Abstract
Purpose
Ultrasound contrast agents (UCAs) enable contrast-enhanced imaging via nonlinear microbubble oscillations, but repeated exposure can deplete the local bubble population and bias perfusion measurements. Conversely, in microbubble-assisted therapies, controlled depletion may be desirable. While destruction is known to increase with peak negative pressure and pulse duration and to decrease with transmit frequency, the role of pulse repetition frequency (PRF) under flow remains incompletely quantified.
Methods
We developed an acoustic monitoring framework to characterize PRF-dependent microbubble destruction in a vessel phantom. The destruction pulses (3 or 10 MHz; 1 or 3 cycles; 0.5–2.5 MPa peak negative pressure) were applied at PRFs of 0.125–16 kHz, while a 25-MHz transducer continuously recorded downstream M-mode data. Depth-integrated time-intensity curves (TICs) and their time integrals (integrated TIC, ITIC) captured the transition from baseline to depletion. ITICs were described using a simple exponential model, yielding a transient depletion rate constant (
b
) that provides a kinetic dose-rate descriptor, and a stable destruction percentage (DP) that reflects steady-state survival after replenishment.
Results
Both
b
and DP increased monotonically with PRF, with stronger effects at lower destruction-pulse frequency, higher pressure, and longer pulses. However,
b
did not uniquely predict DP, indicating that replenishment and exposure history shape steady-state depletion.
Conclusion
These metrics provide practical guidance for selecting PRF to preserve contrast signals in imaging or to achieve controlled depletion in therapeutic pulse sequences.