Name: Video: Performing Transcranial Ultrasound Neuromodulation Experiment in Humans
Uploaded: 2024-06-28T14:35:00
Description: 83 Views. Performing Transcranial Ultrasound Neuromodulation Experiment in Humans

performing transcranial ultrasound neuromodulation experiment in humans

High-Precision TUS: Planning and Execution with Acoustic and Thermal Simulations

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 precision1,2. By contrast, transcranial ultrasound (TUS) is an emerging non-invasive technique capable of enhancing or suppressing neuronal activity3,4,5 and targeting cortical or subcortical structures at millimeter precision6,7. Animal models using rodents4,8,9, rabbits10, sheep5,11, swine6, and nonhuman primates7,12,13,14 have shown the efficacy and safety of TUS. Studies have demonstrated that targeting various brain regions can elicit limb movements8 in rats, somatosensory evoked potentials (SSEPs) in swine6, and changes in visuomotor activity12, cognitive, and motivational decision-making in nonhuman primates13 among other changes in behavior. In humans, TUS has been observed to change motor evoked potentials (MEPs)&#160;and performance on a reaction time task when targeting the primary motor cortex15,16 and altered performance on a tactile discrimination task and SSEPs when targeting the somatosensory cortex17 and sensory thalamus18. Histological analyses have revealed no gross or microscopic structural changes associated with TUS in swine6, sheep5,11, rabbits10, and nonhuman primates14, and no side effects have been seen that significantly differ from other non-invasive neurostimulation techniques19.
TUS uses pulsed low-intensity focused ultrasound at a frequency between 200 kHz and 700 kHz to produce a transient neuromodulatory effect. The typical spatial-peak pulse-average intensity (Isppa) in situ is 10 W/cm2 or less, with reported duty cycles (percentage of time when ultrasound is on) ranging from 0.5% to 70% in humans20,21,22,23,24. Although the mechanisms of TUS neuromodulation have been proposed to mainly involve mechanical agitation of lipid membranes leading to the opening of ion channels25,26,27, possible thermal and cavitation effects cannot be ignored. They are assessed through mechanical (MI) and thermal (TI) indices. The MI describes the predicted cavitation-related bioeffects that will occur with TUS, whereas the TI describes the potential temperature increase within tissues following ultrasound application28,29. Furthermore, changing the frequency and input intensity also causes the MI and TI to change. Higher frequencies have better spatial resolution and decrease the probability of mechanical bio-effects; however, they have stronger absorption in the tissue, which increases the potential for temperature rise28. Alternatively, lower frequencies at the same intensity increase the MI. Similarly, increasing the intensity tends to increase the magnitude of mechanical and thermal bio-effects30. It is, therefore, imperative that careful planning and simulation be performed before experimentation sessions for all TUS parameters that will be implemented.
Planning a TUS experiment requires the identification of the target and trajectory of interest and the performance of thermal and acoustic simulations. Simulations assist in optimizing mechanical effects and mitigating the thermal effects of TUS on tissues. They require understanding the prediction of skull heating, pressure amplitude of the ultrasound at the focal point, focal correction, and other heating within the skull and skin. Adequate simulation ensures the focal point will reach the target of interest and safety parameters for ultrasound use set out by the safety guidelines on biophysical safety as recommended by the International Transcranial Ultrasonic Stimulation Safety and Standards Consortium (ITRUSST)31, which are based on FDA and Health Canada recommendations, are followed. Recent studies have also highlighted an auditory confounding effect accompanied by TUS32,33,34 in animals and humans, whereby TUS stimulation can activate auditory pathways in the brain to elicit responses32,33,34. Transection of the auditory nerves32, removal of cochlear fluid32, or chemical deafness33 in rodents have been employed to diminish these effects in animals. In humans, administering an auditory tone through headphones has been used to effectively mask auditory noise from TUS, controlling for the TUS-induced auditory activity confound34. This highlights the need to control for auditory noise in sham stimulation conditions, which must be incorporated into protocol planning, design, and implementation.
Here, we present a guide on how to appropriately complete the preparation (step 1, step 2), planning (step 3), simulations (step 4), and TUS delivery (step 5) required to perform TUS neuromodulation experiment in humans.

Author Spotlight: Advancing Human Brain Modulation &#8211; Optimized Protocols for Transcranial Ultrasound Stimulation Experiments

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

Performing Transcranial Ultrasound Neuromodulation Experiment in Humans

performing-transcranial-ultrasound-neuromodulation-experiment

Research

JoVE Journal

Neuroscience

83 Views. Performing Transcranial Ultrasound Neuromodulation Experiment in Humans

Video: Performing Transcranial Ultrasound Neuromodulation Experiment in Humans

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.

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.

Transcranial ultrasound stimulation (TUS) is an emerging non-invasive neuromodulation technique capable of manipulating both cortical and subcortical ...