The lytic recombinant tissue plasminogen activator (rt-PA) is the only drug approved by the Food and Drug Administration for treating ischemic stroke. Less than 40% of patients with large vessel occlusions who are treated with rt-PA have improved blood flow. However, up to 6% of all patients receiving rt-PA develop intracerebral hemorrhage. Predicting the efficacy of rt-PA treatment a priori could help guide therapeutic decision-making, such that rt-PA is administered only to those individuals who would benefit from this treatment. Clot composition and structure affect the lytic efficacy of rt-PA and have an impact on elasticity. However, the relationship between clot elasticity and rt-PA lytic susceptibility has not been adequately investigated. The goal of this study was to quantify the relationship between clot elasticity and rt-PA susceptibility in vitro. Human and porcine highly retracted and mildly retracted clots were fabricated in glass pipettes. The rt-PA lytic susceptibility was evaluated in vitro using the percent clot mass loss. The Young’s moduli of the clots were estimated using ultrasound-based single-track-location shear wave elasticity imaging. The percent mass loss in mildly retracted porcine and human clots (28.9 ± 6.1% and 45.2 ± 7.1%, respectively) were significantly higher (p < 0.05) than those in highly retracted porcine and human clots (10.9 ± 2.1% and 25.5 ± 10.0%, respectively). Furthermore, the Young’s moduli of highly retracted porcine and human clots (5.33 ± 0.92 kPa and 3.21 ± 1.97 kPa, respectively) were significantly higher (p < 0.05) than those of mildly retracted porcine and human clots (2.66 ± 0.55 kPa and 0.79 ± 0.21 kPa, respectively). The results revealed an inverse relationship between the percent clot mass loss and Young’s modulus. These findings motivate continued investigation of ultrasound-based methods to assess clot stiffness in order to predict rt-PA thrombolytic efficacy.

Predicting thrombolytic susceptibility to recombinant tissue plasminogen activator (rt-PA) a priori could help guide clinical decision-making during acute ischemic stroke treatment and avoid adverse off-target lytic effects. The composition and structure of clots impact their mechanical properties and rt-PA thrombolytic efficacy. The goal of this study was to determine the relationship between clot elasticity and rt-PA thrombolytic efficacy in vitro. Human and porcine retracted and unretracted clots were fabricated in glass pipettes. Clots were embedded in agar phantoms, and their Young’s moduli were estimated using single-track-location shear wave elasticity imaging. The rt-PA thrombolytic efficacy was evaluated in vitro using the percent clot mass loss. The Young’s moduli of unretracted porcine and human clots (1.68±0.18 kPa and 0.72±0.13 kPa, respectively) were significantly lower (p&lt;0.05) than those of retracted porcine and human clots (4.96±1.07 kPa and 3.38±1.82 kPa, respectively). The percent mass loss of unretracted porcine and human clots (28.9±6.1% and 45.2±7.1%, respectively) were significantly higher (p&lt;0.05) than those of retracted porcine and human clots (10.9±2.1% and 25.5±10.0%, respectively). The results revealed a linear inverse correlation between the Young’s moduli and percent clot mass loss (R2 = 0.95, p = 0.025), suggesting that clot stiffness may serve as a surrogate metric for rt-PA thrombolytic susceptibility.

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