On the implementation of an automated acoustic output optimization algorithm for subharmonic aided pressure estimation

Abstract

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.

Investigating the Efficacy of Subharmonic Aided Pressure Estimation for Portal Vein Pressures and Portal Hypertension Monitoring

“…One approach to circumvent this problem may require obtaining the subharmonic gradient between the portal vein and the hepatic vein, which is analogous to the HVPG measurements used clinically (Eisenbrey et al 2001b; 2011c). Further, the inability to operate in grayscale imaging mode during RF data acquisition may be addressed by the use of newly available dual and simultaneous B-mode and subharmonic imaging mode (Eisenbrey et al 2011a, Dave et al 2012b). Another factor in this study was the mid-line abdominal incision created for accessing the main portal vein to obtain reference portal vein pressures; but absolute portal vein pressures cannot be obtained otherwise.…”

Cavitation thresholds of contrast agents in an in vitro human clot model exposed to 120-kHz ultrasound

“…However, changes in dissolved gas saturation complicated threshold measurements by precipitation of bubbles from oversaturated HFFP or loss of ELIP echogenicity by gas dissolution into under saturated HFFP. While this relatively small change in static pressure is not expected to have a substantial effect on the BB thresholds (Bader et al, 2012), Dave et al (2013) found subharmonic emissions decreased linearly with increasing ambient pressure. Ganor et al (2005) concluded that this change in subharmonic emission was due in part to the reduction in steady-state bubble radius as a result of a higher compression force.…”

Relationship between cavitation and loss of echogenicity from ultrasound contrast agents

“…Sustained stable cavitation, which is characterized by subharmonic and ultraharmonic acoustic emissions from microbubbles, has been shown to facilitate penetration of thrombolytics into clots (Datta et al 2008, Hitchcock et al 2011) and delivery of therapeutic-loaded ELIP into tissue (Hitchcock et al 2010). The subharmonic response of UCAs has also been employed in subharmonic imaging to enhance the contrast to tissue ratio (Sridharan et al 2013) and to estimate blood pressure non-invasively (Dave et al 2013). Inertial cavitation, which is characterized by broadband acoustic emissions from inertially collapsing microbubbles, has been shown to facilitate ablation of cancerous tissue (Coussios et al 2007) and delivery of genes into tissue through extravasation (Bazan-Peregrino et al 2012).…”