Difference-frequency ultrasound imaging with non-linear contrast

Conventional ultrasound imaging is based on the scattering of sound from inhomogeneities in the density and the speed of sound and is often used in medicine to resolve pathologic compared to normal tissue. Here we demonstrate a differencefrequency ultrasound (dfUS) imaging method that is based on the interaction of two sound pulses that propagate non-collinearly and intersect in space and time. The dfUS signal arises primarily from the second-order non-linear coefficient, a contrast mechanism that differs from linear and harmonic US imaging. The distinct contrast mechanism allows dfUS to image anatomic features that are not identifiable in conventional US images of salmon and pig kidney tissue. Further, dfUS produces enhanced contrast of glioblastoma tumor implanted in the mouse brain, revealing its potential for improving medical diagnosis. Progress towards a real-time system is discussed.