Pipeline for Planning and Execution of Transcranial Ultrasound Neuromodulation Experiments in Humans

Summary

Transcranial ultrasound stimulation (TUS) is an emerging non-invasive neuromodulation technique that requires careful planning of acoustic and thermal simulations. The methodology describes an image processing and ultrasound simulation pipeline for efficient, user-friendly, streamlined planning for human TUS experimentation.

Abstract

Transcranial ultrasound stimulation (TUS) is an emerging non-invasive neuromodulation technique capable of manipulating both cortical and subcortical structures with high precision. Conducting experiments involving humans necessitates careful planning of acoustic and thermal simulations. This planning is essential to adjust for bone interference with the ultrasound beam's shape and trajectory and to ensure TUS parameters meet safety requirements. T1- and T2-weighted, along with zero-time echo (ZTE) magnetic resonance imaging (MRI) scans with 1 mm isotropic resolution, are acquired (alternatively computed tomography x-ray (CT) scans) for skull reconstruction and simulations. Target and trajectory mapping are performed using a neuronavigational platform. SimNIBS is used for the initial segmentation of the skull, skin, and brain tissues. Simulation of TUS is carried over with the BabelBrain tool, which uses the ZTE scan to produce synthetic CT images of the skull to be converted into acoustic properties. We use a phased array ultrasound transducer with electrical steering capabilities. Z-steering is adjusted to ensure that the target depth is reached. Other transducer configurations are also supported in the planning tool. Thermal simulations are run to ensure temperature and mechanical index requirements are within the acoustic guidelines for TUS in human subjects as recommended by the FDA. During TUS delivery sessions, a mechanical arm assists in the movement of the transducer to the required location using a frameless stereotactic localization system.

Introduction

Commonly used non-invasive neurostimulation techniques include transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS). However, both have limited penetration depth and low precision^1,2. By contrast, transcranial ultrasound (TUS) is an emerging non-invasive technique capable of enhancing or suppressing neuronal activity^3,4,5 and targeting cortical or subcortical structures at millimeter precision^6,7. Animal models using roden....

Protocol

All methods involving the use of human subjects were performed in compliance with the Tri-Council Ethical Conduct for Research Involving Humans, and the protocol was approved by the Conjoint Health Research Ethics Board (CHREB) at the University of Calgary. All subjects provided informed written consent before participation. Human participants were required to be healthy, right-handed adults between ages 18 and 40 willing and able to complete a magnetic resonance imaging (MRI) scan. Exclusion criteria included family history of seizure, mood, or cardiovascular disorders, ear trauma, alcohol or drug dependency, use of prescription medications, metal implants including ....

Results

Figure 7 illustrates comparative session samples from one of our studies⁴², featuring two distinct participants employing specific ultrasound parameters (fundamental frequency of 250 kHz, sonication duration of 120 s, a pulse repetition frequency (PRF) of 100 Hz, a duty cycle of 10%, and an I_SPPA of 5 W/cm²). In this research, T1-, T2-w, and ZTE MRI scans with 1 mm isotropic resolution were obtained from neurologically healthy subjects. TMS target.......

Discussion

In this method, subject-specific simulations are performed to predict and assess possible thermal and mechanical effects resulting from TUS application to the brain. Data sets between participants must remain separate and carefully documented, as using an incorrect scan or data file will lead to inaccurate simulations. When numerous participant scans are collected, and planning is performed together, it is important to ensure proper labeling of images and folders and proceed with caution when sorting and saving files.

Materials

Name	Company	Catalog Number	Comments
128-channel amplifier unit	Image Guided Therapy		This unit drives the H-317 transducer
24-channel head coil	General Electric
3D printer	Raise3D	Pro2	Filament thickness of 1.75mm.
3T MRI scanner	General Electric	Discovery 750 HD	MR Console version DV26.0_R05_2008
BabelBrain	Samuel Pichardo (University of Calgary)	Version 0.3.0	Accessible at https://github.com/ProteusMRIgHIFU/BabelBrain. Executes thermal and acoustic simulations.
Blender	Blender Foundation	Version 3.4.1	Accessible at https://www.blender.org. Blender is called automatically by BabelBrain.
Brainsight	Rogue Research	Version 2.5.2	Used for target identification, trajectory planning, and execution of TUS delivery sessions.
Chair and chin/head holder	Rogue Research		To be used during TUS delivery session to ensure stability of participant’s head for optimized targeting.
Custom-made coupling cone	University of Calgary team		3D printed cone in acrylonitrile butadiene styrene (ABS), only required for H-317 transducer.
dcm2niix	Chris Rorden (University of South Carolina)	Version 1.0.20220720	Accessible at https://github.com/rordenlab/dcm2niix/releases. Used for pre-processing subject MR images.
Fiducials and headband or glasses	Brainsight, Rogue Research	ST-1325 (subject tracker), LCT-583 (large coil tracker)	Headband or glasses can be interchangeably used.
Headphones	Beats	Fit Pro True Wireless Earbuds	Wireless Bluetooth earbuds with disposable tips.
MacBookPro	Apple	M2 Max, 16”, 64GB RAM	Computer for completing trajectory planning and simulations
SimNIBS	Axel Thielscher (Technical University of Denmark)	Version 4.0.0	Accessible at https://simnibs.github.io/simnibs/build/html.index.html
Syringe(s)		10 mL, 60 mL	Used to add additional ultrasound gel to fill air pockets.
Transducer	Sonicconcepts	H-317	Other supported transducers include CTX_500 (NeuroFUS, Sonicconcepts), Single element, H-246 (Sonicconcepts), and Bsonix (Brainsonix)
Transducer film	Sonicconcepts	Polyurethane membrane	Interface between transducer and the subject
Ultrasound gel	Wavelength	Clear Ultrasound Gel	Coupling medium.
Windows Laptop	Acer	Aspire A717-71G, Intel Core i7-7700HQ, 16 GB RAM	System used to control 128-channel amplifier and generate sound through the headphones