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Incident acoustic output (IAO) dependent subharmonic signal amplitudes from ultrasound contrast agents can be categorized into occurrence, growth or saturation stages. Subharmonic aided pressure estimation (SHAPE) is a technique that utilizes growth stage subharmonic signal amplitudes for hydrostatic pressure estimation. In this study, we developed an automated IAO optimization algorithm to identify the IAO level eliciting growth stage subharmonic signals and also studied the effect of pulse length on SHAPE. This approach may help eliminate the problems of acquiring and analyzing the data offline at all IAO levels as was done in previous studies and thus, pave the way for real-time clinical pressure monitoring applications. The IAO optimization algorithm was implemented on a Logiq 9 (GE Healthcare, Milwaukee, WI) scanner interfaced with a computer. The optimization algorithm stepped the ultrasound scanner from 0% to 100% IAO. A logistic equation fitting function was applied with the criterion of minimum least squared error between the fitted subharmonic amplitudes and the measured subharmonic amplitudes as a function of the IAO levels and the optimum IAO level was chosen corresponding to the inflection point calculated from the fitted data. The efficacy of the optimum IAO level was investigated for in vivo SHAPE to monitor portal vein (PV) pressures in 5 canines and was compared with the performance of IAO levels, below and above the optimum IAO level, for 4, 8 and 16 transmit cycles. The canines received a continuous infusion of Sonazoid microbubbles (1.5 μl/kg/min; GE Healthcare, Oslo, Norway). PV pressures were obtained using a surgically introduced pressure catheter (Millar Instruments, Inc., Houston, TX) and were recorded before and after increasing PV pressures. The experiments showed that optimum IAO levels for SHAPE in the canines ranged from 6% to 40%. The best correlation between changes in PV pressures and in subharmonic amplitudes (r=-0.76; p=0.24), and between the absolute PV pressures and the subharmonic amplitudes (r=-0.89; p<0.01) were obtained for the optimized IAO and 4 transmit cycles. Only for the optimized IAO and 4 transmit cycles did the subharmonic amplitudes differ significantly (p<0.01) before and after increasing PV pressures. A new algorithm to identify optimum IAO levels for SHAPE has been developed and validated with the best results being obtained for 4 transmit cycles. The work presented in this study may pave the way for real-time clinical applications of estimating pressures using the subharmonic signals from ultrasound contrast agents., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The efficacy of using subharmonic emissions from Sonazoid microbubbles (GE Healthcare, Oslo, Norway) to track portal vein pressures and pressure changes was investigated in 14 canines using either slow- or high-flow models of portal hypertension (PH). A modified Logiq 9 scanner (GE Healthcare, Milwaukee, WI, USA) operating in subharmonic mode (f(transmit): 2.5 MHz, f(receive): 1.25 MHz) was used to collect radiofrequency data at 10-40% incident acoustic power levels with 2-4 transmit cycles (in triplicate) before and after inducing PH. A pressure catheter (Millar Instruments, Inc., Houston, TX, USA) provided reference portal vein pressures. At optimum insonification, subharmonic signal amplitude changes correlated with portal vein pressure changes; r ranged from -0.82 to -0.94 and from -0.70 to -0.73 for PH models considered separately or together, respectively. The subharmonic signal amplitudes correlated with absolute portal vein pressures (r: -0.71 to -0.79). Statistically significant differences between subharmonic amplitudes, before and after inducing PH, were noted (p ≤ 0.01). Portal vein pressures estimated using subharmonic aided pressure estimation did not reveal significant differences (p > 0.05) with respect to the pressures obtained using the Millar pressure catheter. Subharmonic-aided pressure estimation may be useful clinically for portal vein pressure monitoring., (Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Abstract: Objective: To demonstrate the feasibility of simultaneous dual fundamental grayscale and subharmonic imaging on a modified commercial scanner. Motivation: The ability to generate signals at half the insonation frequency is exclusive to ultrasound contrast agents (UCA). Thus, subharmonic imaging (SHI; transmitting at f 0 and receiving at f 0/2) provides improved visualization of UCA within the vasculature via suppression of the surrounding tissue echoes. While this capability has proven useful in a variety of clinical applications, the SHI suppression of surrounding tissue landmarks (which are needed for sonographic navigation) also limits it use as a primary imaging modality. In this paper we present results using a commercial ultrasound scanner modified to allow imaging in both grayscale (f 0 =4.0MHz) and SHI (f 0 =2.5MHz, f 0/2=1.25MHz) modes in real time. Methods: A Logiq 9 ultrasound scanner (GE Healthcare, Milwaukee, WI) with a 4C curvilinear probe was modified to provide this capability. Four commercially available UCA (Definity, Lantheus Medical Imaging, North Billerica, MA; Optison, GE Healthcare, Princeton, NJ; SonoVue, Bracco Imaging, Milan, Italy; and Sonazoid, GE Healthcare, Oslo, Norway) were all investigated in vitro over an acoustic output range of 3.34MPa. In vivo the subharmonic response of Sonazoid was investigated in the portal veins of four canines (open abdominal cavity) and four patients with suspected portal hypertension. Results: In vitro, the four UCA showed an average maximum subharmonic amplitude of 44.1±5.4dB above the noise floor with a maximum subharmonic amplitude of 48.6±1.6dB provided by Sonazoid. The average in vivo maximum signal above the noise floor from Sonazoid was 20.8±2.3dB in canines and 33.9±5.2dB in humans. Subharmonic amplitude as a function of acoustic output in both groups matched the S-curve behavior of the agent observed in vitro. The dual grayscale imaging provided easier sonographic navigation, while the degree of tissue suppression in SHI mode varied greatly on a case by case basis. Conclusions: These results demonstrate the feasibility of dual grayscale and SHI on a modified commercial scanner. The ability to simultaneously visualize both imaging modes in real time should improve the applicability of SHI as a future primary clinical imaging modality. [Copyright &y& Elsevier]