBs in a −10°C to −15°C isopropyl alcohol bath before hand-pressurizing the solution. The formed DNDs were sized, diluted to 1% solutions, and infused continuously into a phosphate-buffered saline solution running within Silastic tubing. Acoustic intensity (AI) was compared with equivalent dilutions of DMBs at different mechanical indices (MIs) ranging from 0.2 to 1.4 (n = 6 comparisons at each MI) using real-time 56-Hz and triggered 2-Hz frame rates (FRs). A 3-cm-thick tissue-mimicking phantom was used to simulate transthoracic attenuation. In vivo transthoracic studies were performed in four normal pigs infused with 10% intravenous infusions of DMBs or DNDs at real-time and triggered end-systolic FRs to compare differences in myocardial and left ventricular cavity AI. Results DNDs were smaller than DMBs and ranged in size from 50 to 1,000 nm. In vitro studies revealed that at an MI of 0.2 and an FR of 56 Hz, DMBs had high AI (37 ± 2 dB), but AI dropped to 25 ± 2 dB at an MI of 1.0 (P < .001, analysis of variance). In comparison, DNDs had virtually no AI at MIs of 0.2 to 0.6 at both triggered and 56-Hz FRs (1 ± 0 dB), but AI increased to 34 ± 2 dB at an MI of 1.4 using an FR of 56 Hz (P < .001 vs MI of 0.2). AI also persisted longer at 56 Hz with DNDs when using higher MIs. In vivo studies demonstrated higher myocardial AI for DNDs at higher MIs when using real-time FR, most likely from microvascular nanodroplet activation. Conclusion These data indicate significant differences in acoustic responses of the commercially available DMBs when administered as an equivalent number of DNDs. The DND formulation may render them more useful for high-MI real-time imaging and other targeted transthoracic diagnostic applications.

KW - Acoustic activation

KW - Droplets

KW - Microbubbles

UR - http://www.scopus.com/inward/record.url?scp=85007601794&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85007601794&partnerID=8YFLogxK

U2 - 10.1016/j.echo.2016.10.015

DO - 10.1016/j.echo.2016.10.015

M3 - Article

VL - 30

SP - 189

EP - 197

JO - Journal of the American Society of Echocardiography

T2 - Journal of the American Society of Echocardiography

JF - Journal of the American Society of Echocardiography

SN - 0894-7317

IS - 2

ER -