Injectable Ultrasonic Sensor for Wireless Monitoring of Intracranial Signals

Neurology Organic Polymeric Materials Materials Science Medicine Bioengineering Biophysics Medical Imaging Life Sciences Neurosurgery
Intracranial signals Wireless monitoring Ultrasonic sensor Bioresorbable hydrogel Multiparameter sensing

Design of Injectable Ultrasound Sensor

Wireless Injectable Ultrasound Sensor for Intracranial Signal Monitoring

Background Introduction

Direct and accurate monitoring of intracranial physiological conditions is extremely important for injury classification, prognosis assessment, and disease prevention. However, traditional wired clinical devices, such as percutaneous leads, although performing excellently in terms of data acquisition accuracy, have issues such as infection risk, limited patient mobility, and potential surgical complications during the removal process. Wireless implantable devices provide greater operational freedom, but face challenges in limited detection range, poor degradability, and miniaturization within the human body.

Paper Source

This paper is jointly written by researchers from multiple institutions including Huazhong University of Science and Technology, Nanyang Technological University, Singapore Agency for Science, Technology and Research, and Wuhan Tongji Medical College, and published in Volume 630 of the journal Nature on June 6, 2024. The main authors include Hanchuan Tang, Yueying Yang, Zhen Liu, Wenlong Li, Yipeng Zhang, etc.

Research Content

Animal Experiments

Research Process

The research team proposed and developed a new type of wireless injectable biodegradable metamaterial hydrogel (metagel) sensor for ultrasound monitoring of intracranial signals. The sensor is designed as a 2×2×2 mm^3 cubic structure, containing a biodegradable stimuli-responsive hydrogel and periodically arranged air columns, exhibiting a specific acoustic reflection spectrum. These sensors can be directly implanted into the intracranial region through a puncture needle, and in response to changes in the physiological environment, undergo micro-deformations, leading to a shift in the peak frequency of the reflected ultrasound wave, which can be wirelessly measured by an external ultrasound probe.

Experimental Steps

  1. Sensor Design and Fabrication:

    • The sensor contains a hydrogel matrix and periodically arranged air columns, forming a soft phononic crystal with a tunable acoustic reflection spectrum.
    • By monitoring the frequency shift of the transmitted and reflected ultrasound waves, changes in the intracranial environment, including pressure, temperature, pH, and flow rate, can be monitored.
    • After implantation, the hydrogel gradually degrades in the physiological environment, and experiments show that it can be completely degraded within 18 weeks.

  2. Computation and Simulation:

    • Finite element analysis was used to calculate the band gap of the hydrogel and simulate the changes in the band gap and acoustic reflection frequency of the sensor under different pressures and temperatures.

  3. In Vitro and Animal Experiments:

    • First, the measurement range and accuracy for pressure, temperature, pH, and flow rate were verified through in vitro experiments.
    • Specific tests were conducted to evaluate the sensor’s response under different environmental parameters, including adjusting the temperature, pH, and pressure of the devices and liquids.

  4. Biocompatibility and Degradation Experiments:

    • In vivo experiments were performed on rat and pig models, and the long-term performance, stability, biocompatibility, and degradation of the sensors were evaluated using microscopic imaging and scanning techniques.

Main Results

  1. In Vitro Experimental Data Analysis:

    • The sensor showed a resolution of 0.1 mmHg and a sensitivity of 5.7 kHz/mmHg within the pressure range of 0-70 mmHg.
    • Within the temperature range of 28-43 °C, the sensor had a resolution of 0.1 °C and a sensitivity of approximately 80 kHz/°C.
    • The pH variation test showed that the sensor had a sensitivity of 256.4 kHz/pH unit within the pH range of 8.0 to 2.0, and could detect small changes of 0.0012.

  2. Animal Experimental Data Analysis:

    • In the in vivo experiments on rats and pigs, the sensor could real-time monitor changes in intracranial pressure and temperature, and the measurements were consistent with traditional monitoring devices such as clinical ICP sensors under different experimental conditions.
    • Experiments showed that the sensor’s accuracy and sensitivity were superior to existing clinical standard devices.

  3. Long-term Stability and Biocompatibility:

    • After implantation into the rat cranium, the sensor exhibited a morphology compatible with soft tissues, without causing significant inflammatory reactions.
    • During the testing period (less than 24 days), the sensor demonstrated long-term stability, and the combined parameter measurements and result decoupling methods confirmed good anti-interference capability.
    • MRI images clearly showed the implantation site of the sensor in the brain without any significant artifacts.

Conclusion and Significance

The metagel ultrasound sensor proposed by the research team provides an innovative, fully wireless multi-parameter detection solution. Compared to existing wireless implantable sensors, the sensor described in this paper has significant advantages in terms of size, degradability, and multi-signal decoupling, without requiring additional surgical procedures for sensor removal. This research result is expected to drive the development of safe and miniaturized wireless implantable sensors, replacing the existing clinical sensor systems that require percutaneous leads, and providing new technical means for precise disease prevention, prognosis, and health management. Applications include real-time monitoring of intracranial pressure, temperature, pH, and flow rate, as well as future extensions to monitoring other physiological parameters.