Analysis of refill curve shape in ultrasound contrast agent studies

Contrast destruction and replenishment by Flash Echo Imaging (FEI) (also referred to as interval or intermittent imaging) has been qualitatively and quantitatively used for tissue blood refill measurements. Many features and capabilities of contrast refill in tissue blood flow and perfusion remain to be elucidated. To aid the development and full reliable utilization of the technique in medical practice, in this paper we undertake physical and mathematical modeling to evaluate different measures derivable from FEI and to provide a basis for the further study of sensitivity and stability of such measures for the detection and measurement of various flow properties and abnormalities. A phantom was developed and used to conduct a dynamic contrast study. Refill curves were investigated as a means of calculating the mean transit time (MTT) and investigating other information that can be determined from their shape. Exponential and error function fits and the area above these curves were used to estimate MTT. The bubble disruption zone was visually measured and theoretically modeled. Computer simulated refill curves based on the flow phantom for different velocity ranges were then computed and compared to the experimental refill curves. The simulated refill curves closely matched the experimental curves in both shape and MTT. The simulated refill curves matched the shape of the experimental results for different velocity ranges. Another simulation examined how a real circulatory system might influence refill. Different refill curve shapes were obtained for different vascular models. Models including the large arteries and veins showed a much faster initial slope than models where the large vessels were not included. Likewise, simulated "shunting" displayed a different slope than models without "shunting" and specific portions of the refill curve that could maximally distinguish shunting. This computer simulation could lead to some experimental hypotheses about differences between normal and cancerous blood flow.