Monitoring cerebral hemodynamic change during transcranial ultrasound stimulation using optical intrinsic signal imaging
Evgenii Kim, Eloise Anguluan, Jae Gwan Kim
Scientific Reports 2017, 7 · 10.1038/s41598-017-13572-0
Abstract
Transcranial ultrasound stimulation (tUS) is a promising non-invasive approach to modulate brain circuits. The application is gaining popularity, however the full effect of ultrasound stimulation is still unclear and further investigation is needed. This study aims to apply optical intrinsic signal imaging (OISI) for the first time, to simultaneously monitor the wide-field cerebral hemodynamic change during tUS on awake animal with high spatial and temporal resolution. Three stimulation paradigms were delivered using a single-element focused transducer operating at 425 kHz in pulsed mode having the same intensity (I SPPA = 1.84 W/cm 2 , I SPTA = 129 mW/cm 2 ) but varying pulse repetition frequencies (PRF). The results indicate a concurrent hemodynamic change occurring with all actual tUS but not under a sham stimulation. The stimulation initiated the increase of oxygenated hemoglobin (HbO) and decrease of deoxygenated hemoglobin (RHb). A statistically significant difference (p < 0.05) was found in the amplitude change of hemodynamics evoked by varying PRF. Moreover, the acoustic stimulation was able to trigger a global as well as local cerebral hemodynamic alteration in the mouse cortex. Thus, the implementation of OISI offers the possibility of directly investigating brain response in an awake animal during tUS through cerebral hemodynamic change.
Abstract via europepmc.
Exposures
Exposure 1: tUS of mouse cortex at three PRF/pulse-duration paradigms (matched Isppa/Ispta)
Target: cerebral cortex — “mouse cortex, directed towards the bregma to provide a full image of the cortical brain”
Device: Olympus / Panametrics · Olympus Corp. · V301-SU ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 425 | ✓✓✓ |
| Pulse duration (ms) | 0.188, 0.094, 0.047swept | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 375, 750, 1,500swept | ✓✓✓ |
| Duty cycle (%) | not reported | |
| Sonication duration (s) | 0.2 | ✓✓✓ |
| Free-field pressure (kPa) | 530 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 1.84 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 0.129 | ✓✓✓ |
| 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 |
The ultrasound delivered was a 425 kHz pulse-modulated signal containing 10 pulse trains given over a period of 5 seconds for each trial. Every stimulus is a pulse train lasting 200 ms with M pulses given at a rate determined by the pulse repetition frequency (PRF), with each pulse having N cycles (Table 1: PRF 375/750/1500 Hz, N cycles 80/40/20, M pulses 75/150/300). Each trial image acquisition lasts for a total of 17 s including 5 s of stimulation containing ten ultrasound pulse trains with a repetition rate of 2 Hz; the interval between the beginning of each trial was fixed to 1 minute. The experiment on awake animals consisted of 100 randomly shuffled trials (25 per paradigm, including sham).
Consistency checks: intensity pressure inconsistent free field.
Flags from extraction
exposures[0].timing.pulse_duration_ms— Pulse duration not stated directly in ms; computed from N cycles ÷ fundamental frequency (Table 1: N=80/40/20 cycles at 425 kHz), per the sanctioned cycles-per-pulse conversion.exposures[0].unspecified_domain— The paper does not state whether the reported Isppa/Ispta/pressure values were measured in water (free field) or in situ; classified as unspecified domain.exposures[0].timing— The protocol nests short pulses (intra-train PRF 375/750/1500 Hz) within 200 ms trains that repeat 10 times over 5 s at a 2 Hz train-repetition rate; the schema's single PRF/duty-cycle fields cannot represent both levels. pulse_duration_ms and pulse_repetition_frequency_hz refer to the intra-train pulsing; sonication_duration_s is set to the 200 ms train length per the paper's own definition of a pulse train.randomised— Randomisation described is of trial order/paradigm sequence within a single-arm, within-subject design (100 randomly shuffled trials), not allocation to separate treatment groups.