This project aims to monitor and quantify intra-cardiac pressures via contrast-enhanced subharmonic imaging. We have proposed subharmonic aided pressure estimation (SHAPE; U.S. Patent 6,302,845) utilizing microbubble-based contrast agent signals for the noninvasive estimation of hydrostatic blood pressures in the heart cavities and in this study implemented real-time SHAPE on a commercial US scanner. An experimental pulse-echo system for SHAPE was constructed based on two single element transducers assembled confocally at a 60° angle to each other. A transducer with a bandwidth of 38% and a center frequency of 2.2 MHz (Staveley, East Hartford, CT) was used as the transmitter and a second transducer with a bandwidth of 86% and a center frequency of 3.6 MHz (Etalon Inc., Lebanon, IN) was the receiver. Changes in first, second, and subharmonic amplitudes of 6 different US contrast agents were measured in vitro at hydrostatic pressures from 0 –186 mmHg, acoustic pressures from 0.35– 0.60 MPa and frequencies of 2.5– 6.6 MHz. The optimal parameters for SHAPE were determined using linear regression analysis and implemented on a Sonix RP scanner (Ultrasonix Medical Corp, Richmond, Canada). The real-time implementation of SHAPE was tested in vitro. Over the pressure range studied the 1st and 2nd harmonic amplitudes reduced ~2 dB for all US contrast agents. Over the same pressure range, the subharmonic amplitudes decreased by 10 –14 dB and excellent linear regressions were achieved with the hydrostatic pressure variations (r
2
>0.98, p < 0.001). The optimal sensitivity for SHAPE was achieved at a transmit frequency of 2.5 MHz (i.e., receiving at 1.25 MHz) at a 0.35 MPa acoustic pressure using Sonazoid (GE Healthcare, Oslo, Norway) which declined ~14.4 dB in vitro. A Sonix RP scanner was modified to implement SHAPE on a phased array transducer PA4 –2 with a frequency range from 1.5– 4.5 MHz. A pulse inversion technique was used and the subharmonic signals are displayed in real-time and can also be stored for off-line analysis. SHAPE offers the possibility of allowing pressure gradients in the heart to be obtained noninvasively. Future studies will include in vivo pressure measurements. Supported by AHA grant no 06554414 and NIH HL081892.
This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).
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