Development of multi-layer lateral-mode ultrasound needle transducer for brain stimulation in mice

Jin, Yao; Li, Yongchuan; Yang, Yanchao; Zou, Junjie; Guo, Tongtong; Bian, Tianyuan; Wang, Congzhi; Xiao, Yang; Niu, Lili; Ma, Teng; Zheng, Hairong

doi:10.1109/tbme.2019.2953295

Cited by 7 publications

(3 citation statements)

References 20 publications

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“…A study has reported that the diameter of the multi-layer lateral-mode ultrasound needle transducer can be as small as 1.65 mm, enabling multitarget ultrasound neuromodulation [30]. However, the maximum ultrasound pressure of the transducer is only 300 kPa, which is difficulty to open the BBB.…”

Section: Discussionmentioning

confidence: 99%

“…In 2019, Li et al fabricated a single-crystal transducer-based head-worn stimulator for awake mice stimulation [29]. In 2020, Jin et al manufactured a miniature ultrasound needle transducer for awake small animal neuromodulation [30]. In 2021, Kim et al developed and evaluated a wearable remote-controlled ultrasound device, which successfully stimulates the brain of a freely moving rat [31].…”

Section: Introductionmentioning

confidence: 99%

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Simultaneous multi-target ultrasound neuromodulation in freely-moving mice based on a single-element ultrasound transducer

He¹,

Zhu²,

Wu³

et al. 2023

J. Neural Eng.

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Objective: Ultrasound neuromodulation has become an emerging method for the therapy of neurodegenerative and psychiatric diseases. The phased array ultrasonic transducer enables multi-target ultrasound neuromodulation in small animals, but the relatively large size and mass and the thick cables of the array limit the free movement of small animals. Furthermore, spatial interference may occur during multi-target ultrasound brain stimulation with multiple micro transducers. Approach: In this study, we developed a miniature power ultrasound transducer and used the virtual source time inversion method and 3-D printing technology to design, optimize, and manufacture the acoustic holographic lens to construct a multi-target ultrasound neuromodulation system for free-moving mice. The feasibility of the system was verified by in vitro transcranial ultrasound field measurements, in vivo dual-target blood-brain barrier opening experiments, and in vivo dual-target ultrasound neuromodulation experiments. Main results: The developed miniature transducer has a diameter of 4.0 mm, a center frequency of 1.1 MHz, and a weight of 1.25 g. The developed miniature acoustic holographic lens had a weight of 0.019 g to generate dual-focus transcranial ultrasound. The ultrasonic field measurements’ results showed that the bifocal’s horizontal distance was 3.0 mm, the -6 dB focal spot width in the x-direction was 2.5 and 2.25 mm, and 2.12 and 2.24 mm in the y-direction. Finally, the in vivo experimental results showed that the system could achieve dual-target blood-brain barrier opening and ultrasound neuromodulation in freely-moving mice. Significance: The ultrasonic neuromodulation system based on a miniature single-element transducer and the miniature acoustic holographic lens could achieve dual-target neuromodulation in awake small animals, which is expected to be applied to the research of non-invasive dual-target ultrasonic treatment of brain diseases in awake small animals.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Simultaneous multi-target ultrasound neuromodulation in freely-moving mice based on a single-element ultrasound transducer

He¹,

Zhu²,

Wu³

et al. 2023

J. Neural Eng.

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show abstract

“…First, the form factors of conventional ultrasound transducers are typically large compared to the several millimeter-scale working distances of a typical high numerical aperture objective lens. 13 , 14 Second, the glass coverslip used in the cranial window model largely prevents the delivery of ultrasonic waves due to high acoustic impedance, which compromises target specificity by transforming the longitudinal wave into the shear wave. 15 , 16 Consequently, observing functional activities of neuronal cells under controlled ultrasound stimulation is technically challenging.…”

Section: Introductionmentioning

confidence: 99%

Implantable acousto-optic window for monitoring ultrasound-mediated neuromodulation in vivo

Lee

Choi

et al. 2022

Neurophoton.

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Significance: Ultrasound has recently received considerable attention in neuroscience because it provides noninvasive control of deep brain activity. Although the feasibility of ultrasound stimulation has been reported in preclinical and clinical settings, its mechanistic understanding remains limited. While optical microscopy has become the "gold standard" tool for investigating population-level neural functions in vivo, its application for ultrasound neuromodulation has been technically challenging, as most conventional ultrasonic transducers are not designed to be compatible with optical microscopy. Aim:We aimed to develop a transparent acoustic transducer based on a glass coverslip called the acousto-optic window (AOW), which simultaneously provides ultrasound neuromodulation and microscopic monitoring of neural responses in vivo. Approach:The AOW was fabricated by the serial deposition of transparent acoustic stacks on a circular glass coverslip, comprising a piezoelectric material, polyvinylidene fluoride-trifluoroethylene, and indium-tin-oxide electrodes. The fabricated AOW was implanted into a transgenic neural-activity reporter mouse after open craniotomy. Two-photon microscopy was used to observe neuronal activity in response to ultrasonic stimulation through the AOW.Results: The AOW allowed microscopic imaging of calcium activity in cortical neurons in response to ultrasound stimulation. The optical transparency was ∼40% over the visible and near-infrared spectra, and the ultrasonic pressure was 0.035 MPa at 10 MHz corresponding to 10 mW∕cm 2 . In anesthetized Gad2-GCaMP6-tdTomato mice, we observed robust ultrasoundevoked activation of inhibitory cortical neurons at depths up to 200 μm. Conclusions:The AOW is an implantable ultrasonic transducer that is broadly compatible with optical imaging modalities. The AOW will facilitate our understanding of ultrasound neuromodulation in vivo.

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Piezoelectric actuation combined with ultrasound for enhancing drug delivery in gastric mucosa phantom in vitro

Shen,

Peng,

Zhu

et al. 2023

Smart Mater. Struct.

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In recent years, treatments for gastrointestinal malignant tumors have attracted a lot of attention. However, due to size limitations and the working environment of gastrointestinal peristalsis, traditional treatment methods have poor efficacy. Herein, we proposed a novel drug release method of piezoelectric actuation combined with ultrasound in the endoscope biopsy channel. A bidirectional piezoelectric actuator was manufactured and inserted into the endoscope with an ultrasonic transducer, adjusting the distance between the transducer and the lesion. A gastric mucosa phantom was fabricated and a finite element (FE) model was established for ultrasound thermal calculation. For enhancing the drug release rate, a pulse-echo method was conducted using a Laboratory Virtual Instrument Engineering Workbench (LabVIEW) program for real-time monitoring and feedback. The results of FEM calculations show that the temperature in the phantom can reach the melting-phase transition temperature of the TSL (41 ± 1 °C). The drug release rate can increase from 2.2 × 10−4 mg min−1 to 39.2 × 10−4 mg min−1 with our actuator, the latter is nearly 18 times the former. Furthermore, the drug release rate can be increased to a maximum value of 45.8 × 10−4 mg min−1 by optimizing the driving parameter of our actuator. Therefore, our method has a bright application in targeted drug delivery of major gastrointestinal diseases in the future.

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Development of multi-layer lateral-mode ultrasound needle transducer for brain stimulation in mice

Cited by 7 publications

References 20 publications

Simultaneous multi-target ultrasound neuromodulation in freely-moving mice based on a single-element ultrasound transducer

Simultaneous multi-target ultrasound neuromodulation in freely-moving mice based on a single-element ultrasound transducer

Implantable acousto-optic window for monitoring ultrasound-mediated neuromodulation in vivo

Piezoelectric actuation combined with ultrasound for enhancing drug delivery in gastric mucosa phantom in vitro

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