Subharmonic aided pressure estimation for monitoring interstitial fluid pressure in tumours--in vitro and in vivo proof of concept.

The feasibility of using subharmonic aided pressure estimation (SHAPE) to noninvasively estimate interstitial fluid pressure (IFP) was studied. In vitro, radiofrequency signals, from 0.2 ml/l of Definity (Lantheus Medical Imaging, N Billerica, MA) were acquired within a water-tank with a Sonix RP ultrasound scanner (Analogic Ultrasound, Richmond, BC, Canada; fT/R=6.7/3.35 MHz and fT/R=10/5 MHz) and the subharmonic amplitudes of the signals were compared over 0-50 mmHg. In vivo, five swine with naturally occurring melanomas were studied. Subharmonic signals were acquired from tumours and surrounding tissue during infusion of Definity and compared to needle-based pressure measurements. Both in vitro and in vivo, an inverse linear relationship between hydrostatic pressure and subharmonic amplitude was observed with r(2)=0.63-0.95; p<0.05, maximum amplitude drop 11.36 dB at 10 MHz and -8 dB, and r(2) as high as 0.97; p<0.02 (10 MHz and -4/-8 dB most promising), respectively, indicating that SHAPE may be useful in monitoring IFP.