An in vitro investigation into Lumason's utility for subharmonic-aided pressure estimation with direct comparison to Sonazoid and Definity

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Subharmonic-aided pressure estimation (SHAPE) with ultrasound contrast agents (UCAs) has shown promising results in vitro and in vivo. Most commercial UCAs show an inverse linear relationship between subharmonic signal and hydrostatic pressure. However, conflicting trends have been reported for Lumason. Thus, this study investigated the subharmonic (i.e., SHAPE) response of Lumason and directly compare to Sonazoid and Definity in a static and a dynamic in vitro system using a clinical Logiq E10 scanner. SHAPE signals were acquired (in triplicate) using a C1-6 probe (transmit/receive: 2.50/1.25 MHz) in increments of 10 mmHg from 0 to 200 mmHg in the static tank, and peak pressures of 10, 20, 30, and 45 mmHg in the dynamic system. Sonazoid and Definity maintained consistent inverse linearity in both static and dynamic conditions, with average sensitivities of −0.07 dB/mmHg (r = −0.88) and −0.04 dB/mmHg (r = −0.97) in the static tank, and −0.14 dB/mmHg (r = −0.86) and −0.10 dB/mmHg (r = −0.85) in the dynamic system, respectively. Lumason exhibited a tri-phasic behavior; from 0–90 mmHg, SHAPE increased with increasing hydrostatic pressure (0.07 dB/mmHg; r = 0.98), while from 90 to 140 mmHg, the response plateaued (r = 0.32), before decreasing with increasing pressure from 140 to 200 mmHg (−0.14 dB/mmHg; r = −0.95). The subharmonic response of Sonazoid and Definity continues to be well- understood, but further investigations into Lumason’s SHAPE response is needed before clinical translation.