Investigation of the relationship of nonlinear backscattered ultrasound intensity with microbubble concentration at low MI.

The aim of this study was to measure the relationship of image intensity with contrast agent concentration. In vitro experiments were performed with a flow phantom and a sulphur hexafluoride filled microbubble contrast agent (SonoVue) at different concentrations (0.004 per thousand to 4 per thousand) covering the range commonly encountered in clinical practice. The concentration of microbubbles in the contrast agent solutions was confirmed optically. Images were collected with a diagnostic ultrasound system (iU22, Phillips Medical Systems, Bothell, WA, USA) and with a nonlinear imaging technique (power modulation) at low mechanical index (MI=0.05) to avoid bubble destruction. The mean intensity within a region of interest was measured to produce time-intensity curves from linearized (absolute scale) data. The relationship of linearized image intensity to contrast agent concentration was found to be linear up to 1 per thousand and reached a plateau at approximately 2 per thousand. To operate in the linear range of the intensity-concentration relationship the contrast agent dose should be adjusted to avoid those high values in vivo and the highest dynamic range of the ultrasound system should be used to avoid unnecessary signal saturation.