(G-266) Towards remote measurement of tissue pressure using ultrasound and phase-change contrast agents

Introduction:: The transition of liquid nanodroplet (ND) phase-change contrast agents (PCCAs) to gaseous microbubbles (MBs) is dependent upon sufficient ultrasound peak negative pressure, frequency, and ND size. Based on these parameters we can selectively trigger acoustic droplet vaporization of the PCCAs and correlate this activation threshold to the ambient pressure as a remote measurement of vascular tissue pressure. The relationship of the activation threshold to the peak negative pressure at multiple focal points, the number of cycles, and the number of frames were analyzed.


Materials and Methods:: Decafluorobutane NDs were formulated in house using the popular condensation method with a mean size of 540 nm as measured on a tunable resistive pulse sensing instrument (qNano Gold; Izon Science). The NDs were activated at body temperature in a flow phantom with a steady rate of 5.2 mL/min. ND activation was done using a previously optimized sequence and the resultant MBs were captured using a programmable ultrasound scanner (Vantage 256, Verasonics Inc) equipped with an L11-4v linear array. An automated pressure sweep was applied by gradually increasing peak negative focal pressures from 1 to 8 MPa. Grayscale ultrasound images were acquired at each step. Ultrasound pulse length and impact on PCCA activation was varied from 1.0, 2.5 and 5 cycles. The number of images per pressure increment used were 2 and 10 frames to see the effect on PCCA activation threshold. A total of three focused beams were used to activate at multiple focal positions. The aperture size for each focus was set so that the f-number was kept constant (f = 1). Mean ultrasound image intensity values were fit to two linear functions to determine the activation threshold offline using custom MATLAB software (MathWorks, Inc). The first section of the curve was fit to a constant function with a slope of zero to mimic the pre-activation section. The second section of the curve was fit to a linear function with a positive slope. The intersection of these two functions was estimated as the activation threshold.


Results, Conclusions, and Discussions:: The activation threshold was calculated and organized based on the number of ultrasound pulse cycles, frames, and foci count. With an increase in the number of pulse cycles, the uniformity of PCCA activation increases with depth. The number of frames did not significantly change the activation threshold (p = 0.85). Therefore, we can tune our ultrasound system according to the number of frames and underlying flow. Proper selection of multiple ultrasound focal positions allows uniform PCCA activation under flow conditions and throughout region-of-interest. Overall, the activation threshold of PCCAs is very flexible and dependent on key parameters such as the peak negative pressure of ultrasound exposure, number of cycles, ND size, number of foci, and ambient pressure. Activation at multiple foci with a constant f-number will also require pressure matching to account for increased pressure as depth increases. We must carefully select these parameters for remote tissue pressure estimation. Optimizing this activation sequence with size-isolated PCCAs and tuning the number of frames, peak negative pressure applied, and number of ultrasound cycles will improve ambient pressure estimation accuracy.


Acknowledgements (Optional): :

References (Optional): :