Pharmacokinetics of echocontrast agent infusion in a dog model

Ultrasound contrast agents (UCAs) have a distinct diagnostic impact on transcranial Doppler (TCD) and duplex sonography. In addition to the properties of the UCA and ultrasound imaging modes, the duration of contrast enhancement depends on the administration mode. Infusion of UCAs may be appropriate for prolonging the diagnostically useful time of elevated Doppler intensity. Five sedated dogs were investigated by TCD during infusion with SonoVue, a new UCA consisting of sulfur hexafluoride microbubbles. The infusion rate was varied, and the time-intensity curves were analyzed. Infusion rate of 70 ml/h provided a stable mean level of increased Doppler intensity up to 24 to 26 dB over baseline, whereas a rate of 35 ml/h did not result in a stable plateau (range 8-19 dB over baseline [5 minutes after starting time]). The maximum increases in Doppler mean intensity (18.2 dB [35 ml/h] and 25.6 dB [70 ml/h]) were significantly different (P = .025). Pharmacokinetic analysis of SonoVue during inflow (by exponential functional fitting of the time-mean intensity curves) and elimination (by linear regression analysis) revealed no dose-related differences. This study demonstrated a dose-dependent level of increased Doppler mean intensity within the brain circulation during infusion of SonoVue. Unlike the bell-shaped course of Doppler signal enhancement seen after bolus injection, infusion generates a stable plateau, which is an important prerequisite for more advanced contrast applications.