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...
Main Authors: | , , , , |
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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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. |
first_indexed | 2024-04-12T10:38:47Z |
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id | doaj.art-fa2ce797d1974952a0d706695126f495 |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-04-12T10:38:47Z |
publishDate | 2022-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
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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