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Multifunctional Fiber‐Based Optoacoustic Emitter as a Bidirectional Brain Interface

Nan Zheng, Ying Jiang, Shan Jiang, Jongwoon Kim, Guo Chen, Yueming Li, Ji‐Xin Cheng, Xiaoting Jia, Chen Yang

Advanced Healthcare Materials 2023 · 10.1002/adhm.202300430

in vitro cellrodenthealthycellular imaginginvasive electrophysiologyhistology molecular

Abstract

A bidirectional brain interface with both "write" and "read" functions can be an important tool for fundamental studies and potential clinical treatments for neurological diseases. Herein, a miniaturized multifunctional fiber-based optoacoustic emitter (mFOE) is reported thatintegrates simultaneous optoacoustic stimulation for "write" and electrophysiology recording of neural circuits for "read". Because of the intrinsic ability of neurons to respond to acoustic wave, there is no requirement of the viral transfection. The orthogonality between optoacoustic waves and electrical field provides a solution to avoid the interference between electrical stimulation and recording. The stimulation function of the mFOE is first validated in cultured ratcortical neurons using calcium imaging. In vivo application of mFOE for successful simultaneous optoacoustic stimulation and electrical recording of brain activities is confirmed in mouse hippocampus in both acute and chronical applications up to 1 month. Minor brain tissue damage is confirmed after these applications. The capability of simultaneous neural stimulation and recording enabled by mFOE opens up new possibilities for the investigation of neural circuits and brings new insights into the study of ultrasound neurostimulation.

Abstract via europepmc.

Speciesrat (Sprague-Dawley); mouse (C57BL/6J)
Subjects5 animals
Sessions per subject4
Randomisednot reported
Blindingnot reported
Sham / controlinactive transducer
Auditory controlnot reported
Readout timingonline
Anaesthesiaanaesthetised
Readoutscellular imaging, invasive electrophysiology, histology molecular — Oregon Green BAPTA-1 calcium imaging; local field potential and spike recording through mFOE electrodes; NeuN, Iba1, GFAP immunohistochemistry
Direction of effectexcitatoryOptoacoustic bursts of 50 ms or longer evoked calcium transients in cultured neurons, and evoked LFP responses in mouse hippocampus; 5 ms bursts evoked none.
Adverse eventsnot reportedMechanical index of 2.3 MPa waves calculated as 0.2; surface temperature rise about 1 degC; histology compared foreign body response with a silica fiber.

Exposures

Exposure 1: Optoacoustic stimulation of cultured rat cortical neurons

Target: cultured neurons — “rat cortical neurons”
Device: custom-built · multifunctional fiber-based optoacoustic emitter (mFOE) ✓

Pulse timing
Waveformother patterned
Fundamental frequency (kHz)12,500✓✓✓⚑
Pulse duration (ms)0.00008✓✓✓⚑
Pulse repetition frequency (Hz)1,700✓✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 0.014%
Sonication duration (s)0.005, 0.05, 0.1, 0.2swept✓✓✓⚑
Pressure and intensity, by domain
Free-field pressure (kPa)2,300✓✓✓⚑
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

1030 nm, 3 ns laser pulses at 1.7 kHz delivered in bursts of 5, 50, 100 or 200 ms (41.8 uJ per pulse); 5 bursts at 1 s intervals in the reproducibility test. Acoustic pulse width about 0.08 us (single laser pulse); only 50 ms or longer evoked calcium responses.

Exposure 2: Optoacoustic stimulation of mouse hippocampus with implanted mFOE

Target: hippocampus — “hippocampus”
Device: custom-built · multifunctional fiber-based optoacoustic emitter (mFOE) ✓

Pulse timing
Waveformother patterned
Fundamental frequency (kHz)12,500✓✓✓
Pulse duration (ms)0.00008✓✓✓
Pulse repetition frequency (Hz)1,700✓✓✓
Duty cycle (%)not reportedpulse duration × PRF gives 0.014%
Sonication duration (s)0.05✓✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)2,300✓✓✓⚑
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

50 ms bursts of 1030 nm, 3 ns laser pulses (41.8 uJ, 1.7 kHz repetition rate) delivered at 1 Hz during a 5 second treatment period, at 3 days, 7 days, 2 weeks and 1 month after implantation.

Flags from extraction

  • exposures[0].fundamental_frequency_khz — Broadband optoacoustic pulse; 12.5 MHz is the stated peak of the spectrum, recorded as the frequency
  • exposures[0].free_field.pressure_kpa — Peak-to-peak pressure (2.3 MPa) measured by hydrophone in water at 41.8 uJ; 1.0 and 1.6 MPa at lower energies; not peak negative
  • exposures[1].free_field.pressure_kpa — Water measurement carried over by the paper's reported pulse energy (41.8 uJ), not measured in tissue
  • exposures[0].timing.pulse_duration_ms — Acoustic pulse width about 0.08 us given in us; laser pulse is 3 ns; duty cycle not stated
  • exposures[0].timing.sonication_duration_s — Burst durations 5, 50, 100, 200 ms swept
  • n_subjects — 5 mice implanted for stimulation; cultures counted as N = 15 stimulation events; separate mice for histology and controls
  • sham_type — Laser-only control with fiber lacking optoacoustic coating, plus a dead-brain control

Notes: Optoacoustic (fiber laser) rather than transducer ultrasound; two exposures by target.