Ultrasound thrombolysis stands out among various treatment methods due to its safety and high efficiency. While the cavitation and mechanical mechanisms underlying this technique are well-established, the impact of the concentration-dependent strain hardening properties of thrombotic biomaterials on ultrasound-induced shockwave effects remains a subject of considerable interest. Furthermore, the extremely short time window for effective clinical intervention necessitates precise spatial localization of rapidly formed shockwaves and determination of their energy thresholds for optimizing treatment protocols.
Considering that the primary mechanical properties of blood clots are dominated by the fibrin network, their stress-strain relationship exhibits a pronounced dependence on fibrin concentration. A power-law constitutive equation capable of characterizing the progressive hardening characteristics of clots was proposed here, based on results obtained from quasi-static compression tests performed on clots with varying fibrin concentrations. By employing the wave speed alterations induced by strain-hardening characteristics, which were incorporated into a third-order nonlinear ultrasound propagation wave equation, the dynamic characteristics underlying shock wave formation during ultrasound propagation through clot media were examined via numerical simulations. Results revealed that the pronounced stress discontinuity preceding this process originated from a sudden displacement change caused by the clot's progressive hardening. To accurately pinpoint the initiation location, the Average Steepening Factor (ASF), based on threshold limitation, was employed for localization. However, this method was severely constrained by mesh convergence issues, and improvements in finite precision incurred exponential increases in computational time. In contrast, the Total Harmonic Distortion (THD), utilizing the extremum of frequency-domain energy for localization, demonstrated lower sensitivity to truncation errors and offered computational efficiency advantages. Parametric analysis indicated a maximum localization error of 2.55% between the two methods, with the peak stress determined by the THD criterion being significantly higher than that identified by the ASF method.
Based on experimentally fitted constitutive equations for different concentrations, numerical simulations of wave propagation indicated that increasing fibrin concentration delayed the shockwave formation position by 91.7% and increased the peak stress by 60% according to the THD criterion, due to fibrin concentration increasing from 10 mg/mL to 35 mg/mL. Corresponding fitting formulas were derived. Through real-time THD feedback and acoustic field parameter regulation, a theoretical basis is provided for the rapid localization and flexible control of shockwave effects in clinical ultrasound thrombolysis.