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

Bar Glickstein, Ramona Aronovich, Yi Feng, Tali Ilovitsh

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

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.

Original languageEnglish
Article number20664
JournalScientific Reports
Volume12
Issue number1
DOIs
StatePublished - 30 Nov 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022, The Author(s).

Funding

This work was supported by the Israel Science Foundation (Grant Numbers 3450/20 and 192/22), the Israel Ministry of Science & Technology (Grant Number 101716), an ERC StG Grant No. 101041118 (NanoBubbleBrain), a Zimin Institute grant, and was partially supported by a grant from the Nicholas and Elizabeth Slezak Super Center for Cardiac Research and Biomedical Engineering at Tel Aviv University. The work was also supported by the National Natural Science Foundation of China (Grant Number 82061148015).

FundersFunder number
European Commission101041118
National Natural Science Foundation of China82061148015
Israel Science Foundation3450/20, 192/22
Tel Aviv University
Ministry of science and technology, Israel101716
Nicholas and Elizabeth Slezak Super Center for Cardiac Research and Biomedical Engineering

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