Characterization of acoustic droplet vaporization in tissue-mimicking, fibrin-based hydrogels for microrheology applications

Ultrasound-induced vaporization of phase-shift droplets (PSDs) into microbubbles, termed acoustic droplet vaporization (ADV), has expanded biomedical applications. Here, we explored the potential of ADV as a high-resolution, on-demand microrheometer using theoretical and experimental methodologies. This approach could be used to characterize tissue elasticity at spatial resolutions unrealizable with conventional in situ techniques, thus assisting with identification of underlying pathologies. For theoretical studies, bubble dynamics were combined with appropriate material constitutive models accounting for viscoelasticity of the surrounding tissue. Experiments were conducted on submicron- and micron-sized, perfluoropentane PSDs embedded in fibrin-based hydrogels with varying shear elastic moduli (0.2 kPa–11 kPa) to mimic soft tissues. Experimental studies included optical high-speed imaging and acoustic interrogations to record radial dynamics and acoustic emissions of the ADV-bubbles, respectively. Radial dynamics and the acoustic emissions of microbubbles produced by ADV depended significantly on fibrin elasticity. For example, an increase in fibrin elastic modulus from ∼0.8 kPa to ∼6 kPa reduced the maximum expansion radius of the generated ADV-bubbles by 50%. This increase in elasticity significantly impacted both linear (e.g., fundamental) and nonlinear (e.g., subharmonic) acoustic responses of the ADV-bubbles, by up to 15 dB. These findings open doors to a novel ADV-assisted tissue characterization technique.