Size matters: Micro- versus nanobubbles in ultrasound imaging and therapy.

This study investigates the reported ability of nanobubbles (<500 nanometers in diameter) to exhibit a comparable or superior acoustic response to microbubbles (>1 micrometer in diameter). Eight hypotheses were examined. Both the theoretical and experimental results supported only one hypothesis: The apparent echogenicity of nanobubbles under both linear and nonlinear imaging is due to the presence of preexisting microbubbles, which are not reliably detected by available nanoparticle sizing methods. There was no evidence to support the other hypotheses, although the possibility of microbubble formation due to bubble aggregation/coalescence or swelling due to gas absorption in vivo could not be completely ruled out. Nanobubbles may offer advantages in terms of circulatory stability and potential for therapeutic delivery compared with microbubbles, but these advantages must be weighed against the need to use higher bubble concentrations, higher ultrasound frequencies, and/or higher intensities to achieve equivalent imaging and/or therapeutic effects.