Contrast enhanced ultrasound tomography by means of the cumulative phase delay between second harmonic and fundamental component

Standard dynamic contrast-enhanced ultrasound (DCE-US) imaging detects and estimates ultrasound-contrastagent (UCA) concentration based on the amplitude of the harmonic components generated during ultrasound (US) propagation through UCAs. However, harmonic generation is not specific to UCAs, as it also occurs for US propagating through tissue. Moreover, nonlinear artifacts affect standard DCE-US imaging, causing contrast to tissue ratio (CTR) reduction, and resulting in possible tissue misclassification and misinterpretation of UCA concentrations. Especially for US tomography, no contrast-specific modality exists. Recently, a new marker for UCAs was discovered. A cumulative phase delay (CPD) between the second harmonic (2H) and fundamental (F0) component is in fact observable for US propagating through UCAs, and is absent in tissue. In this paper, CPD based tomographic US images are presented and compared to standard US tomography. By testing its applicability on gelatin phantoms with cylindrical cavities filled with a SonoVue® UCA dilution, we showed that CPD tomography outperforms standard US tomography by speed of sound and dispersion analysis, yielding a superior CTR: 32.2 dB vs. 0.06 and 4.6 dB, respectively.