image processing and ultrasound simulation pipeline for human transcranial ultrasound neuromodulation experimentation

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 &amp;#8211; Optimized Protocols for Transcranial Ultrasound Stimulation Experiments

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

Our research aims to understand the details of transcranial ultrasound stimulation to cause measurable effects in humans, including parameter specifications and its ability to modulate deep brain structures. Our protocol streamlines the planning steps required to complete transcranial ultrasound stimulation experiments in humans. It is efficient, easy to use, and involves using open source accessible planning tools.Our recent findings have shed light on the effect of optimal parameter selection in transcranial ultrasound stimulation to achieve neuronal inhibition. This will help in developing and designing future experiments in humans, significantly contributing to our understanding and advancement of this technology.

Image Processing and Ultrasound Simulation Pipeline for Human Transcranial Ultrasound Neuromodulation Experimentation

After performing the high-resolution magnetic resonance imaging, convert T1 weighted, T2 weighted, and zero time echo DICOM scan files from DICOM to NIfTI format using the dcm2niix tool. Using SimNIBS Charm tool, execute co-registration and tissue mask extraction. Next, open Brainsight.Click on New Empty Project, and load the participant's T1 weighted NIfTI image. Click on the Reconstructions tab, then on the New Reconstruction dropdown menu. Click on Skin, followed by Compute Skin in the new window.Once complete, click on the Close button in the top left corner of the window. Within the Reconstructions tab, click on the New Reconstruction dropdown menu, followed by Full Brain Curvilinear. Now adjust the position of the green box on the sagittal, coronal, and transverse planes by dragging its edges to tightly surround the brain.Scroll through all the slices to ensure no tissue edges overlap. Click on Compute Curvilinear, and adjust the peel depth to four millimeters. Then click on the Landmarks tab on Brainsight, followed by Configure Landmarks.Place the crosshairs on the tip of the nose, and in the name field, label the landmark Nose. Then place the crosshairs between the eyes above the bridge of the nose, and label the landmark Nasion. Next, place the crosshairs on the left ear, and label the landmark L Ear.Then place the crosshairs on the right ear, and label the landmark R Ear. Afterward, click on the Targets tab, followed by Configure Targets. Place the crosshairs on the location of the desired target, and use the angle toggles on the right side of the screen to set the trajectory angle.Once the desired target and trajectory are selected, click on the new dropdown menu and choose Trajectory. To name the target, type into the text box next to name. Click on Export to export the target, and save it in the appropriate subject folder.Open BabelBrain, and select the required files for acoustic and thermal simulations. To select the text file previously exported from Brainsite, click on Select Trajectory, and choose the appropriate participant file. Click on select SimNIBS, to choose the SimNIBS file created earlier.Click on Select T1W, and choose the T1 weighted image produced and used previously for target and trajectory mapping. Now choose Real CT for CT scans, CTE for CTE scans, or no to use a simplified mask generated by the Charm tool. When using a CT or CTE image, click on the Coreg dropdown menu, followed by CT to MR.Click on Select, and choose the corresponding image from the appropriate participant file.Click Select Thermal Profile, and choose the thermal profile file that describes the experiment sonication parameters in terms of duration on, duration off, and duty cycle. Then click on the dropdown menu beside Transducer, and select the transducer used for experimentation. Click on the dropdown menu beside computing backend, and choose the computing backend of the computer running the simulations.Once all information is entered, click on Continue to complete the rest of the simulations. Now select the transducer's ultrasound frequency, and the appropriate points per wavelength. Click on Calculate Planning Mask.Inspect the image to ensure the bounds for the skin, skull, and brain were accurately recognized. For acoustic simulation, click on the Step 2 AC Sim tab to open. Adjust the distance from the cone to the focal spot by typing in the appropriate distance.To execute the simulation, click on the Calculate Fields button. Adjust the ZSteering value so the crosshairs are in the center of the focal point. Press the up or down arrows or manually enter the required value.Then click on Calculate Fields. For thermal simulation, click on the Step 3 Thermal Sim tab, then click on Calculate Thermal Fields.

image-processing-ultrasound-simulation-pipeline-for-human

Research

JoVE Journal

Neuroscience

43 조회수. 고해상도 자기 공명 이미징을 수행한 후 dcm2niix 도구를 사용하여 T1 가중, T2 가중 및 제로 타임 에코 DICOM 스캔 파일을 DICOM에서 NIfTI 형식으로 변환합니다. SimNIBS Charm 도구를 사용하여 공동 정합 및 조직 마스크 추출을 실행합니다. 다음으로 Brainsight를 엽니다.New Empty Project(새 빈 프로젝트)를 클릭하고 참가자의 T1 가중치 NIfTI 이미지를 로드합니다....