Increasing specificity of contrast-enhanced ultrasound imaging using the interaction of quasi counter-propagating wavefronts: a proof of concept.

Detection methods implemented in present clinical ultrasound scanners for contrast-enhanced ultrasound imaging show high sensitivity but a rather poor specificity due to pseudo-enhancement (false detection of contrast agent) produced by nonlinear wave propagation. They all require linear ultrasound propagation to detect nonlinear scattering of contrast agent microbubbles. Even at low transmit pressure, nonlinear wave propagation occurs in regions perfused with contrast agent because contrast agent microbubbles can dramatically enhance the nonlinear elastic behavior of the medium. This image artifact hinders further development of contrast-enhanced ultrasound imaging toward reliable quantitative measurement of local concentration of contrast agent and blood perfusion kinetics. We propose in this manuscript a new detection method, with specific beamforming and pulsing scheme, that produces contrast images with highly reduced pseudo-enhancement. It is based on the interaction of two diverging wavefronts broadcasted by two single elements of a conventional probe array. The contrast image is formed line by line; one single image line is the line segment bisector defined by the centers of the two transmitting elements. Each image line is formed by a three-step pulse sequence: (1) transmission with one element, (2) transmission with the other element, and (3) transmission with both elements. The proof of principle is shown with numerical simulations and in vitro experiments. The method is implemented in a programmable ultrasound system and tested in a tissue-mimicking phantom containing a vessel filled with diluted contrast agent. At a given depth, increasing the distance between the two transmitting elements increases the angle describing the propagation directions of the two wavefronts. As a result, the nonlinear interaction between the two broadcasted waves is reduced. We show experimentally that increasing the distance between the transmitting elements from 0.6 to 24 mm reduces the amplitude of the pseudoenhancement at the far wall of the vessel relative to true contrast signal amplitude in the vessel by 12 dB, therefore improving specificity in the contrast-enhanced image.