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 language | English |
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Article number | 20664 |
Journal | Scientific Reports |
Volume | 12 |
Issue number | 1 |
DOIs | |
State | Published - 30 Nov 2022 |
Externally published | Yes |
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).
Funders | Funder number |
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European Commission | 101041118 |
National Natural Science Foundation of China | 82061148015 |
Israel Science Foundation | 3450/20, 192/22 |
Tel Aviv University | |
Ministry of science and technology, Israel | 101716 |
Nicholas and Elizabeth Slezak Super Center for Cardiac Research and Biomedical Engineering |