Excitation threshold for subharmonic generation from contrast microbubbles

There is a growing interest in microbubble based ultrasound contrast imaging applications in the 5-15 MHz range. In this study, individual microbubbles were insonified at low pressures (≤ 25 kPa) using an "acoustic spectroscopy" approach which entailed transmitting a sequence of tone bursts with center frequencies ranging from 4 to 13.5 MHz. The fundamental (transmit) frequency radial excursion amplitude was calculated from the scattered signals to produce a resonance curve for each bubble. For diameters between 2.5 to 4 μm, 69% of Target-Ready MicroMarker™ (Bracco, Geneva; Visualsonics, Canada) exhibited asymmetric resonance, characterized by a skewing of the resonance curve and indicative of nonlinear behavior. For Definity™ (Lantheus Medical Imaging, N. Billerica, MA), these responses were observed for 8% of diameters between 1.7 to 3.1 μm. For the subset of bubbles exhibiting linear, symmetric resonance curves, resonant frequencies, shell elasticity, and viscosity values were estimated. Between 10 to 12 MHz, for example, Target-Ready MicroMarker between 2.7 to 3.3 μm in diameter was resonant, where Definity was resonant between 1.7 to 2.6 μm. From 4 to 13.5 MHz, Target-Ready MicroMarker is characterized by a stiffer shell (3 < χ(0) < 5) N/m than Definity (0.5 < χ(0) < 2.5) N/m, and distinct strain-softening and shear-thinning rheological behavior. For Definity, no clear strain or shear-rate dependence of the shell properties is evident.

Section: B Shell Elasticitymentioning

confidence: 99%

Section: B Shell Elasticitymentioning

confidence: 99%

Nonlinear resonance behavior and linear shell estimates for Definity™ and MicroMarker™ assessed with acoustic microbubble spectroscopy

Helfield

Goertz

2013

“…27 The damped natural frequency for unforced oscillations, x d , is related to the eigenfrequency of the system by the damping coefficient,…”

Section: Estimation Of the Shell Viscositymentioning

confidence: 99%

Impulse response method for characterization of echogenic liposomes

Raymond

Luan²,

Rooij³

et al. 2015

An optical characterization method is presented based on the use of the impulse response to characterize the damping imparted by the shell of an air-filled ultrasound contrast agent (UCA). The interfacial shell viscosity was estimated based on the unforced decaying response of individual echogenic liposomes (ELIP) exposed to a broadband acoustic impulse excitation. Radius versus time response was measured optically based on recordings acquired using an ultra-highspeed camera. The method provided an efficient approach that enabled statistical measurements on 106 individual ELIP. A decrease in shell viscosity, from 2.1 Â 10 À8 to 2.5 Â 10 À9 kg/s, was observed with increasing dilatation rate, from 0.5 Â 10 6 to 1 Â 10 7 s À1 . This nonlinear behavior has been reported in other studies of lipid-shelled UCAs and is consistent with rheological shear-thinning. The measured shell viscosity for the ELIP formulation used in this study [j s ¼ (2.1 6 1.0) Â 10 À8 kg/s] was in quantitative agreement with previously reported values on a population of ELIP and is consistent with other lipid-shelled UCAs. The acoustic response of ELIP therefore is similar to other lipid-shelled UCAs despite loading with air instead of perfluorocarbon gas. The methods described here can provide an accurate estimate of the shell viscosity and damping for individual UCA microbubbles.

“…For example, it has been previously reported that increasing the shear viscosity of the agent increases the threshold for subharmonic oscillations. 44 Changing the shell stiffness enhances the resonance frequency of the agent, and alters the range of sizes of bubbles that demonstrate the strongest nonlinear oscillations. 44 Two other parameters-the buckling-radius and break-up radiusare reported to strongly impact the predicted nonlinear response of the agent.…”

Section: Discussionmentioning

confidence: 99%

“…44 Changing the shell stiffness enhances the resonance frequency of the agent, and alters the range of sizes of bubbles that demonstrate the strongest nonlinear oscillations. 44 Two other parameters-the buckling-radius and break-up radiusare reported to strongly impact the predicted nonlinear response of the agent. 13, 45 Sun and colleagues have shown previously that choosing buckling and rupture radii close to the resting radius of the microbubble results in a stronger nonlinear response.…”

Section: Discussionmentioning

confidence: 99%

The response of phospholipid-encapsulated microbubbles to chirp-coded excitation: Implications for high-frequency nonlinear imaging

Shekhar

Doyley

2013

The current excitation strategy for harmonic and subharmonic imaging (HI and SHI) uses short sinebursts. However, alternate pulsing strategies may be useful for enhancing nonlinear emissions from ultrasound contrast agents. The goal of this study was to corroborate the hypothesis that chirp-coded excitation can improve the performance of high-frequency HI and SHI. A secondary goal was to understand the mechanisms that govern the response of ultrasound contrast agents to chirp-coded and sine-burst excitation schemes. Numerical simulations and acoustic measurements were conducted to evaluate the response of a commercial contrast agent (Targestar-P V R ) to chirp-coded and sine-burst excitation (10 MHz frequency, peak pressures 290 kPa). The results of the acoustic measurements revealed an improvement in signal-to-noise ratio by 4 to 14 dB, and a two-to threefold reduction in the subharmonic threshold with chirp-coded excitation. Simulations conducted with the Marmottant model suggest that an increase in expansion-dominated radial excursion of microbubbles was the mechanism responsible for the stronger nonlinear response. Additionally, chirp-coded excitation detected the nonlinear response for a wider range of agent concentrations than sine-bursts. Therefore, chirp-coded excitation could be a viable approach for enhancing the performance of HI and SHI.