Real-Time Feedback of Histotripsy Thrombolysis Using Bubble-Induced Color Doppler

Zhang, Xi; Miller, Ryan M.; Lin, Kuang Wei; Levin, Albert M.; Owens, Gabe E.; Gurm, Hitinder S.; Cain, Charles A.; Xu, Zhen

doi:10.1016/j.ultrasmedbio.2014.12.006

Cited by 28 publications

(31 citation statements)

References 57 publications

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“…We are currently working on developing a new porcine model to form chronic thrombi inside femoral veins. We are also developing a real-time thrombolysis monitoring algorithm to adaptively adjust therapy doses and strategies for thrombi with different ages (Zhang et al 2015b; Zhang et al 2016). In some cases, the thrombi formed in human legs can be extended to over 10 cm long, whereas the thrombi formed in our study were less than 3 cm.…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

Macoskey

Ives

et al. 2017

Ultrasound in Medicine & Biology

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Histotripsy is a noninvasive therapeutic technique that uses ultrasound generated from outside the body to create controlled cavitation in targeted tissue, and fractionates it into acellular debris. We have developed a new histotripsy approach, termed microtripsy, to improve targeting accuracy and to avoid collateral tissue damage. This in vivo study evaluates the safety and efficacy of microtripsy for noninvasive thrombolysis in a porcine deep vein thrombosis (DVT) model. Acute thrombi were formed in left femoral veins of pigs (~35 kg) by occluding the vessel using two balloon catheters and infusing with thrombin. Guided by real-time ultrasound imaging, microtripsy thrombolysis treatment was conducted in 14 pigs. 10 pigs were euthanized on the same day (acute) and 4 at 2 weeks (subacute). To evaluate vessel damage, 30-min free-flow treatment in right femoral vein (no thrombus) was also conducted in 8 acute pigs. Blood flow was successfully restored or significantly increased after treatment in 13 out of the 14 pigs. The flow channels reopened by microtripsy had a diameter up to 64% of the vessel diameter (~6 mm). The average treatment time was 16 minute per cm-long thrombus. Only mild intravascular hemolysis was induced during microtripsy thrombolysis. No damage was observed on vessel walls after two weeks of recovery, venous valves were preserved, and there was no sign of pulmonary embolism. The results of this study indicate that microtripsy has the potential to be a safe and effective treatment for DVT in a porcine model.

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Section: Discussionmentioning

confidence: 99%

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

Zhang

Macoskey

Ives

et al. 2017

Ultrasound in Medicine & Biology

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“…The dose of 300 pulses per location used in this study was chosen empirically to ensure complete clot fractionation and is probably overdosed. As the clot properties can vary across patients and even an individual clot can be heterogeneous, we are investigating a new feedback method that can indicate the complete clot fractionation in real-time, which will allow us to adaptively apply the optimal dose at each treatment location during treatment [41, 42]. The treatment time can be further reduced by increasing the PRF, however higher PRF may increase the risk of heating the overlying tissue and lower treatment efficiency by introducing cavitation memory effect [39].…”

Section: Discussionmentioning

confidence: 99%

Noninvasive thrombolysis using histotripsy beyond the intrinsic threshold (microtripsy)

Zhang

Owens

Gurm

et al. 2015

IEEE Trans. Ultrason., Ferroelect., Freq. Contr.

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Histotripsy has been investigated as a non-invasive, drug-free, image-guided thrombolysis method that fractionates blood clots using acoustic cavitation alone. In previous histotripsy-mediated thrombolysis studies, cavitation clouds were generated using multi-cycle pulses and tended to form on vessel wall. To avoid potential cavitational damage to vessel wall, a new histotripsy approach, termed Microtripsy, has been recently discovered where cavitation is generated via an intrinsic-threshold mechanism using single-cycle pulses. We hypothesize that microtripsy can generate and confine cavitation in vessel lumen without contacting vessel wall, which results in recanalization within clot and potentially eliminating vessel damage. To test our hypothesis, microtripsy was investigated for clot recanalization in an in vitro flow model. Clots were formed inside a vessel phantom (6.5 mm inner diameter) in line with a flow system. Microtripsy was applied by a 1-MHz transducer at a pulse repetition frequency of 50 Hz with a peak negative pressure (P-) of 30 MPa or 36 MPa. To create a flow channel through a clot, the cavitation focus was scanned through the clot at an interval of 0.3 or 0.7 mm. The treated clots were 3D-scanned by a 20-MHz ultrasound probe to quantify the channels. Restored flow rates were measured and clot debris particles generated from the treatments were analyzed. In all treatments, cavitation cloud was consistently generated in the center of the vessel lumen without contacting the vessel wall. After each treatment, a flow channel was successfully generated through and completely confined inside the clot. The channels had a diameter up to 60 % of the vessel diameter with restored flow up to 500 mL/min. The debris particles were small with over 99.9% < 10 μm and the largest at 153 um. Each clot (2 cm long) was recanalized within 7 min. The size of the flow channels increased by using higher P- and was significantly larger by using the 0.3 mm scan interval than those using 0.7 mm. The results in this study show the potential of this new microtripsy thrombolysis method for fast, precise, and effective clot recanalization, minimizing risks of vessel damage and embolism.

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“…2011b). A new histotripsy approach, termed microtripsy, has been recently investigated for thrombolysis application to improve treatment precision and avoid potential vessel damage (Zhang et al 2015a; Zhang et al 2015b; Zhang et al 2015c). In microtripsy, a cavitation cloud is initiated via a single-cycle ultrasound pulse with only one high, negative pressure phase exceeding a very distinct negative pressure intrinsic threshold of the medium (Maxwell et al 2013; Lin et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Histotripsy Thrombolysis on Retracted Clots

Owens

Cain

et al. 2016

Ultrasound in Medicine & Biology

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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.

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Real-Time Feedback of Histotripsy Thrombolysis Using Bubble-Induced Color Doppler

Cited by 28 publications

References 57 publications

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

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

Noninvasive thrombolysis using histotripsy beyond the intrinsic threshold (microtripsy)

Histotripsy Thrombolysis on Retracted Clots

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