Histotripsy Thrombolysis on Retracted Clots

Abstract

Retracted blood clots have been previously recognized to be more resistant to drug-based thrombolysis methods, even with ultrasound and microbubble enhancements. Microtripsy, a new histotripsy approach, has been investigated as a non-invasive, drug-free, and image-guided method that uses ultrasound to break up clots with improved treatment accuracy and a lower risk of vessel damage when compared to the traditional histotripsy thrombolysis approach. Unlike drug-mediated thrombolysis, which is dependent on the permeation of the thrombolytic agents into the clot, microtripsy controls acoustic cavitation to fractionate clots. We hypothesize that microtripsy thrombolysis is effective on retracted clots and that the treatment efficacy can be enhanced using strategies incorporating electronic focal steering. To test our hypothesis, retracted clots were prepared in vitro and the mechanical properties were quantitatively characterized. Microtripsy thrombolysis was applied on the retracted clots in an in vitro flow model using three different strategies: single-focus, electronically-steered multi-focus, and a dual-pass multi-focus strategy. Results show that microtripsy was used to successfully generate a flow channel through the retracted clot and the flow was restored. The multi-focus and the dual-pass treatments incorporating the electronic focal steering significantly increased the recanalized flow channel size compared to the single-focus treatments. The dual-pass treatments achieved a restored flow rate up to 324 mL/min without cavitation contacting the vessel wall. The clot debris particles generated from microtripsy thrombolysis remained within the safe range. The results in this study show the potential of microtripsy thrombolysis for retracted clot recanalization with the enhancement of electronic focal steering.

Non-invasive, Rapid Ablation of Tissue Volume Using Histotripsy

“…When it is necessary to ablate a region that exceeds the electronic focal steering range, it is possible to combine electrical and mechanical focal steering in a manner similar to that developed by Zhang et al (2016) to cover the entire volume while maintaining a high ablation rate. This approach will likely prove useful for in vivo settings like abdominal targets which require a higher f-number than that used in the current study, resulting in a diminished maximum steering angle.…”

“…In these early proof of principle studies where a high treatment rate was not the primary objective, the ablation rate was a fairly modest 0.05 mL/min. In our group, Zhang et al (2016) demonstrated that histotripsy with electronic focal steering can be combined with mechanical focal steering, resulting in higher efficiency for thrombolysis applications than when mechanical steering is used alone; however, the steering range used for this application was small (± 1 mm).…”

Non-Invasive Thrombolysis Using Microtripsy in a Porcine Deep Vein Thrombosis Model

“…However, HIFU generally carries with it the potential for damage of surrounding tissue due to diffusive heating patterns (Church 2007). While all of the aforementioned technologies have shown very promising results in the treatment of DVT, microtripsy thrombolysis hold distinct advantages over other ultrasonic thrombolysis modalities in that it is non-invasive, non-thermal, does not require injection of microbubbles or other therapeutic agents and is also effective for retracted clot (Zhang et al 2015a; Zhang et al 2015c; Zhang et al 2016). …”

“…A dual-pass strategy, previously developed in our lab (Zhang et al 2016), was used for the thrombolysis treatments in this study. The thrombus was treated with microtripsy in two passes (Figure 3).…”

“…Microtripsy is a new histotripsy approach that has recently been evaluated for its use in thrombolysis (Zhang et al 2015a; Zhang et al 2015c; Zhang et al 2016). Microtripsy uses the intrinsic threshold mechanism where acoustic cavitation is generated via single-cycle ultrasound pulses with the negative pressure phase directly exceeding the cavitation threshold intrinsic to the media.…”