Assessment of Neuroprotective Effects of Low-Intensity Transcranial Ultrasound Stimulation in a Parkinson’s Disease Rat Model by Fractional Anisotropy and Relaxation Time T2∗ Value
Yanchao Dong, Defeng Liu, Yuemei Zhao, Yi Yuan, Wenxi Wang, Shuo Wu, Xin Liang, Zhanqiu Wang, Lanxiang Liu
Frontiers in Neuroscience 2021 · 10.3389/fnins.2021.590354
Abstract
Background: Low-intensity transcranial ultrasound (LITUS) may have a therapeutic effect on Parkinson's disease (PD) patients to some extent. Fractional anisotropy (FA) and relaxation time T2 ∗ that indicate the integrity of fiber tracts and iron concentrations in brain tissue have been used to evaluate the therapeutic effects of LITUS. Purpose: This study aims to use FA and T2 ∗ values to evaluate the therapeutic effects of LITUS in a PD rat model. Materials and Methods: Twenty Sprague-Dawley rats were randomly divided into a hemi-PD group ( n = 10) and a LITUS group ( n = 10). Single-shot spin echo echo-planar imaging and fast low-angle shot T2WI sequences at 3.0 T were used. The FA and T2 ∗ values on the right side of the substantia nigra (SN) pars compacta were measured to evaluate the therapeutic effect of LITUS in the rats. Results: One week after PD-like signs were induced in the rats, the FA value in the LITUS group was significantly larger compared with the PD group (0.214 ± 0.027 vs. 0.340 ± 0.032, t = 2.864, P = 0.011). At the 5th and 6th weeks, the FA values in the LITUS group were significantly smaller compared with the PD group (5th week: 0.290 ± 0.037 vs. 0.405 ± 0.027, t = 2.385, P = 0.030; 6th week: 0.299 ± 0.021 vs. 0.525 ± 0.028, t = 6.620, P ∗ values in the injected right SN of the LITUS group were significantly higher compared with the PD group (5th week, 12.169 ± 0.826 in the LITUS group vs. 7.550 ± 0.824 in the PD group; 6th week, 11.749 ± 0.615 in the LITUS group vs. 7.550 ± 0.849 in the PD group). Conclusion: LITUS had neuroprotective effects and can reduce the damage of 6-OHDA-induced neurotoxicity in hemi-PD rats. The combination of FA and T2 ∗ assessments can potentially serve as a new and effective method to evaluate the therapeutic effects of LITUS.
Abstract via europepmc.
Exposures
Exposure 1: LITUS (unfocused) over the 6-OHDA lesioned side
Target: substantia nigra — “The stimulation site was the same side of the brain as the drug injection site.”
Device: other named manufacturer · Dukang Medical Devices, Co., Ltd. · DK-102T ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| 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 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) | 2.6 | ✓✓✓⚑ |
Total stimulation duration was 10 min with a total of 200 trials; the stimulation duration (SD) and tone-burst duration (TBD) were 400 and 0.5 ms at PRF 1 kHz. Stimulation was applied daily after the surgical procedure.
Flags from extraction
n_subjects— 20 rats were all lesioned; 10 received LITUS (the other 10 were the untreated hemi-PD group). Count of exposed animals given.exposures[0].timing.sonication_duration_s— 400 ms 'stimulation duration' taken as the train length; converted to 0.4 s.exposures[0].timing.duty_cycle_pct— Duty cycle not stated; not computed.exposures[0].target.terms— Target inferred from stimulation on the same side as the right SN injection; the transducer is unfocused (3.5 cm2) so the target is imprecise.exposures[0].unspecified_domain.isppa_w_cm2— Isppa measured with hydrophone but medium and skull path not stated; MinerU garbled the number in the text (2.6).anaesthesia— Anaesthesia stated for surgery and MRI; not stated for the sonication sessions.blinding— Only the MRI radiologists are stated as blinded.