A new strategy to enhance cavitational tissue erosion using a high-intensity, initiating sequence

Xu, Zhen; Fowlkes, J. Brian; Cain, Charles A.

doi:10.1109/tuffc.2006.1665098

Cited by 44 publications

(6 citation statements)

References 37 publications

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“…As such, even with nanodroplets diffusing only to regions next to tumor vasculature, targeted histotripsy will destroy the tumor core, overcoming the limitation caused by the shallow penetration depth of nanodroplets. This hypothesis is supported by our previous studies showing that once the cavitation bubble cloud is initiated, the histotripsy process can be maintained at a much lower pressure than that needed for initiation 24. The ability of histotripsy alone to erode a tissue layer by layer has been demonstrated in excised tissue samples 26 and in vivo large animal models 27, 28.…”

Section: Introductionsupporting

confidence: 56%

Nanodroplet-Mediated Histotripsy for Image-guided Targeted Ultrasound Cell Ablation

Vlaisavljevich¹,

Durmaz²,

Maxwell³

et al. 2013

Theranostics

105

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This paper is an initial work towards developing an image-guided, targeted ultrasound ablation technique by combining histotripsy with nanodroplets that can be selectively delivered to tumor cells. Using extremely short, high-pressure pulses, histotripsy generates a dense cloud of cavitating microbubbles that fractionates tissue. We hypothesize that synthetic nanodroplets that encapsulate a perfluoropentane (PFP) core will transition upon exposure to ultrasound pulses into gas microbubbles, which will rapidly expand and collapse resulting in disruption of cells similar to the histotripsy process but at a significantly lower acoustic pressure. The significantly reduced cavitation threshold will allow histotripsy to be selectively delivered to the tumor tissue and greatly enhance the treatment efficiency while sparing neighboring healthy tissue. To test our hypothesis, we prepared nanodroplets with an average diameter of 204±4.7 nm at 37°C by self-assembly of an amphiphilic triblock copolymer around a PFP core followed by cross-linkage of the polymer shell forming stable nanodroplets. The nanodroplets were embedded in agarose tissue phantoms containing a sheet of red blood cells (RBCs), which were exposed to 2-cycle pulses applied by a 500 kHz focused transducer. Using a high speed camera to monitor microbubble generation, the peak negative pressure threshold needed to generate bubbles >50 μm in agarose phantoms containing nanodroplets was measured to be 10.8 MPa, which is significantly lower than the 28.8 MPa observed using ultrasound pulses alone. High speed images also showed cavitation microbubbles produced from the nanodroplets displayed expansion and collapse similar to histotripsy alone at higher pressures. Nanodroplet-mediated histotripsy created consistent, well-defined fractionation of the RBCs in agarose tissue phantoms at 10 Hz pulse repetition frequency similar to the lesions generated by histotripsy alone but at a significantly lower pressure. These results support our hypothesis and demonstrate the potential of using nanodroplet-mediated histotripsy for targeted cell ablation.

show abstract

Section: Introductionsupporting

confidence: 56%

Nanodroplet-Mediated Histotripsy for Image-guided Targeted Ultrasound Cell Ablation

Vlaisavljevich¹,

Durmaz²,

Maxwell³

et al. 2013

Theranostics

105

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show abstract

“…1 ) without inducing the shock scattering effect. A similar concept has been proposed in [28] where a short, high-intensity sequence of pulses is applied to initiate tissue erosion via inertial cavitation clouds and subsequent lower intensity pulses are employed to sustain the process. The main idea behind this method [28] is, however, to generate cavitation nuclei using high intensity ultrasound pulses which can provide cavitation seeds for the latter lower intensity pulses to sustain cavitation and erosion (i.e., focused on increasing the probability of tissue erosion), which is different to the concept proposed in the present study.…”

Section: Discussionmentioning

confidence: 99%

Control of the dynamics of a boiling vapour bubble using pressure-modulated high intensity focused ultrasound without the shock scattering effect: A first proof-of-concept study

Pahk

2021

Ultrasonics Sonochemistry

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Highlights A new histotripsy concept is proposed and demonstrated. The extent and lifetime of a boiling bubble can be controlled. Boiling bubbles formed by localised shockwave heating can merge together. The coalesced boiling bubble maintains at the focus until the end of the exposure. No shock scattering-induced cavitation clouds are produced with the proposed method.

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“…Histotripsy fractionates soft tissue by well-controlled acoustic cavitation using microsecond-long, high-intensity and focused ultrasound pulses (Xu et al 2004; Xu et al 2005; Xu et al 2006; Xu et al 2007; Xu et al 2008). The feasibility of using histotripsy as a noninvasive, drug-free, and image-guided thrombolysis technique has been demonstrated previously.…”

Section: Introductionmentioning

confidence: 99%

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

Zhang

Miller

Lin

et al. 2015

Ultrasound in Medicine & Biology

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Histotripsy thrombolysis is a noninvasive, drug-free and image-guided therapy that fractionates blood clots using well-controlled acoustic cavitation alone. Real-time quantitative feedback is highly desired during histotripsy thrombolysis treatment to monitor the progress of clot fractionation. Bubble-induced color Doppler (BCD) monitors the motion following cavitation generated by each histotripsy pulse, which has been shown in gel and ex vivo liver tissue to be correlated with histotripsy fractionation. In this paper we investigate the potential of BCD to quantitatively monitor histotripsy thrombolysis in real-time. To visualize clot fractionation, transparent three-layered fibrin clots were developed. Results show a coherent motion follows the cavitation generated by each histotripsy pulse with a push and rebound pattern. The temporal profile of this motion expanded and saturated as the treatment progressed. A strong correlation existed between the degree of histotripsy clot fractionation and two metrics extracted from BCD: time of peak rebound velocity (tPRV) and focal mean velocity at a fixed delay (Vf,delay). The saturation of clot fractionation (i.e., treatment completion) matched well with the saturations detected using tPRV and Vf,delay. The mean Pearson correlation coefficients between the progressions of clot fractionation and the two BCD metrics were 93.1% and 92.6% respectively. To validate the BCD feedback in in vitro clots, debris volume from histotripsy thrombolysis were obtained at different therapy doses and compared with Vf,delay. The increasing and saturation trends of debris volume and Vf,delay also had good agreement. Finally, a real-time BCD feedback algorithm to predict complete clot fractionation during histotripsy thrombolysis was developed and tested. This work demonstrated the potential of BCD to monitor histotripsy thrombolysis treatment in real-time.

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A new strategy to enhance cavitational tissue erosion using a high-intensity, initiating sequence

Cited by 44 publications

References 37 publications

Nanodroplet-Mediated Histotripsy for Image-guided Targeted Ultrasound Cell Ablation

Nanodroplet-Mediated Histotripsy for Image-guided Targeted Ultrasound Cell Ablation

Control of the dynamics of a boiling vapour bubble using pressure-modulated high intensity focused ultrasound without the shock scattering effect: A first proof-of-concept study

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

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