Holographic Ultrasound Modulates Neural Activity in a 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Mouse Model of Parkinson’s Disease
Hui Zhou, Fei Li, Zhengrong Lin, Long Meng, Dan Chen, Qingping Zhang, Lili Niu
Research 2024 · 10.34133/research.0516
Abstract
Ultrasound (US) has emerged as a noninvasive neurostimulation method for motor control in Parkinson's disease (PD). Previous in vivo US neuromodulation studies for PD were single-target stimulation. However, the motor symptoms of PD are linked with neural circuit dysfunction, and multi-target stimulation is conducted in clinical treatment for PD. Thus, in the present study, we achieved multi-target US stimulation using holographic lens transducer based on the Rayleigh-Sommerfeld diffraction integral and time-reversal methods. We demonstrated that holographic US stimulation of the bilateral dorsal striatum (DS) could improve the motor function in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. The holographic US wave (fundamental frequency: 3 MHz, pulse repetition frequency: 500 Hz, duty cycle: 20%, tone-burst duration: 0.4 ms, sonication duration: 1 s, interstimulus interval: 4 s, spatial-peak temporal-average intensity: 180 mw/cm 2 ) was delivered to the bilateral DS 20 min per day for consecutive 10 d after the last injection of MPTP. Immunohistochemical c-Fos staining demonstrated that holographic US significantly increased the c-Fos-positive neurons in the bilateral DS compared with the sham group ( P = 0.003). Moreover, our results suggested that holographic US stimulation of the bilateral DS ameliorated motor dysfunction ( P P P P = 0.001), β3-tubulin ( P P = 0.037), postsynaptic density ( P = 0.023)]. These data suggested that holographic US-induced acoustic radiation force has the potential to achieve multi-target neuromodulation and could serve as a reliable tool for the treatment of PD.
Abstract via europepmc.
Exposures
Exposure 1: Holographic US to bilateral dorsal striatum
Target: dorsal striatum — “bilateral dorsal striatum (DS)”
Device: custom-built · holographic lens transducer, PZT-8 ceramic (Siansonic) ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 3,000 | ✓✓✓ |
| Pulse duration (ms) | 0.4 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 500 | ✓✓✓ |
| Duty cycle (%) | 20pulse duration × PRF gives 20% | ✓✓✓ |
| Sonication duration (s) | 1 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | 0.18 | ✓✓✓⚑ |
3 MHz, PRF 500 Hz, DC 20%, tone-burst duration 0.4 ms, sonication duration 1 s, interstimulus interval 4 s; 30 min (c-Fos) or 20 min per day for 10 days (treatment).
Flags from extraction
n_subjects— Group sizes differ by experiment: US group n=5 (c-Fos) and n=14 (pole test); rotarod n=10; unilateral-stimulation group size not stated. Listed [5,14]; total not stated.n_sessions_per_subject— 10 daily sessions in the treatment experiment; the c-Fos experiment was a single session.exposures[0].in_situ.ispta_w_cm2— Ispta measured by hydrophone after passing the mouse skull; written 180 mW/cm2, converted to 0.18 W/cm2.exposures[0].timing.sonication_duration_s— Per-day session was 20 min (30 min for c-Fos); the paper states SD as 1 s with ISI 4 s.auditory_control— No auditory control during the experiment; PRF of 500 Hz chosen below mouse hearing range and prior deaf-mouse work cited.blinding— Double blinding stated only for cell counting of immunostaining.exposures[0].device.family— Maker not named; transducer assembled by the authors from PZT-8 ceramic.