Comparison of intermittent-bolus contrast imaging with conventional power Doppler sonography: quantification of tumour perfusion in small animals

Replenishment kinetics of microbubbles were adapted to a single bolus injection to investigate tumour angiogenesis in small animals with intermittent imaging, and to compare vascularisation parameters from this new approach with conventional power Doppler ultrasound (US). A reformulation of the imaging protocol and the derivation of perfusion parameters was necessary, taking into account the time-dependence of the systemic microbubble concentration after single bolus injection. Using this new method, tumour vascularisation was evaluated in 13 experimental murine tumours. Furthermore, parameters calculated with intermittent imaging after bolus injection of 100 microl Levovist were compared with parameters from the signal intensity-time curve. The results showed that quantifying tumour perfusion, blood volume and flow, as well as the assessment of the mean blood velocity (in m/s), is possible in tumours with a volume of more than 0.1 mL. In larger tumours, a lower perfusion was calculated than in smaller ones (k = -0.88; p < 0.001). Only limited correlations were found between conventional power Doppler US quantities and parameters of intermittent sonography: Perfusion correlated with the maximum signal intensity (k = 0.61, p < 0.05) and the gradient to maximum (k = 0.82, p < 0.01), full width-half maximum was associated with blood volume (k = 0.62, p < 0.05). We conclude that intermittent bolus contrast sonography allows the quantification of tumour perfusion, even in small animals, and the monitoring of basic antiangiogenic studies with perfusion parameters shows a higher significance than conventional power Doppler US.