Enhanced neuronal activity in mouse motor cortex with microbubbles’ oscillations by transcranial focused ultrasound stimulation
Zhiwei Cui, Dapeng Li, Yang Feng, Tianqi Xu, Shan Wu, Yibao Li, Ayache Bouakaz, Mingxi Wan, Siyuan Zhang
Ultrasonics Sonochemistry 2019 · 10.1016/j.ultsonch.2019.104745
Abstract
Microbubbles (MBs) are known to serve as an amplifier of the mechanical effects of ultrasound, which combined with ultrasound are widely used in brain. The goal of this study is to investigate the effect of oscillating MBs on the neuronal activity in the central nervous system (CNS) of mammals. The motor cortex of mice brain was subjected to ultrasound stimulation with and without MBs, and evoked electromyogram signals were recorded. A c-fos immunofluorescence assay was performed to evaluate the neuronal activation in the region of ultrasound stimulation. BBB integrity during ultrasound stimulation with MBs was assessed in this study. Moreover, the safety of ultrasound stimulation with MBs was examined. Using ultrasound at 620 kHz, the injection of MBs significantly increased the success rate of motor response from 0.065 ± 0.06 to 0.28 ± 0.10 when stimulation was applied at 0.12 MPa and from 0.38 ± 0.09 to 0.77 ± 0.18 at 0.25 MPa (p + cells were significantly increased from 15.67 ± 3.51 to 53.01 ± 9.54 at 0.12 MPa acoustic pressure. At 0.25 MPa, the mean density of c-fos + cells was 81 ± 10.97 without MBs and it significantly increased to 124.12 ± 25.71 with MBs (p < 0.05). Enhanced neuronal activities were observed with 0.12 MPa ultrasound stimulation with MBs, while the integrity of BBB was not compromised, but 0.25 MPa ultrasound stimulation with MBs resulted in BBB disruption. These findings reveal that the oscillations of MBs can enhance neuronal activity in the CNS of mammals, and may provide an insight into the application of MBs combined with ultrasound in brain.
Abstract via europepmc.
Exposures
Exposure 1: 0.12 and 0.25 MPa, with and without microbubbles
Target: primary motor cortex — “motor cortex of the mouse”
Device: custom-built · custom 620 kHz frequency FUS transducer ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 620 | ✓✓✓ |
| Pulse duration (ms) | 2 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 250 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 50% | ⚑ |
| Sonication duration (s) | 0.4 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reportedsingle value | |
| In-situ pressure (kPa) | 120, 250swept | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 0.48, 2.11swept | ✓✓✓⚑ |
| In-situ Ispta (W/cm²) | not reported |
Pulses of 2 ms duration at 250 Hz PRF, total sonication 400 ms; twenty stimulations at 8 s intervals per condition. For c-fos and histology the motor cortex was stimulated for 30 min in 8 s intervals, with microbubbles injected every 10 min.
Flags from extraction
exposures[0].in_situ.pressure_kpa— Paper says values are peak rarefactional pressures at the focus after mouse skull attenuation, but not how obtained (hydrophone in water is also mentioned); method left not_reported.exposures[0].in_situ.isppa_w_cm2— Isppa described as equivalent; domain assumed same as the pressures from the preceding sentence.n_subjects— 10 mice per group for EMG; 3 per group for histology/BBB; total across experiments not stated.exposures[0].device.family— Transducer called custom; maker not named; classed custom_built.exposures[0].timing.duty_cycle_pct— Duty cycle not stated.