Miniature ultrasound ring array transducers for transcranial ultrasound neuromodulation of freely-moving small animals
Hyunggug Kim, Seongyeon Kim, Nam Suk Sim, Cristina Pasquinelli, Axel Thielscher, Jeong Ho Lee, Hyunjoo J. Lee
Brain Stimulation 2019, 12, 251-255 · 10.1016/j.brs.2018.11.007
Abstract
Background Current transcranial ultrasound stimulation for small animal in vivo experiment is limited to acute stimulation under anesthesia in stereotaxic fixation due to bulky and heavy curved transducers. Methods We developed a miniaturized ultrasound ring array transducer which is capable of invoking motor responses through neuromodulation of freely-moving awake mice. Results The developed transducer is a 32-element, 183-kHz ring array with a weight of 0.035 g (with PCB: 0.73 g), a diameter of 8.1 mm, a focal length of 2.3 mm, and lateral resolution of 2.75 mm. By developing an affixation scheme suitable for freely-moving animals, the transducer was successfully coupled to the mouse brain and induced motor responses in both affixed and awake states. Conclusion Ultrasound neuromodulation of a freely-moving animal is now possible using the developed lightweight and compact system to conduct a versatile set of in vivo experiments.
Abstract via europepmc.
Exposures
Exposure 1: Transcranial ultrasound stimulation of motor cortex (acute and freely-moving mice)
Target: motor cortex — “motor cortex”
Device: custom-built · 32-element, 183-kHz CMUT ring array transducer ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 183 | ✓✓✓ |
| Pulse duration (ms) | 4.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 200 | ✓✓✓ |
| Duty cycle (%) | 90pulse duration × PRF gives 90% | ✓✓✓ |
| Sonication duration (s) | 0.2 | ✓✓✓ |
| 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 | |
| Ispta, domain unspecified (W/cm²) | 0.0341, 0.0554swept | ✓?⚑ |
The CMUT array was biased at DC bias voltage of 100 V and driven with AC peak-to-peak voltage of 80 V at 183 kHz. Each stimulation trial consisted of 40-pulses of 90% duty cycle at a pulse repeat frequency (PRF) of 200 Hz, and each 4.5-ms long pulse consisted of 756 pulses of ultrasound. At each intensity, approximately 25 stimulation trials were conducted over 4 min, with success rate measured by adjusting the AC voltage to vary intensity. Since the duration of sonication in the in vivo protocol is only 0.2 s per trial, the temperature effect (~0.1C after ~240 s of continuous sonication in a phantom) should be negligible.
Flags from extraction
n_subjects— Text explicitly gives 'four mice' for the main intensity-response experiment, but additional single-mouse control experiments (0V AC, 0V DC, flipped device) and the separate freely-moving-mouse demonstration may or may not overlap with these four animals; total unique subjects across all experiments is unclear.anaesthesia— The paper contrasts prior work using anesthetized, head-fixed animals with its own acute and awake freely-moving experiments, but never explicitly states whether the acute (head-fixed) mouse experiments were performed under anesthesia.exposures[0].unspecified_domain.ispta_w_cm2— Intensity values (55.4 mW/cm2 at the described 80V driving condition; 34.1 mW/cm2 at which success rate exceeded 70%) are not stated as free-field or in-situ; domain is unspecified. Figure 2 caption labels the varied intensity as ISPPA while the text calls the same quantity ISPTA, a text/figure inconsistency.sham_type— Three control conditions are described (0V AC with 100V DC; 0V DC with 80V AC; device flipped/aimed away); classified overall as inactive_transducer, with the flipped-device condition also serving as an auditory (buzzing sound) sham.