A multivessel model describing replenishment kinetics of ultrasound contrast agent for quantification of tissue perfusion

To improve the quantification of tissue perfusion using intermittent sonography, a new model describing replenishment kinetics of microbubbles is proposed. The new approach takes into account the variability of blood flow velocities found in vivo, especially in tumors, and consistently describes the refilling process of microbubbles. Based upon this model, blood volume, blood velocity, blood flow and perfusion in 17 experimental tumors were calculated, and compared with the results obtained with the established, phenomenologically derived exponential kinetic model. In contrast to the existing model, our approach describes tissue vascularization more physiologically and allows deduction of a consistent new hyperbolic model for quantification of intermittent sonography. Blood volume and mean blood velocity did significantly correlate between both the new and the established model (k=0.99; k=0.94, both p<0.001). However, mean tumor blood velocity was lower (-19%, p<0.01) with the established model compared to the newly developed model. In addition, the range and distribution of blood flow velocities found in vivo can be estimated with the new model. Furthermore, it uses simpler mathematical fitting routines and allows easier data acquisition, which may allow a more practicable clinical application of intermittent sonography. In conclusion, a more valid, detailed and accurate calculation of perfusion parameters, especially of tumors, can be derived in vivo with the new multivessel model of intermittent sonography.