Detection of contrast agent in perfused tissues has been an important research topic for many years. Currently available methods are mostly based on the strong nonlinear scattering of contrast agent microbubbles. These methods selectively extract those parts of the spectrum that show the largest difference in nonlinearity between contrast agent and tissue. The method introduced in this paper expands this extraction approach in that it additionally exploits differences in system behavior between tissue and contrast bubbles. The resonant nature of contrast bubbles implies that the response of a contrast bubble is stateful, i.e., the response not only depends on the current input, but also on all previous inputs. Tissue does not show this dependence on previous inputs. Our method is based on a 3 pulse design in which the echoes from 2 nonoverlapping pulses are subtracted from a third pulse. With this method we aim to separate and suppress those parts in an echo signal that originate from tissue while leaving the part originating from contrast bubbles relatively undisturbed. Simulation results show increases up to 30 dB in contrast-to-tissue ratio (CTR) with this method relative to single pulse echoes. This was confirmed in an in vitro experiment that showed an increase of approximately 12 dB in CTR.,
I E E E Transactions on Ultrasonics, Ferroelectrics and Frequency Control
Department of Cardio-Thoracic Surgery

Borsboom, J.M.G, Bouakaz, A, & de Jong, N. (2009). Pulse subtraction time delay imaging method for ultrasound contrast agent detection. I E E E Transactions on Ultrasonics, Ferroelectrics and Frequency Control, 56(6), 1151–1158. doi:10.1109/TUFFC.2009.1157