Nanodroplet-Mediated Low-Energy Mechanical Ultrasound Surgery

Glickstein, Bar; Levron, Mika; Shitrit, Sarah; Aronovich, Ramona; Feng, Yi; Ilovitsh, Tali

doi:10.1016/j.ultrasmedbio.2022.02.018

Cited by 17 publications

(12 citation statements)

References 43 publications

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“…Introducing cavitation nuclei can help to reduce the energy threshold for cavitation and enhance the therapeutic outcome significantly [12] . In recent years, the acoustically sensitive perfluorocarbon (PFC) nanodroplets as small as a few hundreds of nanometers have attractively emerged as an alternative to conventional microbubbles in the enhanced HIFU treatment and ultrasound imaging due to their longer circulation lifetime and smaller size for significant enhanced permeability and retention (EPR) effects in vivo relative to microbubbles [13] .…”

Section: Introductionmentioning

confidence: 99%

On-demand regulation and enhancement of the nucleation in acoustic droplet vaporization using dual-frequency focused ultrasound

Zhao

Qin

Chen

et al. 2022

Ultrasonics Sonochemistry

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Section: Introductionmentioning

confidence: 99%

On-demand regulation and enhancement of the nucleation in acoustic droplet vaporization using dual-frequency focused ultrasound

Zhao

Qin

Chen

et al. 2022

Ultrasonics Sonochemistry

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“…Importantly, both steps were carried out while operating below an MI of 1.9, in accordance with Food and Drug Administration (FDA) guidelines and reduce the pressure threshold required for standard histotripsy by two orders of magnitude. There are two major differences compared to previous work 38 . First, a 1D fixed imaging array was previously used for ND activation.…”

Section: Introductionmentioning

confidence: 73%

Development of an ultrasound guided focused ultrasound system for 3D volumetric low energy nanodroplet-mediated histotripsy

Glickstein

Aronovich

Feng

et al. 2022

Sci Rep

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Low pressure histotripsy is likely to facilitate current treatments that require extremely high pressures. An ultrasound guided focused ultrasound system was designed to accommodate a rotating imaging transducer within a low frequency therapeutic transducer that operates at a center frequency of 105 kHz. The implementation of this integrated system provides real-time therapeutic and volumetric imaging functions, that are used here for low-cost, low-energy 3D volumetric ultrasound histotripsy using nanodroplets. A two-step approach for low pressure histotripsy is implemented with this dual-array. Vaporization of nanodroplets into gaseous microbubbles was performed via the 1D rotating imaging probe. The therapeutic transducer is then used to detonate the vaporized nanodroplets and trigger potent mechanical effects in the surrounding tissue. Rotating the imaging transducer creates a circular vaporized nanodroplet shape which generates a round lesion upon detonation. This contrasts with the elongated lesion formed when using a standard 1D imaging transducer for nanodroplet activation. Optimization experiments show that maximal nanodroplet activation can be achieved with a 2-cycle excitation pulse at a center frequency of 3.5 MHz, and a peak negative pressure of 3.4 MPa (a mechanical index of 1.84). Vaporized nanodroplet detonation was achieved by applying a low frequency treatment at a center frequency of 105 kHz and mechanical index of 0.9. In ex-vivo samples, the rotated nanodroplet activation method yielded the largest lesion area, with a mean of 4.7 ± 0.5 mm2, and a rounded shape. In comparison, standard fixed transducer nanodroplet activation resulted in an average lesion area of 2.6 ± 0.4 mm2, and an elongated shape. This hybrid system enables to achieve volumetric low energy histotripsy, and thus facilitates the creation of precise, large-volume mechanical lesions in tissues, while reducing the pressure threshold required for standard histotripsy by over an order of magnitude.

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“…The MB expansion ratio, defined as the maximal diameter divided by the resting MB diameter, was evaluated for a center frequency of 250 kHz and peak negative pressures (PNP) ranging from 0 to 800 kPa. The simulation parameters were described previously ( Glickstein et al, 2022 ). The initial MB resting diameter was set to 1.5 μm.…”

Section: Methodsmentioning

confidence: 99%

“…1 . This effect was recently shown to facilitate the delivery of large genes into cancer cells ( Ilovitsh et al, 2020 ), and for low energy mechanical ablation of tumors ( Bismuth et al, 2021 ; Glickstein et al, 2022 ). Given the advantages of low frequency insonation, and the growing interest in the use of low frequencies ( Ilovitsh et al, 2020 ; Bai et al, 2016 ; Zhang et al, 2021 ), there is a crucial need for studies on ways to optimize the relationship between molecule size and delivery efficacy upon low frequency sonoporation for effective drug delivery.…”

Section: Introductionmentioning

confidence: 99%

Efficacy optimization of low frequency microbubble-mediated sonoporation as a drug delivery platform to cancer cells

Eck¹,

Aronovich²,

Ilovitsh³

2022

International Journal of Pharmaceutics: X

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Nanodroplet-Mediated Low-Energy Mechanical Ultrasound Surgery

Cited by 17 publications

References 43 publications

On-demand regulation and enhancement of the nucleation in acoustic droplet vaporization using dual-frequency focused ultrasound

On-demand regulation and enhancement of the nucleation in acoustic droplet vaporization using dual-frequency focused ultrasound

Development of an ultrasound guided focused ultrasound system for 3D volumetric low energy nanodroplet-mediated histotripsy

Efficacy optimization of low frequency microbubble-mediated sonoporation as a drug delivery platform to cancer cells

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