A multi-pulse ultrasound technique for imaging of thick-shelled microbubbles demonstrated in vitro and in vivo.

Contrast enhanced ultrasound is a powerful diagnostic tool and ultrasound contrast media are based on microbubbles (MBs). The use of MBs in drug delivery applications and molecular imaging is a relatively new field of research which has gained significant interest during the last decade. MBs availab...

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Main Authors: Sigrid Berg, Siv Eggen, Kenneth Caidahl, Lars Dähne, Rune Hansen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2022-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0276292
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author Sigrid Berg
Siv Eggen
Kenneth Caidahl
Lars Dähne
Rune Hansen
author_facet Sigrid Berg
Siv Eggen
Kenneth Caidahl
Lars Dähne
Rune Hansen
author_sort Sigrid Berg
collection DOAJ
description Contrast enhanced ultrasound is a powerful diagnostic tool and ultrasound contrast media are based on microbubbles (MBs). The use of MBs in drug delivery applications and molecular imaging is a relatively new field of research which has gained significant interest during the last decade. MBs available for clinical use are fragile with short circulation half-lives due to the use of a thin encapsulating shell for stabilization of the gas core. Thick-shelled MBs can have improved circulation half-lives, incorporate larger amounts of drugs for enhanced drug delivery or facilitate targeting for use in molecular ultrasound imaging. However, methods for robust imaging of thick-shelled MBs are currently not available. We propose a simple multi-pulse imaging technique which is able to visualize thick-shelled polymeric MBs with a superior contrast-to-tissue ratio (CTR) compared to commercially available harmonic techniques. The method is implemented on a high-end ultrasound scanner and in-vitro imaging in a tissue mimicking flow phantom results in a CTR of up to 23 dB. A proof-of-concept study of molecular ultrasound imaging in a soft tissue inflammation model in rabbit is then presented where the new imaging technique showed an enhanced accumulation of targeted MBs in the inflamed tissue region compared to non-targeted MBs and a mean CTR of 13.3 dB for stationary MBs. The presence of fluorescently labelled MBs was verified by confocal microscopy imaging of tissue sections post-mortem.
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spelling doaj.art-fa2ce797d1974952a0d706695126f4952022-12-22T03:36:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-011711e027629210.1371/journal.pone.0276292A multi-pulse ultrasound technique for imaging of thick-shelled microbubbles demonstrated in vitro and in vivo.Sigrid BergSiv EggenKenneth CaidahlLars DähneRune HansenContrast enhanced ultrasound is a powerful diagnostic tool and ultrasound contrast media are based on microbubbles (MBs). The use of MBs in drug delivery applications and molecular imaging is a relatively new field of research which has gained significant interest during the last decade. MBs available for clinical use are fragile with short circulation half-lives due to the use of a thin encapsulating shell for stabilization of the gas core. Thick-shelled MBs can have improved circulation half-lives, incorporate larger amounts of drugs for enhanced drug delivery or facilitate targeting for use in molecular ultrasound imaging. However, methods for robust imaging of thick-shelled MBs are currently not available. We propose a simple multi-pulse imaging technique which is able to visualize thick-shelled polymeric MBs with a superior contrast-to-tissue ratio (CTR) compared to commercially available harmonic techniques. The method is implemented on a high-end ultrasound scanner and in-vitro imaging in a tissue mimicking flow phantom results in a CTR of up to 23 dB. A proof-of-concept study of molecular ultrasound imaging in a soft tissue inflammation model in rabbit is then presented where the new imaging technique showed an enhanced accumulation of targeted MBs in the inflamed tissue region compared to non-targeted MBs and a mean CTR of 13.3 dB for stationary MBs. The presence of fluorescently labelled MBs was verified by confocal microscopy imaging of tissue sections post-mortem.https://doi.org/10.1371/journal.pone.0276292
spellingShingle Sigrid Berg
Siv Eggen
Kenneth Caidahl
Lars Dähne
Rune Hansen
A multi-pulse ultrasound technique for imaging of thick-shelled microbubbles demonstrated in vitro and in vivo.
PLoS ONE
title A multi-pulse ultrasound technique for imaging of thick-shelled microbubbles demonstrated in vitro and in vivo.
title_full A multi-pulse ultrasound technique for imaging of thick-shelled microbubbles demonstrated in vitro and in vivo.
title_fullStr A multi-pulse ultrasound technique for imaging of thick-shelled microbubbles demonstrated in vitro and in vivo.
title_full_unstemmed A multi-pulse ultrasound technique for imaging of thick-shelled microbubbles demonstrated in vitro and in vivo.
title_short A multi-pulse ultrasound technique for imaging of thick-shelled microbubbles demonstrated in vitro and in vivo.
title_sort multi pulse ultrasound technique for imaging of thick shelled microbubbles demonstrated in vitro and in vivo
url https://doi.org/10.1371/journal.pone.0276292
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