Abstract
Mechanical effects of microbubbles on tissues are central to many emerging ultrasound applications. Here, we investigated the acoustic radiation force a microbubble exerts on tissue at clinically relevant therapeutic ultrasound parameters. Individual microbubbles administered into a wall-less hydrogel channel (diameter: 25–100 µm, Young's modulus: 2–8.7 kPa) were exposed to an acoustic pulse (centre frequency: 1 MHz, pulse length: 10 ms, peak-rarefactional pressures: 0.6–1.0 MPa). Using high-speed microscopy, each microbubble was tracked as it pushed against the hydrogel wall. We found that a single microbubble can transiently deform a soft tissue-mimicking material by several micrometres, producing tissue loading–unloading curves that were similar to those produced using other indentation-based methods. Indentation depths were linked to gel stiffness. Using a mathematical model fitted to the deformation curves, we estimated the radiation force on each bubble (typically tens of nanonewtons) and the viscosity of the gels. These results provide insight into the forces exerted on tissues during ultrasound therapy and indicate a potential source of bio-effects.
Highlights
Microbubbles are increasingly used as a contrast agent in ultrasound imaging and as a therapeutic agent in ultrasound therapy
The microbubble shell consisted of three lipids (Avanti Polar Lipids Inc., Alabaster, AL, USA) from powder—dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidic acid (DPPA) and dipalmitolyphosphatidylethanolamineÀpolyethylene glycol 2000 (DPPE-PEG2000)—which were mixed and diluted with glycerol (5% v/v) and saline (80% v/v)
Sustained, localised and reversible material indentation resulting from the primary acoustic radiation force on single microbubbles has been observed in soft tissuemimicking materials when exposed to typical therapeutic ultrasound pulses
Summary
Microbubbles are increasingly used as a contrast agent in ultrasound imaging and as a therapeutic agent in ultrasound therapy. Imaging applications continue to expand and include super-resolution to identify single microbubbles at micrometre-scale spatial resolution (Christensen-Jeffries et al 2015; Errico et al 2015) and molecular imaging, whereby ligand-coated microbubbles bind to receptors expressed on vascular endothelial cells (Deshpande et al 2010; Abou-Elkacem et al 2015). In these applications, microbubbles increase the returned ultrasound signal by oscillating in response to the imaging pulse. The increased signal provides contrast to the surrounding tissue, thereby enabling the many imaging applications described
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