Theoretical and Experimental Gas Volume Quantification of Micro- and Nanobubble Ultrasound Contrast Agents
The amount of gas in ultrasound contrast agents is related to their acoustic activity. Because of this relationship, gas volume has been used as a key variable in normalizing the in vitro and in vivo acoustic behavior of lipid shell-stabilized bubbles with different sizes and shell components. Despi...
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| Format: | Article |
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MDPI AG
2020-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/3/208 |
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| author | Eric C. Abenojar Ilya Bederman Al C. de Leon Jinle Zhu Judith Hadley Michael C. Kolios Agata A. Exner |
| author_facet | Eric C. Abenojar Ilya Bederman Al C. de Leon Jinle Zhu Judith Hadley Michael C. Kolios Agata A. Exner |
| author_sort | Eric C. Abenojar |
| collection | DOAJ |
| description | The amount of gas in ultrasound contrast agents is related to their acoustic activity. Because of this relationship, gas volume has been used as a key variable in normalizing the in vitro and in vivo acoustic behavior of lipid shell-stabilized bubbles with different sizes and shell components. Despite its importance, bubble gas volume has typically only been theoretically calculated based on bubble size and concentration that is typically measured using the Coulter counter for microbubbles and nanoparticle tracking analysis (NTA) for nanoscale bubbles. However, while these methods have been validated for the analysis of liquid or solid particles, their application in bubble analysis has not been rigorously studied. We have previously shown that resonant mass measurement (RMM) may be a better-suited technique for sub-micron bubble analysis, as it can measure both buoyant and non-buoyant particle size and concentration. Here, we provide validation of RMM bubble analysis by using headspace gas chromatography/mass spectrometry (GC/MS) to experimentally measure the gas volume of the bubble samples. This measurement was then used as ground truth to test the accuracy of theoretical gas volume predictions based on RMM, NTA (for nanobubbles), and Coulter counter (for microbubbles) measurements. The results show that the headspace GC/MS gas volume measurements agreed well with the theoretical predictions for the RMM of nanobubbles but not NTA. For nanobubbles , the theoretical gas volume using RMM was 10% lower than the experimental GC/MS measurements; meanwhile, using NTA resulted in an 82% lower predicted gas volume. For microbubbles, the experimental gas volume from the GC/MS measurements was 27% lower compared to RMM and 72% less compared to the Coulter counter results. This study demonstrates that the gas volume of nanobubbles and microbubbles can be reliably measured using headspace GC/MS to validate bubble size measurement techniques. We also conclude that the accuracy of theoretical predictions is highly dependent on proper size and concentration measurements. |
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| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-14T02:22:06Z |
| publishDate | 2020-03-01 |
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| series | Pharmaceutics |
| spelling | doaj.art-85b00c7ea7fd4cd4b98e01b0869d354a2022-12-22T02:18:00ZengMDPI AGPharmaceutics1999-49232020-03-0112320810.3390/pharmaceutics12030208pharmaceutics12030208Theoretical and Experimental Gas Volume Quantification of Micro- and Nanobubble Ultrasound Contrast AgentsEric C. Abenojar0Ilya Bederman1Al C. de Leon2Jinle Zhu3Judith Hadley4Michael C. Kolios5Agata A. Exner6Department of Radiology, Case Western Reserve University, 10900 Euclid Ave. Cleveland, OH 44106, USADepartment of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, 10900 Euclid Ave. Cleveland, OH 44106, USADepartment of Radiology, Case Western Reserve University, 10900 Euclid Ave. Cleveland, OH 44106, USADepartment of Radiology, Case Western Reserve University, 10900 Euclid Ave. Cleveland, OH 44106, USAMalvern Panalytical, Westborough, MA 01581, USADepartment of Physics, Ryerson University, Toronto, ON M5B 2K3, CanadaDepartment of Radiology, Case Western Reserve University, 10900 Euclid Ave. Cleveland, OH 44106, USAThe amount of gas in ultrasound contrast agents is related to their acoustic activity. Because of this relationship, gas volume has been used as a key variable in normalizing the in vitro and in vivo acoustic behavior of lipid shell-stabilized bubbles with different sizes and shell components. Despite its importance, bubble gas volume has typically only been theoretically calculated based on bubble size and concentration that is typically measured using the Coulter counter for microbubbles and nanoparticle tracking analysis (NTA) for nanoscale bubbles. However, while these methods have been validated for the analysis of liquid or solid particles, their application in bubble analysis has not been rigorously studied. We have previously shown that resonant mass measurement (RMM) may be a better-suited technique for sub-micron bubble analysis, as it can measure both buoyant and non-buoyant particle size and concentration. Here, we provide validation of RMM bubble analysis by using headspace gas chromatography/mass spectrometry (GC/MS) to experimentally measure the gas volume of the bubble samples. This measurement was then used as ground truth to test the accuracy of theoretical gas volume predictions based on RMM, NTA (for nanobubbles), and Coulter counter (for microbubbles) measurements. The results show that the headspace GC/MS gas volume measurements agreed well with the theoretical predictions for the RMM of nanobubbles but not NTA. For nanobubbles , the theoretical gas volume using RMM was 10% lower than the experimental GC/MS measurements; meanwhile, using NTA resulted in an 82% lower predicted gas volume. For microbubbles, the experimental gas volume from the GC/MS measurements was 27% lower compared to RMM and 72% less compared to the Coulter counter results. This study demonstrates that the gas volume of nanobubbles and microbubbles can be reliably measured using headspace GC/MS to validate bubble size measurement techniques. We also conclude that the accuracy of theoretical predictions is highly dependent on proper size and concentration measurements.https://www.mdpi.com/1999-4923/12/3/208gas chromatography/mass spectrometrycontrast agentsultrasoundnanobubblemicrobubbleresonant mass measurementdynamic light scatteringnanoparticle tracking analysiscoulter counterperfluoropropanegas volume |
| spellingShingle | Eric C. Abenojar Ilya Bederman Al C. de Leon Jinle Zhu Judith Hadley Michael C. Kolios Agata A. Exner Theoretical and Experimental Gas Volume Quantification of Micro- and Nanobubble Ultrasound Contrast Agents Pharmaceutics gas chromatography/mass spectrometry contrast agents ultrasound nanobubble microbubble resonant mass measurement dynamic light scattering nanoparticle tracking analysis coulter counter perfluoropropane gas volume |
| title | Theoretical and Experimental Gas Volume Quantification of Micro- and Nanobubble Ultrasound Contrast Agents |
| title_full | Theoretical and Experimental Gas Volume Quantification of Micro- and Nanobubble Ultrasound Contrast Agents |
| title_fullStr | Theoretical and Experimental Gas Volume Quantification of Micro- and Nanobubble Ultrasound Contrast Agents |
| title_full_unstemmed | Theoretical and Experimental Gas Volume Quantification of Micro- and Nanobubble Ultrasound Contrast Agents |
| title_short | Theoretical and Experimental Gas Volume Quantification of Micro- and Nanobubble Ultrasound Contrast Agents |
| title_sort | theoretical and experimental gas volume quantification of micro and nanobubble ultrasound contrast agents |
| topic | gas chromatography/mass spectrometry contrast agents ultrasound nanobubble microbubble resonant mass measurement dynamic light scattering nanoparticle tracking analysis coulter counter perfluoropropane gas volume |
| url | https://www.mdpi.com/1999-4923/12/3/208 |
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