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Evaluating the Therapeutic Effect of Low‐Intensity Transcranial Ultrasound on Traumatic Brain Injury With Diffusion Kurtosis Imaging

Tao Zheng, Yi Yuan, Haoxiang Yang, Juan Du, Shuo Wu, Yinglan Jin, Zhanqiu Wang, Defeng Liu, Qinglei Shi, Xiaohan Wang, Lanxiang Liu

Journal of Magnetic Resonance Imaging 2020 · 10.1002/jmri.27063

rodenttraumatic brain injuryother mrihistology molecularbehaviour

Abstract

Background Low-intensity transcranial ultrasound (LITUS) has a therapeutic effect on traumatic brain injury (TBI). Diffusion kurtosis imaging (DKI) might be able to evaluate the effect changes of injured brain microstructure. Purpose To evaluate the therapeutic effect of LITUS in a moderate TBI rat model with DKI parameters. Study type Prospective case-control animal study. Animal model Forty-five rats were randomly divided into sham control, TBI, and LITUS treatment groups (n = 15). Field strength/sequence Single-shot spin echo echo-planar imaging and fast T 2 WI sequences at 3.0T. Assessment DKI parameters were obtained on days 1, 7, 14, 21, 28, 35, and 42 after TBI. Statistical tests For the mean kurtosis (MK), axial kurtosis (Ka), and radial kurtosis (Kr) values, groups were compared using a two-way analysis of variance (ANOVA). Results LITUS inhibited TBI and caused MK values to increase significantly during the early stage (LITUS vs. TBI, day 7, adjusted P Data conclusion The DKI parameter, particularly the MK value, evaluates primary cortical injury as well as the secondary brain injury that could not be detected by conventional T 2 WI. Level of evidence 1 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2020;52:520-531.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects15 animals
Sessions per subject42
Randomisedyes
Blindingsingle
Sham / controlno treatment control
Auditory controlnot reported
Readout timingoffline
Anaesthesiaanaesthetised
Readoutsother mri, histology molecular, behaviour — diffusion kurtosis imaging (MK, Ka, Kr) at 3.0 T; BDNF immunostaining, H&E; neurological function score
Direction of effectnot assessedNeuroprotective outcome: daily LITUS after controlled cortical impact attenuated the early rise and late fall of DKI mean kurtosis in cortex and prevented the thalamic MK rise, and raised BDNF staining scores; neuronal excitation or inhibition was not assessed.
Adverse eventsnot reported

Exposures

Exposure 1: LITUS to the CCI injury area

Target: cerebral cortex — “the injury area of the rat brain”
Device: Olympus / Panametrics · Olympus · V301-SU ✓

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

Stimulation duration 400 ms, tone-burst duration 0.5 ms, PRF 1 kHz; one trial lasted 3 s and 200 trials were evenly distributed over a total of 10 min, once daily from day 1 to day 42 after TBI. Unfocused transducer with a 10 mm collimator.

Flags from extraction

  • n_subjects — Three groups of 15 (sham, TBI, LITUS); only the 15 LITUS rats were sonicated.
  • n_sessions_per_subject — Stated as daily from day 1 to day 42 (once a day for 6 weeks); 42 is read from the day range.
  • exposures[0].target — Paper says ultrasound was applied to the injury area (right parietal cortex, CCI site); no atlas region named. Thalamus was imaged but not targeted.
  • 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.
  • exposures[0].device.family — Transducer named as Olympus V301-SU; driven by Tektronix function generators and an ENI amplifier.