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Reduced Apparent Diffusion Coefficient in Various Brain Areas following Low-Intensity Transcranial Ultrasound Stimulation

Yi Yuan, Yanchao Dong, Shuo Hu, Tao Zheng, Dan Du, Juan Du, Lanxiang Liu

Frontiers in Neuroscience 2017 · 10.3389/fnins.2017.00562

rodenthealthyother mri

Abstract

Diffusion of water molecules closely related to physiological and pathological information of brain tissue. Low-intensity transcranial ultrasound stimulation (TUS) has advantages of noninvasive, high spatial resolution and penetration depth. Previous studies have demonstrate that TUS can modulate neuronal activity and alter cortical hemodynamic. However, how TUS affect diffusion of water molecules remain unclear. In this paper, in order to evaluate the effect of low-intensity TUS on the diffusion of water molecules in brain tissue, diffusion-weighted magnetic resonance (MR) imaging was performed in 19 healthy Sprague-Dawley rats in sham surgery group (six rats) and TUS group (thirteen rats) Subsequently, rats were stimulated by low-intensity transcranial ultrasound for 5 min in TUS group. Finally, rats of sham surgery group and TUS group were imaged again by diffusion-weighted MR imaging. The apparent diffusion coefficient (ADC) was measured in caudate putamen region and middle brain motor-related region of each rat in sham surgery group and TUS group. Surgery-related and TUS-related changes were calculated using a statistical analysis. The mean ADC values of marked regions of six rats in sham surgery group were 0.743 ± 0.031 (pre-surgery) and 0.745 ± 0.029 (post-surgery). The mean ADC values of marked regions of 13 rats in TUS group were 0.749 ± 0.032 (pre-TUS) and 0.712 ± 0.033 (post-TUS) Compared to the pre-TUS values, the mean ADC values of the rats decreased 4.9% ( * P < 0.05) post-TUS. These results of this study demonstrate that low-intensity TUS can restrict the diffusion of water molecules in brain tissue.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects13 animals
Sessions per subject1
Randomisednot reported
Blindingnot reported
Sham / controlno treatment control
Auditory controlnot reported
Readout timingoffline
Anaesthesiaanaesthetised
Readoutsother mri — diffusion-weighted MRI, apparent diffusion coefficient
Direction of effectmixed or unclearMean ADC fell 4.9% after TUS in the TUS group (13 rats), significant in 6 of 8 ROIs; sham-surgery group (6 rats, no TUS) unchanged.
Adverse eventsnot reportedMaximum temperature rise estimated analytically at about 1e-4 degC; no tissue assessment reported.

Exposures

Exposure 1: Transcranial US to whole rat head, 800 kHz

Target: striatum, midbrain — “caudate putamen region and middle brain motor-related region”
Device: other named manufacturer · Dukang Medical Devices · DK-102T ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)800✓✓✓
Pulse duration (ms)10✓✓✓⚑
Pulse repetition frequency (Hz)not reported⚑
Duty cycle (%)not reported
Sonication duration (s)300✓✓✓
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)1.2✓✓✓⚑
Ispta, domain unspecified (W/cm²)0.12✓✓✓
Protocol, in the paper’s words

'The ultrasound duration and the interstimulus interval were 10 and 100 ms, respectively', applied for 5 min through the skull with an unfocused transducer 2 mm above the gel-coated skull. Whether 10 ms is the pulse or a train, and the PRF, are not stated.

Flags from extraction

  • exposures[0].timing.pulse_duration_ms — Burst rule unresolved: 'ultrasound duration 10 ms and interstimulus interval 100 ms'; no PRF or duty cycle stated. Left not_reported.
  • exposures[0].timing.pulse_repetition_frequency_hz — Not stated; a 100 ms interstimulus interval is mentioned but not converted.
  • exposures[0].unspecified_domain.isppa_w_cm2 — Intensity cited from Kim et al 2014 as approximately 1.2 W/cm2; medium not stated; Ispta 0.12 'calculated as previously reported'.
  • n_subjects — 19 rats in total, of which 13 received TUS and 6 were sham surgery; text elsewhere says n=6 for TUS pre/post means (inconsistent).
  • exposures[0].target — Unfocused transducer over the rat head; ADC measured in caudate putamen and midbrain motor-related ROIs, which are not strictly the sonication target.