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Effect of perfluorocarbon composition on activation of phase‐changing ultrasound contrast agents
BACKGROUND: While microbubble contrast agents (MCAs) are commonly used in ultrasound (US), they are inherently limited to vascular targets due to their size. Alternatively, phase‐changing nanodroplet contrast agents (PNCAs) can be delivered as nanoscale agents (i.e., small enough to extravasate), bu...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9041204/ https://www.ncbi.nlm.nih.gov/pubmed/35195908 http://dx.doi.org/10.1002/mp.15564 |
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author | Mitcham, Trevor M. Nevozhay, Dmitry Chen, Yunyun Nguyen, Linh D. Pinton, Gianmarco F. Lai, Stephen Y. Sokolov, Konstantin V. Bouchard, Richard R. |
author_facet | Mitcham, Trevor M. Nevozhay, Dmitry Chen, Yunyun Nguyen, Linh D. Pinton, Gianmarco F. Lai, Stephen Y. Sokolov, Konstantin V. Bouchard, Richard R. |
author_sort | Mitcham, Trevor M. |
collection | PubMed |
description | BACKGROUND: While microbubble contrast agents (MCAs) are commonly used in ultrasound (US), they are inherently limited to vascular targets due to their size. Alternatively, phase‐changing nanodroplet contrast agents (PNCAs) can be delivered as nanoscale agents (i.e., small enough to extravasate), but when exposed to a US field of sufficient mechanical index (MI), they convert to MCAs, which can be visualized with high contrast using nonlinear US. PURPOSE: To investigate the effect of perfluorocarbon (PFC) core composition and presence of cholesterol in particle coatings on stability and image contrast generated from acoustic activation of PNCAs using high‐frequency US suitable for clinical imaging. METHODS: PNCAs with varied core compositions (i.e., mixtures of perfluoropentane [C5] and/or perfluorohexane [C6]) and two coating formulations (i.e., with and without cholesterol) were characterized and investigated for thermal/temporal stability and postactivation, nonlinear US contrast in phantom and in vivo environments. Through hydrophone measurements and nonlinear numerical modeling, MI was estimated for pulse sequences used for PNCA activation. RESULTS: All PNCA compositions were characterized to have similar diameters (249–267 nm) and polydispersity (0.151–0.185) following fabrication. While PNCAs with majority C5 core composition showed higher levels of spontaneous signal (i.e., not due to US activation) in phantoms than C6‐majority PNCAs, all compositions were stable during imaging experiments. When activating PNCAs with a 12.3‐MHz US pulse (MI = 1.1), C6‐core particles with cholesterol‐free coatings (i.e., CF‐C6‐100 particles) generated a median contrast of 3.1, which was significantly higher (p < 0.001) than other formulations. Further, CF‐C6‐100 particles were activated in a murine model, generating US contrast [Formula: see text] 3.4. CONCLUSION: C6‐core PNCAs can provide high‐contrast US imaging with minimal nonspecific activation in phantom and in vivo environments. |
format | Online Article Text |
id | pubmed-9041204 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90412042022-04-26 Effect of perfluorocarbon composition on activation of phase‐changing ultrasound contrast agents Mitcham, Trevor M. Nevozhay, Dmitry Chen, Yunyun Nguyen, Linh D. Pinton, Gianmarco F. Lai, Stephen Y. Sokolov, Konstantin V. Bouchard, Richard R. Med Phys DIAGNOSTIC IMAGING (IONIZING AND NON‐IONIZING) BACKGROUND: While microbubble contrast agents (MCAs) are commonly used in ultrasound (US), they are inherently limited to vascular targets due to their size. Alternatively, phase‐changing nanodroplet contrast agents (PNCAs) can be delivered as nanoscale agents (i.e., small enough to extravasate), but when exposed to a US field of sufficient mechanical index (MI), they convert to MCAs, which can be visualized with high contrast using nonlinear US. PURPOSE: To investigate the effect of perfluorocarbon (PFC) core composition and presence of cholesterol in particle coatings on stability and image contrast generated from acoustic activation of PNCAs using high‐frequency US suitable for clinical imaging. METHODS: PNCAs with varied core compositions (i.e., mixtures of perfluoropentane [C5] and/or perfluorohexane [C6]) and two coating formulations (i.e., with and without cholesterol) were characterized and investigated for thermal/temporal stability and postactivation, nonlinear US contrast in phantom and in vivo environments. Through hydrophone measurements and nonlinear numerical modeling, MI was estimated for pulse sequences used for PNCA activation. RESULTS: All PNCA compositions were characterized to have similar diameters (249–267 nm) and polydispersity (0.151–0.185) following fabrication. While PNCAs with majority C5 core composition showed higher levels of spontaneous signal (i.e., not due to US activation) in phantoms than C6‐majority PNCAs, all compositions were stable during imaging experiments. When activating PNCAs with a 12.3‐MHz US pulse (MI = 1.1), C6‐core particles with cholesterol‐free coatings (i.e., CF‐C6‐100 particles) generated a median contrast of 3.1, which was significantly higher (p < 0.001) than other formulations. Further, CF‐C6‐100 particles were activated in a murine model, generating US contrast [Formula: see text] 3.4. CONCLUSION: C6‐core PNCAs can provide high‐contrast US imaging with minimal nonspecific activation in phantom and in vivo environments. John Wiley and Sons Inc. 2022-03-07 2022-04 /pmc/articles/PMC9041204/ /pubmed/35195908 http://dx.doi.org/10.1002/mp.15564 Text en © 2022 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | DIAGNOSTIC IMAGING (IONIZING AND NON‐IONIZING) Mitcham, Trevor M. Nevozhay, Dmitry Chen, Yunyun Nguyen, Linh D. Pinton, Gianmarco F. Lai, Stephen Y. Sokolov, Konstantin V. Bouchard, Richard R. Effect of perfluorocarbon composition on activation of phase‐changing ultrasound contrast agents |
title | Effect of perfluorocarbon composition on activation of phase‐changing ultrasound contrast agents |
title_full | Effect of perfluorocarbon composition on activation of phase‐changing ultrasound contrast agents |
title_fullStr | Effect of perfluorocarbon composition on activation of phase‐changing ultrasound contrast agents |
title_full_unstemmed | Effect of perfluorocarbon composition on activation of phase‐changing ultrasound contrast agents |
title_short | Effect of perfluorocarbon composition on activation of phase‐changing ultrasound contrast agents |
title_sort | effect of perfluorocarbon composition on activation of phase‐changing ultrasound contrast agents |
topic | DIAGNOSTIC IMAGING (IONIZING AND NON‐IONIZING) |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9041204/ https://www.ncbi.nlm.nih.gov/pubmed/35195908 http://dx.doi.org/10.1002/mp.15564 |
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