High Speed Imaging of Bubble Clouds Generated in Pulsed Ultrasound Cavitational Therapy - Histotripsy

Xu, Zhen; Raghavan, Malini; Hall, Timothy L.; Chang, Ching-Wei; Mycek, Mary Ann; Fowlkes, J. Brian; Cain, Charles A.

doi:10.1109/tuffc.2007.504

Cited by 98 publications

(28 citation statements)

References 36 publications

(51 reference statements)

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“…The pressure threshold for this simulation was defined as the pressure required to expand an initial bubble to >15 μm in radius, to be consistent with the minimum resolution for optical images recorded experimentally. This criteria is more reasonable for histotripsy therapy than the commonly used criteria for inertial cavitation of R max >2 R 0, since previous work has shown that histotripsy bubbles must be sufficiently expanded to sizes much greater than 2R 0 , often >50 μm, in order to fractionate tissue (Parsons et al 2006a; Xu et al 2007; Vlaisavljevich et al 2013a; Vlaisavljevich et al 2014c).…”

Section: Methodsmentioning

confidence: 99%

“…Using the shock scattering mechanism, bubble clouds are initiated at negative pressures ranging from 10–28 MPa. Because of the complexity of the shock scattering process, multiple factors determine whether a cloud initiated, including the distribution of heterogeneous nuclei in the focal region, the size and shape of initial single bubbles, the number of cycles, the shock rise time, and the positive pressure amplitudes (Xu et al 2007; Maxwell et al 2010; Maxwell et al 2011b; Vlaisavljevich et al 2014b). Additionally, our previous study demonstrated that increases in tissue stiffness result in higher cloud initiation thresholds when using the shock scattering mechanism of bubble cloud formation (Vlaisavljevich et al 2014b).…”

Section: Introductionmentioning

confidence: 99%

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Effects of Ultrasound Frequency and Tissue Stiffness on the Histotripsy Intrinsic Threshold for Cavitation

Vlaisavljevich

Lin

Maxwell

et al. 2015

Ultrasound in Medicine & Biology

144

221

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Histotripsy is an ultrasound ablation method that depends on the initiation of a cavitation bubble cloud to fractionate soft tissue. Previous work has demonstrated a cavitation cloud can be formed by a single pulse with one high amplitude negative cycle, when the negative pressure amplitude directly exceeds a pressure threshold intrinsic to the medium. We hypothesize that the intrinsic threshold in water-based tissues is determined by the properties of the water inside the tissue and changes in tissue stiffness or ultrasound frequency will have a minimal impact on the histotripsy intrinsic threshold. To test this hypothesis, the histotripsy intrinsic threshold was investigated both experimentally and theoretically. The probability of cavitation was measured by subjecting tissue phantoms with adjustable mechanical properties and ex vivo tissues to a histotripsy pulse of 1–2 cycles produced by 345 kHz, 500 kHz, 1.5 MHz, and 3 MHz histotripsy transducers. Cavitation was detected and characterized by passive cavitation detection and high-speed photography, from which the probability of cavitation was measured vs. pressure amplitude. The results demonstrated that the intrinsic threshold (the negative pressure at which probability=0.5) is independent of stiffness for Young’s moduli (E) < 1 MPa with only a small increase (~2–3 MPa) in the intrinsic threshold for tendon (E=380 MPa). Additionally, results for all samples showed only a small increase of ~2–3 MPa when the frequency was increased from 345 kHz to 3 MHz. The intrinsic threshold was measured to be between 24.7–30.6 MPa for all samples and frequencies tested in this study. Overall, the results of this study indicate that the intrinsic threshold to initiate a histotripsy bubble cloud is not significantly impacted by tissue stiffness or ultrasound frequency in hundreds of kHz to MHz range.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Ultrasound Frequency and Tissue Stiffness on the Histotripsy Intrinsic Threshold for Cavitation

Vlaisavljevich

Lin

Maxwell

et al. 2015

Ultrasound in Medicine & Biology

144

221

View full text Add to dashboard Cite

show abstract

“…Histotripsy depends on the initiation and maintenance of a cavitation bubble cloud to produce mechanical tissue fractionation (Parsons et al , 2006a; Xu et al , 2005). In order to effectively fractionate tissue into accelluar debris, histotripsy requires bubbles to rapidly expand from nanometer-sized initial nuclei into large cavitation bubbles greater than ~50μm in diameter (Parsons et al , 2006a; Vlaisavljevich et al , 2013a; Xu et al , 2007). Using a pressure high enough to initiate a bubble cloud and expand bubbles to a sufficient size, histotripsy has been shown capable of completely fractionating soft tissue into a liquid-appearing homogenate with no cellular structures remaining, resulting in effective tissue removal (Hall et al , 2007; Roberts et al , 2006; Vlaisavljevich et al , 2013b; Xu et al , 2005).…”

Section: Introductionmentioning

confidence: 99%

Effects of tissue stiffness, ultrasound frequency, and pressure on histotripsy-induced cavitation bubble behavior

et al. 2015

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Histotripsy is an ultrasound ablation method that controls cavitation to fractionate soft tissue. In order to effectively fractionate tissue, histotripsy requires cavitation bubbles to rapidly expand from nanometer-sized initial nuclei into bubbles often larger than 50 microns. Using a negative pressure high enough to initiate a bubble cloud and expand bubbles to a sufficient size, histotripsy has been shown capable of completely fractionating soft tissue into acelluar debris resulting in effective tissue removal. Previous work has shown that the histotripsy process is affected by tissue mechanical properties with stiffer tissues showing increased resistance to histotripsy fractionation, which we hypothesize to be caused by impeded bubble expansion in stiffer tissues. In this study, the hypothesis that increases in tissue stiffness causes a reduction in bubble expansion was investigated both theoretically and experimentally. High speed optical imaging was used to capture a series of time delayed images of bubbles produced inside mechanically tunable agarose tissue phantoms using histotripsy pulses produced by 345 kHz, 500 kHz, 1.5 MHz, and 3 MHz histotripsy transducers. The results demonstrated a significant decrease in maximum bubble radius (Rmax) and collapse time (tc) with both increasing Young’s modulus and increasing frequency. Furthermore, results showed that Rmax was not increased by raising the pressure above the intrinsic threshold. Finally, this work demonstrated the potential of using a dual-frequency strategy to modulate the expansion of histotripsy bubbles. Overall, the results of this study improve our understanding of how tissue stiffness and ultrasound parameters affect histotripsy-induced bubble behavior and provide a rational basis to tailor acoustic parameters for treatment of the specific tissues of interest.

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“…As the tissue is fractionated, the ultrasound appearance becomes progressively hypoechoic. 6–9 Previous studies demonstrating the safety and efficacy of transabdominal histotripsy of the prostate in an in vivo canine benign prostatic hypertrophy model 10 led us to hypothesize that prostate histotripsy could potentially have a role in the focal management of PCa.…”

mentioning

confidence: 99%

Histotripsy Focal Ablation of Implanted Prostate Tumor in an ACE-1 Canine Cancer Model

et al. 2012

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Purpose Histotripsy is a nonthermal ablative focused ultrasound technology with possible future applications for prostate cancer focal therapy. We used the ACE-1 prostate tumor model and evaluated the feasibility of treating prostate tumors with histotripsy. Materials and Methods A total of 10 immunosuppressed (cyclosporine treated) canine subjects received transrectal ultrasound guided percutaneous intraprostatic injection of ACE-1 canine prostate cancer cells. Prostates were serially imaged with transrectal ultrasound to monitor tumor growth. Subjects were sham treated (3) or underwent transabdominal histotripsy of the prostate, which targeted implanted tumor and adjacent parenchyma using a 750 kHz piezoelectric ultrasound therapy transducer. Prostates were examined histologically to confirm tumor and the histotripsy treatment effect. Results ACE-1 tumors were visualized on transrectal ultrasound in all 10 subjects within 2 weeks of tumor injection. Lesions demonstrated growth in the prostatic capsule, glandular lobules, fibrous septa and periurethral stroma with significant desmoplastic reaction and areas of central necrosis on histology. Lymph node and/or pulmonary metastases developed in 4 subjects. Ultrasound tumor localization and initiation of cavitation during histotripsy therapy were feasible in all treated subjects. Histologically there was evidence of homogenization of tumor and prostatic parenchyma in all 4 acute subjects with necrosis and hemorrhage in the 3 chronic subjects. Conclusions This study shows the feasibility of histotripsy destruction of prostate tumors in a canine ACE-1 model. It suggests a potential role for histotripsy based focal therapy for prostate cancer. Further studies are needed to better characterize the effects of histotripsy on malignant tissues.

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High Speed Imaging of Bubble Clouds Generated in Pulsed Ultrasound Cavitational Therapy - Histotripsy

Cited by 98 publications

References 36 publications

Effects of Ultrasound Frequency and Tissue Stiffness on the Histotripsy Intrinsic Threshold for Cavitation

Effects of Ultrasound Frequency and Tissue Stiffness on the Histotripsy Intrinsic Threshold for Cavitation

Effects of tissue stiffness, ultrasound frequency, and pressure on histotripsy-induced cavitation bubble behavior

Histotripsy Focal Ablation of Implanted Prostate Tumor in an ACE-1 Canine Cancer Model

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