PURPOSE: Subharmonic imaging is of interest for high frequency (>10 MHz) nonlinear imaging, because it can specifically detect the response of ultrasound contrast agents (UCA). However, conventional UCA produce a weak subharmonic response at high frequencies, which limits the sensitivity of subharmonic imaging. We hypothesized that modifying the size distribution of the agent can enhance its high-frequency subharmonic response. The overall goal of this study was to investigate size-manipulated populations of the agent to determine the range of sizes that produce the strongest subharmonic response at high frequencies (in this case, 20 MHz). A secondary goal was to assess whether the number or the volume-weighted size distribution better represents the efficacy of the agent for high-frequency subharmonic imaging. METHODS: The authors created six distinct agent size distributions from the native distribution of a commercially available UCA (Targestar-P®). The median (number-weighted) diameter of the native agent was 1.63 μm, while the median diameters of the size-manipulated populations ranged from 1.35 to 2.99 μm. The authors conducted acoustic measurements with native and size-manipulated agent populations to assess their subharmonic response to 20 MHz excitation (pulse duration 1.5 μs, pressure amplitudes 100-398 kPa). RESULTS: The results showed a considerable difference between the subharmonic response of the agent populations that were investigated. The subharmonic response peaked for the agent population with a median diameter of 2.15 μm, which demonstrated a subharmonic signal that was 8 dB higher than the native agent. Comparing the subharmonic response of different UCA populations indicated that microbubbles with diameters between 1.3 and 3 μm are the dominant contributors to the subharmonic response at 20 MHz. Additionally, a better correlation was observed between the subharmonic response of the agent and the number-weighted size-distribution (R2=0.98) than with the volume-weighted size distribution (R2=0.53). CONCLUSIONS: Modifying the size distribution of the agent appears to be a viable strategy to improve the sensitivity of high-frequency subharmonic imaging. In addition, when the size distribution of the UCA has not been suitably modified, the number-weighted size distribution is a useful parameter to accurately describe the efficacy of the agent for high-frequency subharmonic imaging.
PURPOSE: Subharmonic imaging is of interest for high frequency (>10 MHz) nonlinear imaging, because it can specifically detect the response of ultrasound contrast agents (UCA). However, conventional UCA produce a weak subharmonic response at high frequencies, which limits the sensitivity of subharmonic imaging. We hypothesized that modifying the size distribution of the agent can enhance its high-frequency subharmonic response. The overall goal of this study was to investigate size-manipulated populations of the agent to determine the range of sizes that produce the strongest subharmonic response at high frequencies (in this case, 20 MHz). A secondary goal was to assess whether the number or the volume-weighted size distribution better represents the efficacy of the agent for high-frequency subharmonic imaging. METHODS: The authors created six distinct agent size distributions from the native distribution of a commercially available UCA (Targestar-P®). The median (number-weighted) diameter of the native agent was 1.63 μm, while the median diameters of the size-manipulated populations ranged from 1.35 to 2.99 μm. The authors conducted acoustic measurements with native and size-manipulated agent populations to assess their subharmonic response to 20 MHz excitation (pulse duration 1.5 μs, pressure amplitudes 100-398 kPa). RESULTS: The results showed a considerable difference between the subharmonic response of the agent populations that were investigated. The subharmonic response peaked for the agent population with a median diameter of 2.15 μm, which demonstrated a subharmonic signal that was 8 dB higher than the native agent. Comparing the subharmonic response of different UCA populations indicated that microbubbles with diameters between 1.3 and 3 μm are the dominant contributors to the subharmonic response at 20 MHz. Additionally, a better correlation was observed between the subharmonic response of the agent and the number-weighted size-distribution (R2=0.98) than with the volume-weighted size distribution (R2=0.53). CONCLUSIONS: Modifying the size distribution of the agent appears to be a viable strategy to improve the sensitivity of high-frequency subharmonic imaging. In addition, when the size distribution of the UCA has not been suitably modified, the number-weighted size distribution is a useful parameter to accurately describe the efficacy of the agent for high-frequency subharmonic imaging.
Authors: David E Goertz; Emmanuel Cherin; Andrew Needles; Raffi Karshafian; Allison S Brown; Peter N Burns; F Stuart Foster Journal: IEEE Trans Ultrason Ferroelectr Freq Control Date: 2005-01 Impact factor: 2.725
Authors: Jeffrey A Ketterling; Jonathan Mamou; John S Allen; Orlando Aristizábal; Rene G Williamson; Daniel H Turnbull Journal: J Acoust Soc Am Date: 2007-01 Impact factor: 1.840
Authors: David E Goertz; Martijn E Frijlink; Dennie Tempel; Vijay Bhagwandas; Andries Gisolf; Robert Krams; Nico de Jong; Antonius F W van der Steen Journal: Ultrasound Med Biol Date: 2007-08-02 Impact factor: 2.998
Authors: Charles A Sennoga; James S M Yeh; Julia Alter; Eleanor Stride; Petros Nihoyannopoulos; John M Seddon; Dorian O Haskard; Joseph V Hajnal; Meng-Xing Tang; Robert J Eckersley Journal: Ultrasound Med Biol Date: 2012-03-06 Impact factor: 2.998
Authors: Himanshu Shekhar; Kenneth B Bader; Shenwen Huang; Tao Peng; Shaoling Huang; David D McPherson; Christy K Holland Journal: Phys Med Biol Date: 2016-12-21 Impact factor: 3.609
Authors: Madhuvanthi A Kandadai; Prithviraj Mukherjee; Himanshu Shekhar; George J Shaw; Ian Papautsky; Christy K Holland Journal: Biomed Microdevices Date: 2016-06 Impact factor: 2.838