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Passive Cavitation Enhancement Mapping via an Ultrasound Dual-Mode phased array to monitor blood-brain barrier opening

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Abstract

Purpose

Focused ultrasound with the presence of microbubbles has been shown to temporarily open the blood-brain barrier (BBB), which offers the potential to improve central nervous system disease treatment. Since BBB opening also highly correlates with the microbubble-induced stable cavitation, in this study, we aim to realize and implement the construction of cavitation-related passive mapping under the structure of a dual-mode phased array structure for the guidance of the focused ultrasound BBB-opening treatment.

Methods

A sparse distributed (48 out of a total of 256) receiving configuration was implemented to be functioned as dual-mode transmitting and receiving in the structure. The centered transmission locates at 400 kHz, whereas its 0.5x subharmonics (200 kHz), fundamental (400 kHz), 1.5x ultraharmonic (600 kHz), and 2nd harmonics (800 kHz) have been received and characterized. We demonstrated the capability of correlating the signal intensity with a wide range of microbubble concentrations in the in-vitro setup. In in-vivo verifications, a total of 9 animal experiments have been conducted to implement the passive cavitation mapping to correlate the imaging intensity with the occurrence of the outcome to induce blood-brain barrier opening.

Results

Ultraharmonics provided superior sensitivity and detectability to microbubble-related cavitation activity than the other selected frequency band, suggesting the potential in predicting BBB opening outcomes based on the passive image.

Conclusion

Cavitation mapping implemented by dual-mode ultrasound phased array is feasible and can provide assure the treatment quality in opening the blood-brain barrier in the brain.

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Acknowledgements

This work was supported by the Ministry of Science and Technology (with the grant number of 108-2221-E-002 -176 -MY3 and 108-2221-E-002 -175 -MY3).

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Authors and Affiliations

  1. Department of Electrical Engineering, Chang Gung University, Taoyuan, Taiwan

    Trung Nguyen Hoang & Cheng-Kai Jan

  2. Department of Electrical Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taipei, Taiwan

    Hsiang-Ching Lin, Chih-Hong Tsai & Hao-Li Liu

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  1. Trung Nguyen Hoang
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Correspondence to Hao-Li Liu.

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H. L. Liu served as a technical consultant of NaviFUS Corp., Taiwan and currently holds a number of therapeutic ultrasound related patents.

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Hoang, T.N., Lin, HC., Tsai, CH. et al. Passive Cavitation Enhancement Mapping via an Ultrasound Dual-Mode phased array to monitor blood-brain barrier opening. J. Med. Biol. Eng. 42, 757–766 (2022). https://doi.org/10.1007/s40846-022-00735-2

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