Focused Ultrasound-mediated Non-invasive Brain Stimulation: Examination of Sonication Parameters
Hyungmin Kim, Alan Chiu, Stephanie D. Lee, Krisztina Fischer, Seung-Schik Yoo
Brain Stimulation 2014, 7, 748-756 · 10.1016/j.brs.2014.06.011
Abstract
Background Transcranial focused ultrasound (FUS) has emerged as a new brain stimulation modality. The range of sonication parameters for successful brain stimulation warrants further investigation. Objective The objective of this study was to examine the range of FUS sonication parameters that minimize the acoustic intensity/energy deposition while successfully stimulating the motor brain area in Sprague-Dawley rats. Methods We transcranially administered FUS to the somatomotor area of the rat brain and measured the acoustic intensity that caused excitatory effects with respect to different pulsing parameters (tone-burst duration, pulse-repetition frequency, duty cycle, and sonication duration) at 350 and 650 kHz of fundamental frequency. Results We observed that motor responses were elicited at minimum threshold acoustic intensities (4.9-5.6 W/cm(2) in spatial-peak pulse-average intensity; 2.5-2.8 W/cm(2) in spatial-peak temporal-average intensity) in a limited range of sonication parameters, i.e. 1-5 ms of tone-burst duration, 50% of duty cycle, and 300 ms of sonication duration, at 350 kHz fundamental frequency. We also found that the pulsed sonication elicited motor responses at lower acoustic intensities than its equivalent continuous sonication. Conclusion Our results suggest that the pulsed application of FUS selectively stimulates specific brain areas-of-interest at an acoustic intensity that is compatible with regulatory safety limits on biological tissue, thus allowing for potential applications in neurotherapeutics.
Abstract via europepmc.
Exposures
Exposure 1: Tail somatomotor cortex, 350 kHz, pulsed parameter sweep (TBD/DC/SD) and energy-matched continuous-wave comparison
Target: primary motor cortex — “somatomotor area of the brain that elicits tail movement (mid-line, 2 mm posterior to Bregma)”
Device: custom-built
| Waveform | pulsed, continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 350 | ✓✓✓ |
| Pulse duration (ms) | 0.25, 0.5, 1, 2, 3, 5swept | ✓✓✓ |
| Pulse repetition frequency (Hz) | 60, 100, 140, 150, 170, 230, 250, 300, 350, 500, 600, 700, 1,000, 1,200, 1,400, 2,000, 2,800swept | ✓✓✓ |
| Duty cycle (%) | 30, 50, 70, 100swept | ✓✓✓⚑ |
| Sonication duration (s) | 0.15, 0.2, 0.3, 0.4swept | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingmean or range across subjects | |
| In-situ pressure (kPa) | 420, 810swept | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 4.9, 5.6, 7.73, 22.4swept | ✓✓✓⚑ |
| In-situ Ispta (W/cm²) | 2.5, 2.8, 7.73, 11.2swept | ✓✓✓ |
Threshold acoustic intensities for eliciting tail movement were mapped at 350 kHz across combinations of tone-burst duration (0.25-5 ms), duty cycle (30/50/70%) and sonication duration (200/300/400 ms; fixed at 50% DC for the SD comparison), each stimulus given with an inter-stimulus interval of 2-3 s, success defined as sonication-synchronised tail movement on 5 consecutive stimuli. For comparison, a continuous-wave condition (100% duty cycle, 150 ms sonication duration, 350 kHz) was designed to deposit the same overall acoustic energy as the 50% DC/300 ms pulsed condition. The sequence of parameter sets was randomised and balanced across animals; repeated sessions on the same animal (different parameter sets, >=2 days apart) were allowed.
Exposure 2: Tail somatomotor cortex, 650 kHz, pulsed parameter sweep (fixed 50% DC/300 ms SD, varying TBD)
Target: primary motor cortex — “somatomotor area of the brain that elicits tail movement (mid-line, 2 mm posterior to Bregma)”
Device: custom-built
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 0.25, 0.5, 1, 2, 3, 5swept | ✓? |
| Pulse repetition frequency (Hz) | 100, 170, 250, 500, 1,000swept | ✓✓✓⚑ |
| Duty cycle (%) | 50 | ✓✓✓ |
| Sonication duration (s) | 0.3 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | derating | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | ⚑ |
| In-situ Ispta (W/cm²) | not reported |
Using 50% duty cycle and 300 ms sonication duration, threshold acoustic intensities were examined at 650 kHz across the same six tone-burst durations tested at 350 kHz, in a separate group of animals, to compare stimulation efficiency between the two fundamental frequencies; 350 kHz elicited responses at lower threshold intensities than 650 kHz for all tone-burst durations.
Flags from extraction
exposures[0].in_situ.isppa_w_cm2— Threshold intensities vary continuously with TBD/DC/SD (Table 1, Figs 3-4); only the headline optimal range (abstract), the stated 'effective' operating point, and the one high-intensity/adverse-event case are captured here rather than every combination tested.exposures[0].in_situ.pressure_kpa— Only two peak-pressure values are stated in the text (0.42 MPa for the effective parameters, 0.81 MPa for the high-intensity case that produced a histological finding); pressure is not given for other parameter combinations.exposures[0].timing.duty_cycle_pct— The continuous-wave comparison condition (100% duty cycle, 150 ms sonication duration) is described in protocol_description rather than added to these numeric lists, because it cannot be represented as a parallel array element alongside the pulsed TBD/PRF values without breaking the pulsed-only correspondence between those two fields.exposures[1].timing.pulse_repetition_frequency_hz— The source table's rows for 650 kHz at 0.25 and 0.5 ms tone-burst duration are corrupted/merged in text extraction (values bleed into adjacent rows); only the four legible PRF values (for 1, 2, 3 and 5 ms TBD) are included, though the main text states the full six-TBD range was tested at 650 kHz.exposures[1].in_situ.isppa_w_cm2— The paper states 350 kHz gave lower threshold intensities than 650 kHz across all TBDs but the specific 650 kHz threshold values are only shown in Fig. 5, not stated numerically in the main text.