Research Report: Feasibility Study of Intracranial Focused Ultrasound Ablation under Ultrasonic Guidance through Polyolefin-Based Cranial Implants

Academic Background

Histotripsy is a non-thermal, non-invasive cancer tumor ablation technology. When applied intracranially, it is limited by the skull’s significant absorption and reflection of ultrasound waves, requiring large and complex transducer arrays to overcome this issue. To address this bottleneck, a polyolefin-based biocompatible cranial repair material has been developed to reduce distortion of ultrasound waves when entering the intracranial space. However, the feasibility of this method for high-intensity focused ultrasound treatment (such as Histotripsy) has not been fully validated.

Source and Author Information

This research was authored by Lauren Ruger, Maya Langman, Renata Farrell, John H. Rossmeisl, Francesco Prada, and Eli Vlaisavljevich, all of whom are affiliated with Virginia Polytechnic Institute and State University and other related research institutions. The paper has been accepted by IEEE Transactions on Biomedical Engineering and will be officially published in 2024.

Research Process

Study Design

The study consists of three main components: first, measuring the effects of single-element transducers on the cranial repair material at different frequencies and angles; then, expanding to multi-element transducer arrays to determine pressure loss and focus distortion effects under clinically relevant test conditions; finally, verifying the ability to generate cavitation clouds in water and tissue-mimicking gels via optical imaging and conducting ablation experiments using red blood cell mimics and pig brain tissues.

Experiments with Single-Element Transducers

Customized single-element transducers of 500 kHz, 1 MHz, and 3 MHz were used to measure pressure waveforms. The single-element transducers were tested at angles of 90°, 120°, and 135° to simulate the conditions of multi-element transducer arrays in clinical use. Results showed that pressure loss increased with frequency and angle, and the measured sound propagation velocities under different conditions were 2472 m/s, 2234 m/s, and 2082 m/s, respectively.

Experiments with Multi-Element Transducer Arrays

Using 8-element and 16-element multi-element transducer arrays, “simulated skull” experiments recorded significant transmission distortion affecting the focus position of the transducers under all conditions. By applying hydrophone-based distortion correction techniques, some of the lost pressure was recovered, reaching a maximum of 22 MPa.

Experimental Subjects and Equipment Inputs

All experiments used 4 mm thick polyolefin-based cranial repair materials. Instruments used included custom high-pressure pulse generators, micron-level precision 3D robotic positioning systems, and various types of ultrasound transducers.

Optical and Red Blood Cell Simulation Experiments

Using high-frequency optical imaging and red blood cell simulation experiments, it was found that even with the cranial repair material, Histotripsy cavitation clouds could still be generated in water and simulation gels, though the formation process was slower compared to free-field conditions. In the red blood cell virtual samples, despite significant pressure attenuation, effective ablation could still be achieved under high-frequency conditions.

Experiments with Pig Brain Tissues

Using pig brains obtained from local slaughterhouses embedded in degassed gelatin for the experiments, ultrasound imaging revealed clear generation of cavitation clouds, and the tissue was completely fragmented with no cellular structure.

Main Results

The experimental results of this study demonstrate that polyolefin-based cranial repair materials can serve as an acoustic window, making the application of Histotripsy within the skull possible. Despite significant pressure attenuation, by applying hydrophone-based distortion correction techniques, some of the lost pressure was recovered, and effective ablation was achieved under various simulated biological conditions.

Conclusion and Significance

The results of this study provide a basis for further optimizing ultrasound-guided Histotripsy technology, especially in scenarios where resources are limited or MRI guidance is not available, offering potential for treating intracranial lesions. Future studies need to improve Histotripsy equipment or employ other technologies such as nanoparticle-mediated Histotripsy to increase pressure, enhance ablation efficiency, and conduct more in vivo studies to evaluate safety and clinical feasibility.

Highlights

1. Innovative Repair Material: For the first time, the application of polyolefin-based cranial repair material has been verified to be effective not only for ultrasound imaging but also for high-intensity focused ultrasound treatment.
2. Multi-Angle Pressure Loss Study: Highlighted pressure loss under different frequency and angle conditions, providing a basis for multi-element transducer design.
3. Hydrophone-Based Distortion Correction Technique: Partially recovered pressure loss, demonstrating a method for improving treatment effects in practical applications.

Other Valuable Information

The study was partially funded by the Focused Ultrasound Foundation and the American Kennel Club Canine Health Foundation. Some members of the research team are also collaborating with related companies, laying the foundation for equipment improvement and clinical application. Moreover, the distortion correction techniques and high-frequency pulse generation methods implemented in this research hold significant reference value for other ultrasound treatment technologies.