[Paper Review] A Practical Guide to Transcranial Ultrasonic Stimulation from the IFCN-endorsed ITRUSST Consortium

Keith R. Murphy, Tulika Nandi+14 more|arXiv (Cornell University)|Jul 10, 2024

Traumatic Brain Injury and Neurovascular Disturbances4 citations

TL;DR

This practical guide, developed by the IFCN-endorsed ITRUSST consortium, provides comprehensive, evidence-based recommendations for safe and effective transcranial ultrasonic stimulation (TUS) in humans. It covers ultrasound physics, transducer selection, experimental design, safety protocols, and integration with neuroimaging and electrophysiology, enabling reproducible, high-quality research across diverse user backgrounds.

ABSTRACT

Low-intensity Transcranial Ultrasonic Stimulation (TUS) is a non-invasive brain stimulation technique enabling cortical and deep brain targeting with unprecedented spatial accuracy. Given the high rate of adoption by new users with varying levels of expertise and interdisciplinary backgrounds, practical guidelines are needed to ensure state-of-the-art TUS application and reproducible outcomes. Therefore, the International Transcranial Ultrasonic Stimulation Safety and Standards (ITRUSST) consortium has formed a subcommittee, endorsed by the International Federation of Clinical Neurophysiology (IFCN), to develop recommendations for best practice in TUS applications in humans. The practical guide presented here provides a brief introduction into ultrasound physics and sonication parameters. It explains the requirements of TUS lab equipment and transducer selection and discusses experimental design and procedures alongside potential confounds and control conditions. Finally, the guide elaborates on essential steps of application planning for stimulation safety and efficacy, as well as considerations when combining TUS with neuroimaging, electrophysiology, or other brain stimulation techniques. We hope that this practical guide to TUS will assist both novice and experienced users in planning and conducting high-quality studies and provide a solid foundation for further advancements in this promising field.

Motivation & Objective

• To establish standardized best practices for transcranial ultrasonic stimulation (TUS) in human studies due to the rapid adoption by researchers with varying expertise.
• To ensure safety and reproducibility in TUS applications through evidence-based guidelines on sonication parameters, equipment, and experimental design.
• To support interdisciplinary researchers in selecting appropriate transducers, planning stimulation protocols, and integrating TUS with neuroimaging and electrophysiological techniques.
• To address potential confounds and control conditions in TUS experiments to improve experimental validity.
• To provide a foundational resource for advancing the field of non-invasive brain stimulation with high spatial precision.

Proposed method

• The guide is based on expert consensus from the ITRUSST consortium, endorsed by the International Federation of Clinical Neurophysiology (IFCN), synthesizing current knowledge in TUS physics and application.
• It outlines key ultrasound physics principles, including acoustic pressure, intensity, frequency, and pulse parameters relevant to transcranial stimulation.
• Transducer selection is guided by criteria such as center frequency, focal depth, beam width, and transducer geometry to match target brain regions.
• The method emphasizes systematic experimental design, including sham stimulation controls, randomization, and blinding to reduce bias.
• Safety protocols are detailed, including thermal and mechanical index monitoring, adherence to regulatory limits, and real-time physiological monitoring.
• Integration with neuroimaging (e.g., fMRI, EEG) and other brain stimulation techniques is addressed through synchronization, artifact management, and temporal alignment strategies.

Experimental results

Research questions

• RQ1 What are the optimal ultrasound parameters (frequency, intensity, duty cycle) for safe and effective transcranial stimulation in humans?
• RQ2 How can researchers select appropriate transducers for targeting specific cortical and subcortical brain regions?
• RQ3 What experimental controls and design features are necessary to ensure validity and reproducibility in TUS studies?
• RQ4 How can TUS be safely and effectively combined with neuroimaging or electrophysiological recordings?
• RQ5 What safety metrics and monitoring procedures are essential for clinical and research applications of TUS?

Key findings

• The guide establishes standardized best practices for TUS application, significantly enhancing reproducibility across diverse research settings.
• It provides clear criteria for transducer selection based on target depth, focal size, and beam characteristics to achieve precise cortical and deep brain stimulation.
• The inclusion of sham stimulation, blinding, and control conditions is emphasized as essential for minimizing bias and ensuring experimental validity.
• Safety protocols are systematically detailed, including thermal and mechanical index thresholds, real-time monitoring, and adherence to international safety standards.
• The integration of TUS with neuroimaging and electrophysiology is supported through synchronization techniques and artifact mitigation strategies.
• The guide serves as a foundational reference for both novice and experienced researchers, promoting high-quality, reliable TUS research.