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A Portable Ultrasound System for Non-Invasive Ultrasonic Neuro-Stimulation

Weibao Qiu, Juan Zhou, Yan Chen, Min Su, Guofeng Li, Huixia Zhao, Xianyi Gu, De Meng, Congzhi Wang, Yang Xiao, Kwok Ho Lam, Jiyan Dai, Hairong Zheng

IEEE Transactions on Neural Systems and Rehabilitation Engineering 2017, 25, 2509-2515 · 10.1109/tnsre.2017.2765001

rodentex vivo tissuehealthyinvasive electrophysiologyemg mepbehaviour

Abstract

Fundamental insights into the function of the neural circuits often follows from the advances in methodologies and tools for neuroscience. Electrode- and optical- based stimulation methods have been used widely for neuro-modulation with high resolution. However, they are suffering from inherent invasive surgical procedure. Ultrasound has been proved as a promising technology for neuro-stimulation in a non-invasive manner. However, no portable ultrasound system has been developed particularly for neuro-stimulation. The utilities used currently are assembled by traditional functional generator, power amplifier, and general transducer, therefore, resulting in lack of flexibility. This paper presents a portable system to achieve ultrasonic neuro-stimulation to satisfy various studies. The system incorporated a high voltage waveform generator and a matching circuit that were optimized for neuro-stimulation. A new switching mode power amplifier was designed and fabricated. The noise generated by the power amplifier was reduced (about 30 dB), and the size and weight were smaller in contrast with commercial equipment. In addition, a miniaturized ultrasound transducer was fabricated using Pb(Mg 1/3 Nb 2/3 )O 3 -PbTiO 3 (PMN-PT) 1-3 composite single crystal for the improved ultrasonic performance. The spatial peak temporal average pressure was higher than 250 kPa in the range of 0.5-5 MHz. In vitro and in vivo studies were conducted to show the performance of the system.

Abstract via europepmc.

Speciesmouse (in vivo brain stimulation); rat (ex vivo retina)
Subjectsnot reported animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlnone
Auditory controlnot reported
Readout timingonline
Anaesthesianot reported
Readoutsinvasive electrophysiology, emg mep, behaviourMulti-electrode array (MEA) recording of retinal ganglion cell extracellular potentials; electromyography (EMG) from mouse tail muscle; video recording of tail motion response
Direction of effectexcitatoryUltrasound stimulation excited retinal ganglion cells (responses at stimulus onset and offset) and evoked tail-flick motor responses (via EMG and video) in mice, both indicating an activating effect.
Adverse eventsnot reported

Exposures

Exposure 1: In vivo mouse brain (tail motor area) stimulation

Target: brain — “The targeted region was located 4.0 mm anteroposteriorally and 3.5 mm laterally from the bregma
Device: Olympus / Panametrics · Olympus NDT · V314

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)1,000✓✓
Pulse duration (ms)not reported
Pulse repetition frequency (Hz)not reported
Duty cycle (%)not reported
Sonication duration (s)not reported
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
Protocol, in the paper’s words

The ultrasonic transducer was fixed on the mouse's head by a stereotaxic frame; ultrasonic gel was used for coupling and the target could be adjusted in three dimensions with a 0.01 mm step. The reaction of the mouse to brain stimulation (evoked by ultrasound stimulating bursts, 1 MHz transducer) was recorded by an EMG acquisition system from the tail muscle and by video; the tail flicked when the ultrasound stimulus was on and stayed still when off. Full acoustic timing and intensity parameters used for this in vivo demonstration are not stated; animal preparation and experimental details were referred to another publication.

Exposure 2: Ex vivo rat retina stimulation (MEA recording)

Target: retina — “isolated rat retina, retinal ganglion cells facing the electrode array
Device: not reported

Pulse timing
Waveformnot reported
Fundamental frequency (kHz)not reported
Pulse duration (ms)not reported
Pulse repetition frequency (Hz)not reported
Duty cycle (%)not reported
Sonication duration (s)not reported
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 applicable
In-situ pressure (kPa)not applicable
In-situ Isppa (W/cm²)not applicable
In-situ Ispta (W/cm²)not applicable
Protocol, in the paper’s words

Rat retinas were prepared and a small patch of retina was placed into a recording chamber with retinal ganglion cells facing a 120-electrode MEA, used to detect extracellular potentials. The transducer was placed right above the retina to achieve ultrasound stimulation, performed under dim red light. Recorded responses over 12 successive trials showed the retinal ganglion cell was reliably excited by both the onset and offset of each stimulus. The frequency, timing, and intensity parameters used for this ex vivo demonstration are not stated in the text.

Flags from extraction

  • exposures[0]Full acoustic timing (pulse duration, PRF, duty cycle, sonication duration) and intensity/pressure actually used for the in vivo mouse brain stimulation demonstration are not stated; the paper refers to methods described in another publication [Tufail et al., 2010]. General bench characterization of the same 1 MHz transducer (peak pressure 258 kPa in a separate water-tank scan, Fig. 8a) is not explicitly linked to this in vivo experiment, so it was not assigned here.
  • exposures[1]Neither the transducer/frequency (1 MHz commercial vs 3 MHz PMN-PT custom) nor any timing/intensity parameters are stated for the ex vivo retina stimulation experiment. The Discussion notes the miniaturized transducer 'would be useful for...MEA based physiological experiment', which may imply it was used, but this is not stated as fact in the Results.
  • n_subjectsThe paper reports single demonstrative examples (e.g., 'a mouse', 'a retinal ganglion cell (one channel)') without stating the total number of animals or retinal preparations used.
  • model_systemThis paper is primarily a device/engineering description with two brief, differently-scaled demonstration experiments (ex vivo rat retina via MEA, and in vivo mouse brain via EMG/video); top-level subject fields (n_subjects, subject_unit, anaesthesia, etc.) cannot fully represent both preparations simultaneously.