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    Contrast enhanced ultrasound imaging by nature-inspired ultrastable echogenic nanobubbles

    Year: 2019

    Journal: Nanoscale, Volume 11, SEP 7, page 15647–15658

    Authors: de Leon, Al; Perera, Reshani; Hernandez, Christopher; Cooley, Michaela; Jung, Olive; Jeganathan, Selva; Abenojar, Eric; Fishbein, Grace; Sojahrood, Amin Jafari; Emerson, Corey C.; Stewart, Phoebe L.; Kolios, Michael C.; Exner, Agata A.

    Organizations: National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1R01EB025741-01]; Office of the Assistant Secretary of Defense for Health Affairs, through the Prostate Cancer Research Program [W81XWH-16-1-0372]; Case Comprehensive Cancer Center [P30CA043703, T32GM008803, T32GM007250-42]; NATIONAL CANCER INSTITUTEUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30CA043703] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF BIOMEDICAL IMAGING AND BIOENGINEERINGUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Biomedical Imaging & Bioengineering (NIBIB) [R01EB025741] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of General Medical Sciences (NIGMS) [T32GM008803] Funding Source: NIH RePORTER

    Advancement of ultrasound molecular imaging applications requires not only a reduction in size of the ultrasound contrast agents (UCAs) but also a significant improvement in the in vivo stability of the shell-stabilized gas bubble. The transition from first generation to second generation UCAs was marked by an advancement in stability as air was replaced by a hydrophobic gas, such as perfluoropropane and sulfur hexafluoride. Further improvement can be realized by focusing on how well the UCAs shell can retain the encapsulated gas under extreme mechanical deformations. Here we report the next generation of UCAs for which we engineered the shell structure to impart much better stability under repeated prolonged oscillation due to ultrasound, and large changes in shear and turbulence as it circulates within the body. By adapting an architecture with two layers of contrasting elastic properties similar to bacterial cell envelopes, our ultrastable nanobubbles (NBs) withstand continuous in vitro exposure to ultrasound with minimal signal decay and have a significant delay on the onset of in vivo signal decay in kidney, liver, and tumor. Development of ultrastable NBs can potentially expand the role of ultrasound in molecular imaging, theranostics, and drug delivery.
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