Imaging-Guided Dual-Target Neuromodulation of the Mouse Brain Using Array Ultrasound
Guofeng Li, Weibao Qiu, Jiehan Hong, Qiuju Jiang, Min Su, Peitian Mu, Ge Yang, Yongchuan Li, Congzhi Wang, Huailing Zhang, Hairong Zheng
IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control 2018, 65, 1583-1589 · 10.1109/tuffc.2018.2847252
Abstract
Neuromodulation is an important method for investigating neural circuits and treating neurological and psychiatric disorders. Multiple-target neuromodulation is considered an advanced technology for the flexible optimization of modulation effects. However, traditional methods such as electrical and magnetic stimulations are not convenient for multiple-target applications due to their disadvantages of invasiveness or poor spatial resolution. Ultrasonic neuromodulation is a new noninvasive method that has gained wide attention in the field of neuroscience, and it is potentially able to support multiple-target stimulation by allocating multiple focal points in the brain using an array transducer. However, there are no reports in the literature of the efficacy of this technical concept, and an imaging tool for localizing the stimulation area for evaluating the neural effects in vivo has been lacking. In this study, we designed and fabricated a new system specifically for imaging-guided dual-target neuromodulation. The design of the array transducer and overall system is described in detail. The stimulation points were selectable on a B-mode image. In vivo experiments were carried out in mice, in which forelimbs shaking responses and electromyography outcomes were induced by changing the stimulation targets. The system could be a valuable tool for imaging-guided multiple-target stimulation in various neuroscience applications.
Abstract via europepmc.
Exposures
Exposure 1: Target A: brain site selected as a sensitive ultrasound-responsive circuit (forelimb shaking response)
Target: other — “Target A, described only by stereotaxic coordinates (~4 mm anteroposterior from bregma, 3.5 mm lateral from midline), chosen in 'a relatively sensitive brain circuit responding to the ultrasound stimulus'; Target B (a non-exposure active control site) was located about 3 mm lateral to Target A”
Device: custom-built
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 5,000 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.013 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| 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 | |
| Pressure, domain unspecified (kPa) | 930 | ✓✓✓⚑ |
| Ispta, domain unspecified (W/cm²) | 0.123 | ✓✓✓ |
The pulse generator excited the dual-mode transducer with long pulses (about 13 ms) in the neuromodulation mode, versus short pulses (0.2 microseconds) in the imaging mode. The acoustic pressure (P0) was about 930 kPa, the pulse duration (T1) was 13 ms, and the stimulus interval (T2) between successive stimuli was 3 s. Stimulation was applied alternately to targets A and B.
Flags from extraction
exposures[0].target.terms— Paper gives only stereotaxic coordinates and a functional description ('a relatively sensitive brain circuit') for Target A, with no named anatomical structure, so target.terms is 'other'.exposures[0].unspecified_domain.pressure_kpa— Domain (free field vs in situ/through skull) is not stated for the 930 kPa pressure and 123 mW/cm2 Ispta values used for in vivo mouse brain stimulation.exposures[0].timing.waveform— Classified as 'continuous' because the paper describes a single uninterrupted 13 ms pulse (T1) repeated every 3 s (T2, stimulus interval), with no internal pulse-repetition structure described within the 13 ms burst; however this interpretation could not be independently corroborated with additional waveform detail.