Controlled ultrasound tissue erosion: The role of dynamic interaction between insonation and microbubble activity

Xu, Zhen; Fowlkes, J. Brian; Rothman, Edward D.; Levin, Albert M.; Cain, Charles A.

doi:10.1121/1.1828551

Cited by 178 publications

(162 citation statements)

References 32 publications

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“…In FUS-induced BBB opening, 20,[32][33][34][35][36][37] sonothrombolysis, [38][39][40][41][42] and histotripsy 43,44 studies, correlations between the cavitation activity measured using a single-element passive cavitation detector (PCD) and treatment outcome have been reported. Moreover, microbubble emissions have been used to select treatment pressures 36 and modulate them in real-time between subsequent therapy pulses 35 during FUS-induced BBB opening.…”

Section: Introductionmentioning

confidence: 99%

Experimental demonstration of passive acoustic imaging in the human skull cavity using CT‐based aberration corrections

Jones

O’Reilly

Hynynen³

2015

Medical Physics

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Purpose: Experimentally verify a previously described technique for performing passive acoustic imaging through an intact human skull using noninvasive, computed tomography (CT)-based aberration corrections Jones et al. [Phys. Med. Biol. 58, 4981-5005 (2013)]. Methods: A sparse hemispherical receiver array (30 cm diameter) consisting of 128 piezoceramic discs (2.5 mm diameter, 612 kHz center frequency) was used to passively listen through ex vivo human skullcaps (n = 4) to acoustic emissions from a narrow-band fixed source (1 mm diameter, 516 kHz center frequency) and from ultrasound-stimulated (5 cycle bursts, 1 Hz pulse repetition frequency, estimated in situ peak negative pressure 0.11-0.33 MPa, 306 kHz driving frequency) Definity™ microbubbles flowing through a thin-walled tube phantom. Initial in vivo feasibility testing of the method was performed. The performance of the method was assessed through comparisons to images generated without skull corrections, with invasive source-based corrections, and with water-path control images. Results: For source locations at least 25 mm from the inner skull surface, the modified reconstruction algorithm successfully restored a single focus within the skull cavity at a location within 1.25 mm from the true position of the narrow-band source. The results obtained from imaging single bubbles are in good agreement with numerical simulations of point source emitters and the authors' previous experimental measurements using source-based skull corrections O'Reilly et al. [IEEE Trans. Biomed. Eng. 61, 1285-1294]. In a rat model, microbubble activity was mapped through an intact human skull at pressure levels below and above the threshold for focused ultrasound-induced blood-brain barrier opening. During bursts that led to coherent bubble activity, the location of maximum intensity in images generated with CT-based skull corrections was found to deviate by less than 1 mm, on average, from the position obtained using source-based corrections. Conclusions: Taken together, these results demonstrate the feasibility of using the method to guide bubble-mediated ultrasound therapies in the brain. The technique may also have application in ultrasound-based cerebral angiography. C 2015 American Association of Physicists in Medicine.

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Section: Introductionmentioning

confidence: 99%

Experimental demonstration of passive acoustic imaging in the human skull cavity using CT‐based aberration corrections

Jones

O’Reilly

Hynynen³

2015

Medical Physics

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“…11 The cavitation associated with histotripsy effects is described as a "bubble cloud," which has only been observed at pressure excursions much greater than inertial cavitation thresholds determined for similar frequency and pulse lengths in water. 12,13 A bubble cloud may be initiated during any pulse in a sequence of thousands of pulses, 12 although all incident pulses are essentially identical. This observation is evidence that bubble cloud initiation is a probabilistic phenomenon.…”

Section: Introductionmentioning

confidence: 99%

Cavitation clouds created by shock scattering from bubbles during histotripsy

Maxwell

Wang

Cain

et al. 2011

The Journal of the Acoustical Society of America

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Histotripsy is a therapy that focuses short-duration, high-amplitude pulses of ultrasound to incite a localized cavitation cloud that mechanically breaks down tissue. To investigate the mechanism of cloud formation, high-speed photography was used to observe clouds generated during single histotripsy pulses. Pulses of 5À20 cycles duration were applied to a transparent tissue phantom by a 1-MHz spherically focused transducer. Clouds initiated from single cavitation bubbles that formed during the initial cycles of the pulse, and grew along the acoustic axis opposite the propagation direction. Based on these observations, we hypothesized that clouds form as a result of large negative pressure generated by the backscattering of shockwaves from a single bubble. The positive-pressure phase of the wave inverts upon scattering and superimposes on the incident negativepressure phase to create this negative pressure and cavitation. The process repeats with each cycle of the incident wave, and the bubble cloud elongates toward the transducer. Finite-amplitude propagation distorts the incident wave such that the peak-positive pressure is much greater than the peak-negative pressure, which exaggerates the effect. The hypothesis was tested with two modified incident waves that maintained negative pressure but reduced the positive pressure amplitude. These waves suppressed cloud formation which supported the hypothesis.

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“…Within solid organs (ie, prostate parenchyma, renal cortex), this process mechanically disrupts tissue structures such that the cumulative effect of multiple histotripsy bursts is conversion of the targeted tissue into a liquefied homogenate of subcellular debris. 2,3 Interestingly, some structures, such as the collecting system of the kidney, appear to be resistant to cavitational damage, while others, such as the renal medulla, necessitate greater numbers of histotripsy pulses to induce histologic injury, suggesting a varying threshold of cavitational effect based on tissue characteristics. 4 Previously, we have demonstrated that histotripsy is an effective noninvasive technology for prostate tissue ablation and debulking in the canine model.…”

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Histotripsy Homogenization of the Prostate: Thresholds for Cavitation Damage of Periprostatic Structures

Styn

Hall

Fowlkes

et al. 2011

Journal of Endourology

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Background and Purpose: Histotripsy is a noninvasive, pulsed ultrasound technology that produces mechanically homogenized tissue within targeted volumes. Previous work has demonstrated prostatic tissue debulking in a canine model. The aim was to establish safety thresholds by evaluating histologic changes of urinary sphincter, neurovascular bundle (NVB), and rectum after targeted histotripsy treatment of these critical structures. Materials and Methods: Rectum, urinary sphincter, and NVB in five anesthetized canines were targeted for histotripsy treatment (50 total points). Locations received 1k, 10k, or 100k acoustic pulses (4 microsecond, 1 MHz) at a repetition frequency of 500 Hz. Canine subjects were euthanized immediately (2), survived 3 days (1), or 2 weeks (3) after treatment. Prostates, periprostatic tissue, and rectum were harvested and processed for histology. Results: The sphincter was structurally intact with minimal muscle fiber disruption even after 100k pulses (n = 10). Undamaged nerves, arteries, and veins of the NVB were seen despite mechanical homogenization of surrounding loose connective tissue (n = 19). The rectum, however, exhibited dose-dependent damage (n = 20). 1k pulses yielded mild submucosal hemorrhage. 10k pulses resulted in moderate collagen disruption and focal mucosal homogenization. 100k pulses produced damage to the mucosa and muscularis propria with extensive hemorrhage and collagen disruption. One canine treated with 100k pulses needed early euthanasia (day 3) because of complications from a urine leak. Conclusions: Histotripsy histologic tissue effect varied based on targeted structure with substantial structural preservation of NVB and sphincter. Rectal subclinical damage was apparent after 1k pulses and increased in extent and severity with escalating doses. Future work will include assessment of functional outcomes and refinement of these initial safety thresholds.

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Controlled ultrasound tissue erosion: The role of dynamic interaction between insonation and microbubble activity

Cited by 178 publications

References 32 publications

Experimental demonstration of passive acoustic imaging in the human skull cavity using CT‐based aberration corrections

Experimental demonstration of passive acoustic imaging in the human skull cavity using CT‐based aberration corrections

Cavitation clouds created by shock scattering from bubbles during histotripsy

Histotripsy Homogenization of the Prostate: Thresholds for Cavitation Damage of Periprostatic Structures

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