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Wearable Transcranial Ultrasound System for Remote Stimulation of Freely Moving Animal

Evgenii Kim, Eloise Anguluan, Jeungeun Kum, Jorge Sanchez-Casanova, Tae Young Park, Jae Gwan Kim, Hyungmin Kim

IEEE Transactions on Biomedical Engineering 2021, 68, 2195-2202 · 10.1109/tbme.2020.3038018

rodenthealthystrokecerebral haemodynamicsbehaviourhistology molecular

Abstract

Objective Transcranial focused ultrasound (tFUS) has drawn considerable attention in the neuroscience field as a noninvasive approach to modulate brain circuits. However, the conventional approach requires the use of anesthetized or immobilized animal models, which places considerable restrictions on behavior and affects treatment. Thus, this work presents a wireless, wearable system to achieve ultrasound brain stimulation in freely behaving animals. Methods The wearable tFUS system was developed based on a microcontroller and amplifier circuit. Brain activity induced by tFUS was monitored through cerebral hemodynamic changes using near-infrared spectroscopy. The system was also applied to stroke rehabilitation after temporal middle cerebral artery occlusion (tMCAO) in rats. Temperature calculations and histological results showed the safety of the application even with prolonged 40 min sonication. Results The output ultrasonic wave produced from a custom PZT transducer had a central frequency of 457 kHz and peak to peak pressure of 426 kPa. The device weight was 20 g, allowing a full range of motion. The stimulation was found to induce hemodynamic changes in the sonicated area, while open-field tests showed that ultrasound applied to the ipsilateral hemisphere for 5 consecutive days after the stroke facilitated recovery. Conclusion The wearable tFUS system has been designed and implemented on moving rats. The results showed the ability of device to cause both short- and long lasting effects. Significance The proposed device provides a more natural environment to investigate the effects of tFUS for behavioral and long-term studies.

Abstract via europepmc.

Speciesrat (Sprague-Dawley)
Subjects6, 5, 4swept animals
Sessions per subjectnot reported
Randomisedyes
Blindingnot reported
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingboth
Anaesthesiaawake
Readoutscerebral haemodynamics, behaviour, histology molecularNear-infrared spectroscopy (NIRS) of cerebral hemodynamics (HbO/RHb/THb); open-field test locomotor distance; TTC staining for neuronal death
Direction of effectmixed or unclearUltrasound stimulation of motor cortex produced a pronounced cerebral hemodynamic change, but the pattern differed across animals: half showed increased HbO/decreased RHb and half showed the reverse. Daily stimulation after stroke improved post-stroke locomotor recovery relative to sham and untreated groups.
Adverse eventsnone observedCalculated temperature increase due to ultrasound was not higher than 0.14C (skull) and 0.0018C (brain); TTC staining showed no neuronal death after prolonged (40 min) sonication.

Exposures

Exposure 1: tFUS stimulation of motor cortex (online hemodynamic and offline post-stroke recovery)

Target: motor cortex — “motor cortex
Device: custom-built · Steiner & Martins Inc. (PZT ceramic element) · SMD05T04R111 (PZT element)

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)457✓✓
Pulse duration (ms)not reportedimplied by duty cycle ÷ PRF: 0.5 ms (not stated by the paper)
Pulse repetition frequency (Hz)1,000✓✓
Duty cycle (%)50✓✓
Sonication duration (s)0.3✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)426✓✓
Free-field Isppa (W/cm²)1.6✓✓
Free-field Ispta (W/cm²)not reported
In-situ estimatemeasurement
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Protocol, in the paper’s words

Each ultrasound stimulation lasted for 300 ms and contained a pulse train with a pulse repetition frequency (PRF) of 1 kHz and a duty cycle (DC) of 50%. For the online hemodynamic study, a total of 10 stimulations at 2 Hz were delivered for each trial, and each animal underwent 50 trials during an experimental session with the start of each trial being 1 minute apart. For post-stroke recovery, the tFUS group received daily stimulations with interstimulus interval of 2 sec for 40 min within 5 days after the stroke.

Consistency checks: intensity pressure inconsistent free field.

Flags from extraction

  • n_subjectsPaper gives only per-group sizes (n=6 NIRS, n=5 tFUS-treated, n=5 sham, n=5 untreated, n=5 healthy, n=4 histology) and no combined total 'exposed to ultrasound'; recorded as a list of the three groups that received actual sonication (NIRS, tFUS-treated stroke, prolonged-sonication histology safety check).
  • device.modelThe assembled tFUS transducer is custom-built in-house (3D-printed housing/lens); the manufacturer/model given (Steiner & Martins Inc., SMD05T04R111) is for the PZT ceramic element only, not the complete transducer assembly.
  • exposures[0].in_situ.pressure_kpaPaper reports only percentage transmission through the skull (70% pressure, 50% intensity), not absolute in-situ pressure/intensity values; converting the percentage to an absolute value would require arithmetic, so left not_reported.
  • n_sessions_per_subjectTwo different protocols are described (single online session of 50 trials for NIRS; daily sessions for 5 days for stroke recovery); no single 'sessions per subject' count applies to both, so left not_reported.