Dynamic contrast enhanced ultrasound (DCE-US) imaging has the potential to provide quantitative information which is sensitive to tumour perfusion, an indicator for tumour response to radiotherapy. To increase the reproducibility of time intensity curve (TIC) characteristics, we are developing a 3D DCE-US imaging system. There are, however, many choices to be made in system design, such as whether to use plane wave (PWI) or focused imaging (FI), and the values to use for parameters such as focal depth (FD), F-number (F#), mechanical index (MI) and number of angles (NA) (for PWI). We evaluated the effect of such choices on TICs (we refer to time-amplitude curve (TAC) here), using a microvascular flow phantom containing similar to 100,000 parallel microtubes, each 200 mu m in diameter. DCE-US 2D images were obtained using a Vantage (Verasonics Inc.) and a pulse-inversion algorithm. 800 frames were recorded at 10 Hz for PWI and FI. All measurements were repeated 3 times, injecting 0.4 ml of contrast agent (Sonozoid) and changing one parameter at a time, using the values: FD = 20, 40 mm; F# = 2, 4; MI = 0.11, 0.15, 0.25; NA = 3, 7, 11. For a large region of interest which included the periphery of the phantom, TACs were sharp and single-peaked for F2 but broader and double-peaked for F4, consistent with F4 averaging over a greater focal volume than F2. Choosing a smaller more central ROI reduced the effect but did not eliminate it completely. Placing the focus deeper than the center reduced the TAC amplitude due to attenuation but also resulted in a flatter TAC. PWI amplitude was greatest for 3 angles with evidence that this may be due to side lobe artefacts added to the contrast signal. TAC characteristics are thus expected to be highly sensitive to imaging parameters. This should be considered in longitudinal studies.