Time-intensity based optoacoustic flow measurements with gold nanoparticles

The indicator-dilution theory has been used for flow rate measurements in various imaging modalities, including magnetic resonance imaging, computed tomography and ultrasound. The experimental procedure generally involves the injection of a dose of indicator (i.e., the contrast agent), after which the concentration of the agent is monitored as a function of time; it is therefore also known as the time-intensity method. Although the time-intensity method has been widely applied to other imaging modalities, it has not been demonstrated with optoacoustic imaging. In this study, we experimentally test the hypothesis that quantitative blood flow measurements are feasible with the time-intensity based method in optoacoustic imaging. Gold nanospheres (broad band absorption spectrum peaks at 520 nm) were used as the optoacoustic contrast agent. The imaging system consisted of a frequency-doubled Nd:YAG laser operating at 532 nm for optical illumination, and an ultrasonic single crystal transducer with a center frequency of 3.5 MHz and a focal depth of 7 cm for detection. The volumetric flow rate ranged from 0.23 to 4.29 ml/sec, and the volume of the mixing chamber was from 30 to 80 ml. Results show good agreement between the measured mean transit times and the predicted time constants (correlation coefficient higher than 0.88), thus demonstrating the feasibility of the time-intensity based flow measurement technique. In addition to describing the method and experimental results, issues regarding the system sensitivity and estimation of the dilution transfer function are also discussed.