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This is the peer reviewed version of the following article: Gupta, I., Eisenbrey, J., Stanczak, M., Sridharan, A., Dave, J., Liu, J. -., . . . Forsberg, F. (2017). Effect of pulse shaping on subharmonic aided pressure estimation in vitroand in vivo. Journal of Ultrasound in Medicine, 36(1), 3-11, which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.


OBJECTIVES: Subharmonic imaging (SHI) is a technique that uses the nonlinear oscillations of microbubbles when exposed to ultrasound at high pressures transmitting at the fundamental frequency ie, f

METHODS: Eight waveforms with different envelopes were optimized with respect to acoustic power at which the SHAPE study is most sensitive. The study was run with four input transmit cycles, first in vitro and then in vivo in three canines to select the waveform that achieved the best sensitivity for detecting changes in portal pressures using SHAPE. A Logiq 9 scanner with a 4C curvi-linear array was used to acquire 2.5 MHz radio-frequency data. Scanning was performed in dual imaging mode with B-mode imaging at 4 MHz and a SHI contrast mode transmitting at 2.5 MHz and receiving at 1.25 MHz. Sonazoid, which is a lipid stabilized gas filled bubble of perfluorobutane, was used as the contrast agent in this study.

RESULTS: A linear decrease in subharmonic amplitude with increased pressure was observed for all waveforms (r from -0.77 to -0.93; P < .001) in vitro. There was a significantly higher correlation of the SHAPE gradient with changing pressures for the broadband pulses as compared to the narrowband pulses in both in vitro and in vivo results. The highest correlation was achieved with a Gaussian windowed binomial filtered square wave with an r-value of -0.95. One of the three canines was eliminated for technical reasons, while the other two produced very similar results to those obtained in vitro (r from -0.72 to -0.98; P

CONCLUSIONS: Using this waveform is an improvement to the existing SHAPE technique (where a square wave was used) and should make SHAPE more sensitive for noninvasively determining portal hypertension.

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