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

•Subharmonic aided pressure estimation of interstitial tumour pressure is verified.•Inverse relationship between hydrostatic/tumour pressure and subharmonic amplitude.•Maximum drop in amplitude in vitro 11.36dB at 10MHz and −8dB.•Most promising acoustic parameters in vivo 10MHz and −4/−8dB.•Subharmonic aided pressure estimation may be useful in monitoring cancer treatment. The feasibility of using subharmonic aided pressure estimation (SHAPE) to noninvasively estimate interstitial fluid pressure (IFP) was studied. In vitro, radiofrequency signals, from 0.2ml/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=6.7/3.35MHz and fT/R=10/5MHz) and the subharmonic amplitudes of the signals were compared over 0–50mmHg. 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 r2=0.63–0.95; p