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Readout-segmented echo-planar diffusion-weighted MR at 3.0 T for the evaluation the effect of low-intensity transcranial ultrasound on stroke in a rat model

Lanxiang Liu, Juan Du, Tao Zheng, Shuo Hu, Min Zhao, Xuemei Wang, Shuang Wu, Shuo Wu, Qinglei Shi

Magnetic Resonance Imaging 2020 · 10.1016/j.mri.2019.06.013

rodentstrokeother mrihistology molecular

Abstract

Objective To investigate the feasibility of the relative apparent diffusion coefficient (rADC) values based on readout-segmented echo-planar diffusion sequence in evaluation the effects of low-intensity transcranial ultrasound (LIPUS) on ischemic stroke in rat models at different onset times. Methods Sixty Sprague-Dawley rats (weight, 250 ± 10 g) were divided randomly into six groups (n = 10) to establish a permanent model of distal middle cerebral artery occlusion (dMCAO). The rats were stimulated with ultrasound for 10 min in the LIPUS groups at 0.5 h, 1 h, 3 h, 6 h, and 9 h after dMCAO (denoted as the LIPUS group (0.5 h), LIPUS group (1 h), LIPUS group (3 h), LIPUS group (6 h), LIPUS group (9 h), and Control group without ultrasound stimulation). Magnetic resonance imaging was acquired at 0.5 h and 1 h after dMCAO and then at 1-hour intervals until 12 h. The rADC values were then measured and calculated. The pathological results from the rat brains were obtained after the experiment. Results When LIPUS was applied 0.5 h after dMCAO, the rate of decline of rADC values in the early stages were significantly reduced and the final rADC values were significantly increased. When LIPUS were applied at 1 h, 3 h, and 6 h, the final rADC values only increased slightly and did not prevent early declines. No significant difference of ultrasound stimulation at 9 h was found. Conclusion The rADC values demonstrated difference at different time points after dMCAO between with and without LIPUS groups.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects10, 10, 10, 10, 10swept animals
Sessions per subject1
Randomisedyes
Blindingsingle
Sham / controlno treatment control
Auditory controlnot reported
Readout timingoffline
Anaesthesiaanaesthetised
Readoutsother mri, histology molecular — readout-segmented EPI diffusion-weighted MRI, relative ADC; TTC, BDNF immunostaining, H&E and Nissl staining
Direction of effectnot assessedNeuroprotective outcome: LIPUS started 0.5 h after dMCAO reduced the early fall in rADC and raised final rADC and BDNF staining; 1, 3 and 6 h gave smaller effects and 9 h none. Neuronal excitation or inhibition was not assessed.
Adverse eventsnot reported

Exposures

Exposure 1: LIPUS after dMCAO (0.5, 1, 3, 6 or 9 h post-occlusion)

Target: other — “transcranial ultrasound (target not stated)”
Device: other named manufacturer · Dukang Medical Devices, Co., Ltd. · DK-102T ✓

Pulse timing
Waveformpulsed
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✓✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot 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✓✓✓⚑
Protocol, in the paper’s words

Total stimulation duration 10 min with 200 trials; each trial a 400 ms stimulation (SD) of 0.5 ms tone bursts at a 1 kHz PRF. Unfocused transducer of 3.5 cm2 area. Stimulation delivered once, at 0.5, 1, 3, 6 or 9 h after dMCAO, depending on group.

Flags from extraction

  • n_subjects — Six groups of n=10; the Control group (10 rats) received no ultrasound, so exposed animals number 50. The stated total of 60 is recorded.
  • exposures[0].target — Paper never names the sonicated brain region; unfocused transducer on the shaved head, infarct in right cortex.
  • exposures[0].timing.pulse_duration_ms — Resolved the burst rule from the stated TBD of 0.5 ms (SD 400 ms is the stimulus train); duty cycle not stated.
  • exposures[0].unspecified_domain.isppa_w_cm2 — Isppa from a needle hydrophone; the paper does not say whether this is free field or through skull.
  • blinding — Only the MRI radiologists are stated to be blinded to group; no blinding of treatment delivery is described.
  • readout_timing — MRI at 0.5 h, 1 h then hourly to 12 h after dMCAO; timing relative to sonication not described precisely.