Development of multi-layer lateral-mode ultrasound needle transducer for brain stimulation in mice
Yao Jin, Teng Ma, Hairong Zheng, Yongchuan Li, Ye Yang, Junjie Zou, Tianxu Guo, Tianyuan Bian, Congzhi Wang, Yang Xiao, Lili Niu
IEEE Transactions on Biomedical Engineering 2019 · 10.1109/tbme.2019.2953295
Abstract
Ultrasound, a non-invasive stimulation method, has proved effective in neurostimulation. Previous studies have demonstrated that low-frequency ultrasound (less than 1 MHz) is preferable owing to better penetrability through tissue and skull. However, the large size of low-frequency transducers, which are used in ultrasound neurostimulation studies, makes it difficult to perform multiple-target neurostimulation, especially in small animals such as mice. In this paper, a proposed low-frequency ultrasound needle transducer based on the multi-layer lateral-mode coupling method with a miniature aperture of 0.6 mm × 0.6 mm and a thickness of 1.65 mm was designed and fabricated. The measured electrical impedance of the fabricated 8-layer lateral-mode PZT-5H ceramic was 50.76 Ω at a resonant frequency of 866 kHz. The -6 dB bandwidth of 8-layer lateral-mode transducer was 29% at a center frequency of 876 kHz. The maximum ultrasound peak pressure amplitude at 820 kHz reached approximately 300 kPa, 4-5 times higher than that of the single-layer thickness-mode transducer with 200 V input voltage. The ultrasound beam showed no attenuation and low shift through mouse skull. To verify the feasibility of using the needle transducer to perform multiple-target nerve stimulation in mice brains, we constructed an ultrasound stimulus system to simultaneously stimulate two areas (M2 and V1) of the mouse brain in vivo and detected the c-Fos expression by immunofluorescence to evaluate the effect of stimulation. The results showed that a high ultrasound peak pressure amplitude with this transducer configuration is useful for ultrasound neurostimulation and multiple-target stimulation in mice.
Abstract via europepmc.
Exposures
Exposure 1: M2 stimulation
Target: motor cortex — “motor cortex (M2)”
Device: custom-built · 8-layer lateral-mode PZT-5H needle transducer ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 820 | ✓✓✓ |
| Pulse duration (ms) | 0.1 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | not reported | ⚑ |
| Free-field pressure (kPa) | 240 | ✓✓✓⚑ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Pulsed ultrasound (820 kHz, 82 cycles per pulse, 1 kHz pulse repetition frequency, 500 pulses, a duty cycle of 10%) delivered through two needle transducers fixed on the head, simultaneously to M2 and V1. Mice were perfused after a 30 min recovery period.
Exposure 2: V1 stimulation
Target: primary visual cortex — “visual cortex (V1)”
Device: custom-built · 8-layer lateral-mode PZT-5H needle transducer ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 820 | ✓✓✓ |
| Pulse duration (ms) | 0.1 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 10pulse duration × PRF gives 10% | ✓✓✓ |
| Sonication duration (s) | not reported |
| Free-field pressure (kPa) | 240 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Pulsed ultrasound (820 kHz, 82 cycles per pulse, 1 kHz pulse repetition frequency, 500 pulses, a duty cycle of 10%) delivered through two needle transducers fixed on the head, simultaneously to M2 and V1. Mice were perfused after a 30 min recovery period.
Flags from extraction
exposures[0].timing.pulse_duration_ms— Pulse duration 0.1 ms is cycles per pulse (82) divided by frequency (820 kHz); not stated directly in ms.exposures[0].free_field.pressure_kpa— 240 kPa was measured in a water tank at 3 mm (150 V, 20 cycles); the in vivo sentence quotes the same 240 kPa without naming a domain.exposures[0].timing.sonication_duration_s— Train duration not stated; 500 pulses at 1 kHz is the only information.n_subjects— Six mice total: sham n=3, ultrasound n=3.exposures[0].target.terms— M2 and V1 stimulated simultaneously by two needle transducers; two exposures with identical parameters.anaesthesia— Freely moving mice per Fig. 5(c) legend; no anaesthesia mentioned.sham_type— Sham group described only as without ultrasound stimulation.