Focused Ultrasound-Induced Suppression of Auditory Evoked Potentials in Vivo
Dianne Daniels, Shirley Sharabi, David Last, David Guez, Sharona Salomon, Zion Zivli, David Castel, Alex Volovick, Javier Grinfeld, Itay Rachmilevich, Talia Amar, Sigal Liraz-Zaltsman, Narek Sargsyan, Yael Mardor, Sagi Harnof
Ultrasound in Medicine & Biology 2018 · 10.1016/j.ultrasmedbio.2018.01.010
Abstract
The goal of this study was to determine the feasibility of focused ultrasound-based neuromodulation affecting auditory evoked potentials (AEPs) in animals. Focused ultrasound-induced suppression of AEPs was performed in 22 rats and 5 pigs: Repetitive sounds were produced, and the induced AEPs were recorded before and repeatedly after FUS treatment of the auditory pathway. All treated animals exhibited a decrease in AEP amplitude post-treatment in contrast to animals undergoing the sham treatment. Suppression was weaker for rats treated at 2.3 W/cm2 (amplitudes decreased to 59.8 ± 3.3% of baseline) than rats treated at 4.6 W/cm2 (36.9 ± 7.5%, p <0.001). Amplitudes of the treated pigs decreased to 27.7 ± 5.9% of baseline. This effect lasted between 30 min and 1 mo in most treated animals. No evidence of heating during treatment or later brain damage/edema was observed. These results demonstrate the feasibility of inducing significant neuromodulation with non-thermal, non-invasive, reversible focused ultrasound. The long recovery times may have clinical implications.
Abstract via pubmed.
Exposures
Exposure 1: FUS to rat inferior colliculus (2.3 and 4.6 W/cm2 groups)
Target: inferior colliculus — “inferior colliculus region”
Device: Insightec · InSightec, Tirat Carmel, Israel · ExAblate4000 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 230 | ✓✓✓ |
| Pulse duration (ms) | 100 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 0.333 | ✓✓✓⚑ |
| Duty cycle (%) | 3pulse duration × PRF gives 3.33%, which disagrees with the stated value | ✓✓✓ |
| Sonication duration (s) | 52 | ✓✓✓ |
| 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) | 39.7, 79.3swept | ✓✓✓ |
| Isppa, domain unspecified (W/cm²) | 2.3, 4.6swept | ✓✓✓⚑ |
All treatment lasted 52 s, consisting of 100 ms on and 2900 ms off (~3% duty cycle). Rats were treated in the inferior colliculus region. Seven rats were treated at 2.3 W/cm2 and 15 rats at 4.6 W/cm2 (Isppa). Baseline AEPs were recorded prone, then animals were positioned supine in the MR-guided FUS system for treatment, followed by continuous EEG recording of AEPs for 30 min to ~2 h post-sonication and weekly follow-up recordings for up to 2 months.
Exposure 2: FUS to pig auditory cortex (4.6 W/cm2)
Target: auditory cortex — “auditory cortex region”
Device: Insightec · InSightec, Tirat Carmel, Israel · ExAblate4000 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 230 | ✓✓✓ |
| Pulse duration (ms) | 100 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 0.333 | ✓✓✓⚑ |
| Duty cycle (%) | 3pulse duration × PRF gives 3.33%, which disagrees with the stated value | ✓✓✓ |
| Sonication duration (s) | 52 | ✓✓✓ |
| 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 | |
| Isppa, domain unspecified (W/cm²) | 4.6 | ✓✓✓⚑ |
All treatment lasted 52 s, consisting of 100 ms on and 2900 ms off (~3% duty cycle). Pigs were treated in the auditory cortex region at 4.6 W/cm2, following bilateral frontal craniectomy (the FUS brain system was designed for a human skull, so pig treatment was invasive).
Flags from extraction
n_subjects— Abstract/methods state 22 rats and 5 pigs studied, but 7+15=22 rats matches only the two real-treatment groups; a separate statement says 'Three rats in the sham group underwent the same procedure without activation of FUS,' which is unclear whether these 3 are included in or additional to the 22. n_subjects=27 (22 treated rats + 5 pigs) counts only real-FUS-exposed animals; total enrolled (incl. sham) may be higher.exposures[0].unspecified_domain.isppa_w_cm2— Paper reports Isppa and acoustic pressure without stating whether these are free-field (water-tank) or in-situ (skull-corrected) values; placed in unspecified_domain.exposures[1].unspecified_domain.isppa_w_cm2— Same ambiguity as the rat exposure; additionally pigs underwent craniectomy (transducer applied without intervening skull), which may make this value closer to a no-skull/free-field condition, but the paper does not say so explicitly.exposures[0].timing.pulse_repetition_frequency_hz— PRF (0.333 Hz) computed as the reciprocal of the stated 100 ms on / 2900 ms off cycle period; the paper does not itself state a PRF value.exposures[1].timing.pulse_repetition_frequency_hz— Same derivation as exposure 0; the 52-s/100-ms/2900-ms description is given once for the whole FUS treatment protocol used for both species.