Ultrasound contrast agents: Basic principles

Fabrizio Calliada, Rodolfo Campani, Olivia Bottinelli, Anna Bozzini, Maria Grazia Sommaruga

Research output: Contribution to journalArticle

226 Citations (Scopus)

Abstract

Introduction. Ultrasonography lacked substances to be administered to patients to improve or increase the diagnostic yield, which is peculiar considering that contrast agents have long been used with all the other imaging techniques. Fortunately some contrast agents, most of them consisting in gas microbubbles, have been recently introduced for ultrasound imaging too: this review will focus on their history, behavior, current applications and future developments. Echocontrast agent research is in progress and many new agents are expected to be marketed this and next year, to be added to Leovist(TM) by Schering AG (Berlin, Germany), to enhance the ultrasound signal safely and effectively. No definitive conclusions can be drawn yet on the actual merits of each contrast agent, but all of them seem to be both effective and safe, meaning that their future success will depend on the relative cost-effectiveness and peculiarities. The basic principles of echocontrast agents. The microbubbles act as echo-enhancers by basically the same mechanism as that determining echo-scattering in all the other cases of diagnostic ultrasound, namely that the backscattering echo intensity is proportional to the change in acoustic impedance between the blood and the gas making the bubbles. The different acoustic impedance at this interface is very high and in fact all of the incident sound is reflected, even though not all of it will of course go back to the transducer. But the acoustic wave reflection, though nearly complete, would not be sufficient to determine a strong US enhancement because the microbubbles are very small and are sparse in the circulation. Moreover, reflectivity is proportional to the fourth power of a particle diameter but also directly proportional to the concentration of the particles themselves. Second harmonic imaging. As we said above, the microbubbles reached by an ultrasound signal resonate with a specific frequency depeding on microbubble diameter. However, the main resonance frequency is not the only resonance frequency of the bubble itself and multiple frequencies of the fundamental one are emitted, just like in a musical instrument. These harmonic frequencies have decreasing intensity, but the second frequency, known as the second harmonic, is still strong enough to be used for diagnostic purposes. The theoretical advantage of the harmonic over the fundamental frequency is that only contrast agent microbubbles resonate with harmonic frequencies, while adjacent tissues do not resonate, or else their harmonic resonation is very little. Thus, using a unit especially set to produce ultrasounds at a given frequency (3.5 MHz) and receive an ultrasound signal twice as powerful (7 MHz) it will be possible to show the contrast agent only, without any artifact from the surrounding anatomical structures, with a markedly improved signal-to-noise ratio. A similar effect to digital subtraction in angiography can thus be obtained, even though through a totally different process. Moreover, second harmonic imaging permits to show extremely small vessels (down to 40 μm) with very slow flow, which would be missed with a conventional method. B-mode imaging can also depict the microbubbles in the myocardium suppressing nearly all the artifacts from cardiac muscle motion. Recently a peculiar behavior of microbubbles has been observed which may permit contrast agent detection even in capillaries. This method is variously known as sonoscintigraphy, loss of correlation, stimulated acoustic emission and transient scattering. The contrast agent microbubbles reached by an ultrasound beam powerful enough explode producing a strong and very short backscatter echo which is read by the unit as a Doppler signal and results in a color pixel where the individual microbubble exploded. Conclusions. The microbubble contrast agents developed and introduced as safe and effective echo-enhancers in present-day clinical practice will open up new oppurtunities and result in an amazing revolution of ultrasonography as we know it now.

Original languageEnglish
JournalEuropean Journal of Radiology
Volume27
Issue numberSUPPL. 2
DOIs
Publication statusPublished - May 1998

Fingerprint

Microbubbles
Contrast Media
Ultrasonography
Acoustics
Electric Impedance
Artifacts
Myocardium
Gases
Digital Subtraction Angiography
Signal-To-Noise Ratio
Berlin
Transducers
Cost-Benefit Analysis
Germany
Color
History

Keywords

  • Hand-made agents
  • Microbubbles
  • Ultrasound

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Ultrasound contrast agents : Basic principles. / Calliada, Fabrizio; Campani, Rodolfo; Bottinelli, Olivia; Bozzini, Anna; Sommaruga, Maria Grazia.

In: European Journal of Radiology, Vol. 27, No. SUPPL. 2, 05.1998.

Research output: Contribution to journalArticle

@article{760cfdac622348698550fc47e6a65554,
title = "Ultrasound contrast agents: Basic principles",
abstract = "Introduction. Ultrasonography lacked substances to be administered to patients to improve or increase the diagnostic yield, which is peculiar considering that contrast agents have long been used with all the other imaging techniques. Fortunately some contrast agents, most of them consisting in gas microbubbles, have been recently introduced for ultrasound imaging too: this review will focus on their history, behavior, current applications and future developments. Echocontrast agent research is in progress and many new agents are expected to be marketed this and next year, to be added to Leovist(TM) by Schering AG (Berlin, Germany), to enhance the ultrasound signal safely and effectively. No definitive conclusions can be drawn yet on the actual merits of each contrast agent, but all of them seem to be both effective and safe, meaning that their future success will depend on the relative cost-effectiveness and peculiarities. The basic principles of echocontrast agents. The microbubbles act as echo-enhancers by basically the same mechanism as that determining echo-scattering in all the other cases of diagnostic ultrasound, namely that the backscattering echo intensity is proportional to the change in acoustic impedance between the blood and the gas making the bubbles. The different acoustic impedance at this interface is very high and in fact all of the incident sound is reflected, even though not all of it will of course go back to the transducer. But the acoustic wave reflection, though nearly complete, would not be sufficient to determine a strong US enhancement because the microbubbles are very small and are sparse in the circulation. Moreover, reflectivity is proportional to the fourth power of a particle diameter but also directly proportional to the concentration of the particles themselves. Second harmonic imaging. As we said above, the microbubbles reached by an ultrasound signal resonate with a specific frequency depeding on microbubble diameter. However, the main resonance frequency is not the only resonance frequency of the bubble itself and multiple frequencies of the fundamental one are emitted, just like in a musical instrument. These harmonic frequencies have decreasing intensity, but the second frequency, known as the second harmonic, is still strong enough to be used for diagnostic purposes. The theoretical advantage of the harmonic over the fundamental frequency is that only contrast agent microbubbles resonate with harmonic frequencies, while adjacent tissues do not resonate, or else their harmonic resonation is very little. Thus, using a unit especially set to produce ultrasounds at a given frequency (3.5 MHz) and receive an ultrasound signal twice as powerful (7 MHz) it will be possible to show the contrast agent only, without any artifact from the surrounding anatomical structures, with a markedly improved signal-to-noise ratio. A similar effect to digital subtraction in angiography can thus be obtained, even though through a totally different process. Moreover, second harmonic imaging permits to show extremely small vessels (down to 40 μm) with very slow flow, which would be missed with a conventional method. B-mode imaging can also depict the microbubbles in the myocardium suppressing nearly all the artifacts from cardiac muscle motion. Recently a peculiar behavior of microbubbles has been observed which may permit contrast agent detection even in capillaries. This method is variously known as sonoscintigraphy, loss of correlation, stimulated acoustic emission and transient scattering. The contrast agent microbubbles reached by an ultrasound beam powerful enough explode producing a strong and very short backscatter echo which is read by the unit as a Doppler signal and results in a color pixel where the individual microbubble exploded. Conclusions. The microbubble contrast agents developed and introduced as safe and effective echo-enhancers in present-day clinical practice will open up new oppurtunities and result in an amazing revolution of ultrasonography as we know it now.",
keywords = "Hand-made agents, Microbubbles, Ultrasound",
author = "Fabrizio Calliada and Rodolfo Campani and Olivia Bottinelli and Anna Bozzini and Sommaruga, {Maria Grazia}",
year = "1998",
month = "5",
doi = "10.1016/S0720-048X(98)00057-6",
language = "English",
volume = "27",
journal = "European Journal of Radiology",
issn = "0720-048X",
publisher = "Elsevier Ireland Ltd",
number = "SUPPL. 2",

}

TY - JOUR

T1 - Ultrasound contrast agents

T2 - Basic principles

AU - Calliada, Fabrizio

AU - Campani, Rodolfo

AU - Bottinelli, Olivia

AU - Bozzini, Anna

AU - Sommaruga, Maria Grazia

PY - 1998/5

Y1 - 1998/5

N2 - Introduction. Ultrasonography lacked substances to be administered to patients to improve or increase the diagnostic yield, which is peculiar considering that contrast agents have long been used with all the other imaging techniques. Fortunately some contrast agents, most of them consisting in gas microbubbles, have been recently introduced for ultrasound imaging too: this review will focus on their history, behavior, current applications and future developments. Echocontrast agent research is in progress and many new agents are expected to be marketed this and next year, to be added to Leovist(TM) by Schering AG (Berlin, Germany), to enhance the ultrasound signal safely and effectively. No definitive conclusions can be drawn yet on the actual merits of each contrast agent, but all of them seem to be both effective and safe, meaning that their future success will depend on the relative cost-effectiveness and peculiarities. The basic principles of echocontrast agents. The microbubbles act as echo-enhancers by basically the same mechanism as that determining echo-scattering in all the other cases of diagnostic ultrasound, namely that the backscattering echo intensity is proportional to the change in acoustic impedance between the blood and the gas making the bubbles. The different acoustic impedance at this interface is very high and in fact all of the incident sound is reflected, even though not all of it will of course go back to the transducer. But the acoustic wave reflection, though nearly complete, would not be sufficient to determine a strong US enhancement because the microbubbles are very small and are sparse in the circulation. Moreover, reflectivity is proportional to the fourth power of a particle diameter but also directly proportional to the concentration of the particles themselves. Second harmonic imaging. As we said above, the microbubbles reached by an ultrasound signal resonate with a specific frequency depeding on microbubble diameter. However, the main resonance frequency is not the only resonance frequency of the bubble itself and multiple frequencies of the fundamental one are emitted, just like in a musical instrument. These harmonic frequencies have decreasing intensity, but the second frequency, known as the second harmonic, is still strong enough to be used for diagnostic purposes. The theoretical advantage of the harmonic over the fundamental frequency is that only contrast agent microbubbles resonate with harmonic frequencies, while adjacent tissues do not resonate, or else their harmonic resonation is very little. Thus, using a unit especially set to produce ultrasounds at a given frequency (3.5 MHz) and receive an ultrasound signal twice as powerful (7 MHz) it will be possible to show the contrast agent only, without any artifact from the surrounding anatomical structures, with a markedly improved signal-to-noise ratio. A similar effect to digital subtraction in angiography can thus be obtained, even though through a totally different process. Moreover, second harmonic imaging permits to show extremely small vessels (down to 40 μm) with very slow flow, which would be missed with a conventional method. B-mode imaging can also depict the microbubbles in the myocardium suppressing nearly all the artifacts from cardiac muscle motion. Recently a peculiar behavior of microbubbles has been observed which may permit contrast agent detection even in capillaries. This method is variously known as sonoscintigraphy, loss of correlation, stimulated acoustic emission and transient scattering. The contrast agent microbubbles reached by an ultrasound beam powerful enough explode producing a strong and very short backscatter echo which is read by the unit as a Doppler signal and results in a color pixel where the individual microbubble exploded. Conclusions. The microbubble contrast agents developed and introduced as safe and effective echo-enhancers in present-day clinical practice will open up new oppurtunities and result in an amazing revolution of ultrasonography as we know it now.

AB - Introduction. Ultrasonography lacked substances to be administered to patients to improve or increase the diagnostic yield, which is peculiar considering that contrast agents have long been used with all the other imaging techniques. Fortunately some contrast agents, most of them consisting in gas microbubbles, have been recently introduced for ultrasound imaging too: this review will focus on their history, behavior, current applications and future developments. Echocontrast agent research is in progress and many new agents are expected to be marketed this and next year, to be added to Leovist(TM) by Schering AG (Berlin, Germany), to enhance the ultrasound signal safely and effectively. No definitive conclusions can be drawn yet on the actual merits of each contrast agent, but all of them seem to be both effective and safe, meaning that their future success will depend on the relative cost-effectiveness and peculiarities. The basic principles of echocontrast agents. The microbubbles act as echo-enhancers by basically the same mechanism as that determining echo-scattering in all the other cases of diagnostic ultrasound, namely that the backscattering echo intensity is proportional to the change in acoustic impedance between the blood and the gas making the bubbles. The different acoustic impedance at this interface is very high and in fact all of the incident sound is reflected, even though not all of it will of course go back to the transducer. But the acoustic wave reflection, though nearly complete, would not be sufficient to determine a strong US enhancement because the microbubbles are very small and are sparse in the circulation. Moreover, reflectivity is proportional to the fourth power of a particle diameter but also directly proportional to the concentration of the particles themselves. Second harmonic imaging. As we said above, the microbubbles reached by an ultrasound signal resonate with a specific frequency depeding on microbubble diameter. However, the main resonance frequency is not the only resonance frequency of the bubble itself and multiple frequencies of the fundamental one are emitted, just like in a musical instrument. These harmonic frequencies have decreasing intensity, but the second frequency, known as the second harmonic, is still strong enough to be used for diagnostic purposes. The theoretical advantage of the harmonic over the fundamental frequency is that only contrast agent microbubbles resonate with harmonic frequencies, while adjacent tissues do not resonate, or else their harmonic resonation is very little. Thus, using a unit especially set to produce ultrasounds at a given frequency (3.5 MHz) and receive an ultrasound signal twice as powerful (7 MHz) it will be possible to show the contrast agent only, without any artifact from the surrounding anatomical structures, with a markedly improved signal-to-noise ratio. A similar effect to digital subtraction in angiography can thus be obtained, even though through a totally different process. Moreover, second harmonic imaging permits to show extremely small vessels (down to 40 μm) with very slow flow, which would be missed with a conventional method. B-mode imaging can also depict the microbubbles in the myocardium suppressing nearly all the artifacts from cardiac muscle motion. Recently a peculiar behavior of microbubbles has been observed which may permit contrast agent detection even in capillaries. This method is variously known as sonoscintigraphy, loss of correlation, stimulated acoustic emission and transient scattering. The contrast agent microbubbles reached by an ultrasound beam powerful enough explode producing a strong and very short backscatter echo which is read by the unit as a Doppler signal and results in a color pixel where the individual microbubble exploded. Conclusions. The microbubble contrast agents developed and introduced as safe and effective echo-enhancers in present-day clinical practice will open up new oppurtunities and result in an amazing revolution of ultrasonography as we know it now.

KW - Hand-made agents

KW - Microbubbles

KW - Ultrasound

UR - http://www.scopus.com/inward/record.url?scp=0032078295&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032078295&partnerID=8YFLogxK

U2 - 10.1016/S0720-048X(98)00057-6

DO - 10.1016/S0720-048X(98)00057-6

M3 - Article

C2 - 9652516

AN - SCOPUS:0032078295

VL - 27

JO - European Journal of Radiology

JF - European Journal of Radiology

SN - 0720-048X

IS - SUPPL. 2

ER -