Monodisperse versus Polydisperse Ultrasound Contrast Agents: In Vivo Sensitivity and safety in Rat and Pig
| Autor: | Tim Segers, Catherine Botteron, Alexandre Helbert, Victor Jeannot, Emmanuel Gaud, Peter Frinking |
|---|---|
| Přispěvatelé: | Physics of Fluids |
| Rok vydání: | 2020 |
| Předmět: |
Materials science
SonoVue Acoustics and Ultrasonics Swine Bubble Dispersity Biophysics Contrast Media 02 engineering and technology Lumason Monodisperse microbubbles 030218 nuclear medicine & medical imaging Rats Sprague-Dawley 03 medical and health sciences Sensitivity 0302 clinical medicine Flow focusing In vivo Animals Radiology Nuclear Medicine and imaging Ultrasonography Microbubbles Optison Radiological and Ultrasound Technology business.industry Ultrasound 22/2 OA procedure Ultrasound contrast agents 021001 nanoscience & nanotechnology Rats Luminity Definity Molecular imaging 0210 nano-technology business Sensitivity (electronics) Biomedical engineering |
| Zdroj: | Ultrasound in medicine and biology, 46(12), 3339-3352. Elsevier |
| ISSN: | 0301-5629 |
| DOI: | 10.1016/j.ultrasmedbio.2020.07.031 |
| Popis: | Recent advances in the field of monodisperse microbubble synthesis by flow focusing allow for the production of foam-free, highly concentrated and monodisperse lipid-coated microbubble suspensions. It has been found that in vitro, such monodisperse ultrasound contrast agents (UCAs) improve the sensitivity of contrast-enhanced ultrasound imaging. Here, we present the first in vivo study in the left ventricle of rat and pig with this new monodisperse bubble agent. We systematically characterize the acoustic sensitivity and safety of the agent at an imaging frequency of 2.5 MHz as compared with three commercial polydisperse UCAs (SonoVue/Lumason, Definity/Luminity and Optison) and one research-grade polydisperse agent with the same shell composition as the monodisperse bubbles. The monodisperse microbubbles, which had a diameter of 4.2 μm, crossed the pulmonary vasculature, and their echo signal could be measured at least as long as that of the polydisperse UCAs, indicating that microfluidically formed monodisperse microbubbles are stable in vivo. Furthermore, it was found that the sensitivity of the monodisperse agent, expressed as the mean echo power per injected bubble, was at least 10 times higher than that of the polydisperse UCAs. Finally, the safety profile of the monodisperse microbubble suspension was evaluated by injecting 400 and 2000 times the imaging dose, and neither physiologic nor pathologic changes were found, which is a first indication that monodisperse lipid-coated microbubbles formed by flow focusing are safe for in vivo use. The more uniform acoustic response and corresponding increased imaging sensitivity of the monodisperse agent may boost emerging applications of microbubbles and ultrasound such as molecular imaging and therapy. |
| Databáze: | OpenAIRE |
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