Ultrasonic contrast agents have been used to enhance the acoustic backscattered intensity of blood and to assist the assessment of blood flow parameters. One example is the time-intensity method based on the indicator-dilution theory. In this case, a mixing chamber model can be employed to describe the concentration of the contrast agent as a function of time. By measuring the time intensities at both the input and output of the blood mixing chamber, blood flow information can be obtained if proper deconvolution techniques are applied. Note that most deconvolution techniques assume a linear and time invariant (LTI) system for the mixing of the contrast agent with blood. In this paper, the hypothesis that a blood mixing chamber is an LTI system was tested. Several aspects were studied. One aspect was the linear relationship between the concentration of the contrast agent and the backscattered intensity. The other aspect was the dependence of the derived time constants on the concentration. The concept of an effective mixing volume was also introduced and evaluated. Finally, the input and the output time constants were measured and compared to theory under the LTI assumption. Extensive experiments were performed. Two in vitro flow models were constructed and two contrast agents were used. Results indicated that the LTI assumption does not hold and quantitative flow estimation is generally not possible. Nonetheless, the indicator-dilution theory can still be applied if only relative measurements of the flow rate are required.
Reliability of cerebral blood flow measurements by transcerebral double-indicator dilution technique