Methods are provided for automatic setting of parameters for contrast agent quantification. Various processes may improve quantification. For example, for consistency in contrast agent quantification, a gain or other setting of an ultrasound system is automatically determined in response to destruction of the contrast agent or at the initiation of the contrast agent quantification procedure. Automatic setting of an adaptive gain provides equalized image intensity for each repetition of a contrast agent quantification procedure based on a same triggering event, the destruction of contrast agent. By synchronizing the adaptive setting algorithms with contrast agent destruction, similar base line information is provided for each iteration of a contrast agent quantification procedure. As another example, the contrast agent gain setting treats acoustic signals representing tissue or other non-contrast agent structure as noise, mapping the tissue values to a substantially constant low value within the dynamic range. As yet another example, by segmenting out blood pools or other areas of contrast agent likely to have contrast agents even after destruction, the resulting gain is more likely sensitive to the detection of perfused contrast agents.