Abstract
Nanobubbles (NBs) are of high interest for ultrasound (US) imaging as contrast agents and therapy as cavitation nuclei. Because of their instability (Laplace pressure bubble catastrophe) and low sensitivity to US, reducing the size of commonly used microbubbles to submicron-size is not trivial. We introduce stabilized NBs in the 100–250-nm size range, manufactured by agitating human serum albumin and perfluoro-propane. These NBs were exposed to 3.34- and 5.39-MHz US, and their sensitivity to US was proven by detecting inertial cavitation. The cavitation-threshold information was used to run a numerical parametric study based on a modified Rayleigh-Plesset equation (with a Newtonian rheology model). The determined values of surface tension ranged from 0 N/m to 0.06 N/m. The corresponding values of dilatational viscosity ranged from 5.10−10 Ns/m to 1.10−9 Ns/m. These parameters were reported to be 0.6 N/m and 1.10−8 Ns/m for the reference microbubble contrast agent. This result suggests the possibility of using albumin as a stabilizer for the nanobubbles that could be maintained in circulation and presenting satisfying US sensitivity, even in the 3–5-MHz range.
Highlights
Over the past decades, the use of bubbles in the ultrasound (US) diagnostic and therapeutic arsenal has increased[1,2,3,4,5]
The corresponding values of dilatational viscosity ranged from 5.10−10 Ns/m to 1.10−9 Ns/m
We showed that albumin NBs can be used effectively as cavitation nuclei, with inertial cavitation thresholds under 2 MPa
Summary
The use of bubbles in the ultrasound (US) diagnostic and therapeutic arsenal has increased[1,2,3,4,5] They can be used as ultrasound contrast agents (UCA) to enhance the performance of US imaging and to determine physiological properties, notably blood flow[6,7,8,9,10]. Bubbles are ideal carriers for therapeutic material[14,15] They can cluster in a targeted area and release their payload either naturally or under the action of an external stimulus such as US16. The strength of the bubbles in this case is to act as cavitation nuclei, reducing the required pressure to induce the desired mechanical effect. Cavitation can be obtained only in places reachable by the bubbles in circulation This is one of the main potential benefits of nanobubbles (NBs) in the therapeutic arsenal. Bubble-oscillation simulations were conducted with a modified Rayleigh-Plesset equation to determine the rheological parameters (dilatational viscosity and surface tension) of the manufactured NBs
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