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Towards real-time implementation of subharmonic aided pressure estimation (SHAPE) — How to Identify optimum acoustic output for SHAPE?

Pressure measurements within the chambers of the heart yield critical information for diagnosis and management of cardiac patients (∼92 million Americans), but the procedure used to gain these pressures, cardiac catheterization, is invasive and expensive. Subharmonic aided pressure estimation (SHAPE) may be able to estimate intra-cardiac pressures noninvasively, if the optimum incident acoustic output (IAO) for SHAPE can be established in real-time. Therefore, the objective of this work was to determine in real-time the optimum IAO for SHAPE. We developed a customized interface on a SonixTablet scanner (BK Ultrasound, Richmond, BC, Canada) using C/C++ and Qt libraries (The Qt Company, Oslo, Norway). In vitro experiments were conducted using a closed-loop flow system. Activated Definity (Lantheus Medical Imaging Inc, N. Billerica, MA, USA; 0.1 ml) was mixed with 750 ml isotonic diluent. A pressure catheter (Millar Inc., Houston, TX, USA) was used to acquire ambient pressure values. A pulsed Doppler gate was placed within the lumen of the vessel in the flow system, then the SHAPE algorithm was initiated (ftransmit: 5.6 MHz; chirp down transmit pulse; pulse inversion mode). The algorithm steps through all the available IAO levels, extracting and processing the subharmonic amplitude in real-time. The IAO level associated with the maximum derivative of the subharmonic amplitude is then chosen as the optimum IAO level. Simultaneous catheter pressure and subharmonic data were acquired at, below and above the optimum IAO level (10 secs; n = 3). Linear correlation between the subharmonic and catheter data was performed using Matlab (MathWorks, Natick, MA, USA). At the optimum IAO level the correlation coefficient between SHAPE and the pressure catheter data ranged between −0.6 and −0.9; for the IAO immediately below and above the optimum IAO, ranges were −0.4 to −0.8, and −0.6 to −0.8, respectively. In conclusion, optimum IAO level determination for insonating microbubbles to be utilized for SHAPE has been demonstrated; this will assist in real-time clinical applications.