Evaluation of blood flow in the cerebral microcirculation: analysis of the refill kinetics during ultrasound contrast agent infusion.

By means of harmonic imaging, it is possible to display brain perfusion qualitatively using ultrasound (US) contrast agent (UCA) bolus injection. With UCA continuous infusion reaching a steady state, mean microbubble velocity can be measured, analyzing the reappearance rate after microbubble destruction by US (refill kinetics). We performed an animal pilot study to investigate this new method for the assessment of brain perfusion. Using harmonic grey-scale imaging, five sedated male beagle dogs were investigated through the intact skull with increasing pulsing intervals (250 to 8000 ms) and three UCA infusion rates (0.5, 1.0 and 1.5 mL/min of Optison). Cerebral blood flow was increased by acetazolamide (30 mg/kg BW). Intensity vs. pulsing interval curves were analyzed using an exponential curve fit [I(t) = A(1-e(-beta t))] and parameters of the curve were compared. We found that increasing the pulsing interval above 4000 ms led to no further increase of echo enhancement for infusion rates. Mean beta values were not influenced by infusion rate (p = 0.25 and p = 0.55). Mean F values increased nonsignificantly with rising infusion rate (p = 0.25 and p = 0.86). Acetazolamide led to an increase of mean beta and F values (p = 0.18 and p = 0.025, respectively). It is possible to evaluate changes in brain perfusion through the intact skull by analyzing the UCA refill kinetics after US-induced microbubble destruction.