Our group (and others) has been developing contrast-enhanced subharmonic imaging (SHI) for improved depiction of tumor blood flow and to provide quantitative assessment of physiological parameters; in particular the noninvasive estimation of hydrostatic blood pressures in the heart cavities using subharmonic microbubble signals (a method known as SHAPE; U.S. Patent 6,302,845).
In SHI pulses are transmitted at one frequency but only echoes at half that frequency (i.e., the subharmonic) are received. Recently, software for real time SHI and SHAPE was implemented on several commercial ultrasound scanners. Fourteen women with 16 biopsy-proven breast lesions (4 malignant) participated in a SHI pilot study. The area under the ROC curve for the diagnosis of breast cancer was 0.64 for baseline, 0.67 with contrast enhanced power Doppler, 0.76 with mammography and 0.78 with SHI. Contrast enhancement was better with SHI than with power Doppler (p=0.004).
In 4 canines, in vivo SHAPE pressure measurements were acquired in the chambers of the heart and compared to an invasive pressure catheter. In the normal LV (pressure range 0-70mmHg) an r2 value of 0.83 was obtained (p<0.001), while in the RA (pressure range 0.5-3.5mmHg) a slightly lower r2 of 0.65 was observed (p<0.001) with resolution on the order of 10 and 2 mmHg in the LV and RA, respectively.
In conclusion, in vivo human and canine experiments have demonstrated the feasibility of performing breast SHI and cardiac SHAPE using commercial ultrasound scanners and the preliminary results are encouraging (SHAPE resolution on the order of 2-10mmHg).

This work was supported in part by U.S. Army Medical Research Material Command under DAMD17-00-1-0464 and W81XWH-08-1-0503 as well as AHA grant no 06554414, NIH HL081892 and GE Healthcare, Oslo, Norway.